1 00:00:00,040 --> 00:00:03,720 Imagine for a moment that you're a detective, but you know you're 2 00:00:03,720 --> 00:00:06,360 not the kind you'd find in some noir novel. 3 00:00:06,360 --> 00:00:08,240 Right. No trench coat, no rainy St. 4 00:00:08,240 --> 00:00:09,320 corners. Exactly. 5 00:00:09,320 --> 00:00:11,480 You're not dusting a whiskey glass for fingerprints. 6 00:00:12,000 --> 00:00:15,120 Your your beat is much, much smaller than that. 7 00:00:15,480 --> 00:00:18,280 We're talking about a scale that is, I mean, it's literally 8 00:00:18,280 --> 00:00:20,240 invisible to the naked eye. It is. 9 00:00:20,240 --> 00:00:23,640 You're investigating A suspect that is infinitesimally small. 10 00:00:23,840 --> 00:00:25,800 You can't see it, you can't touch it. 11 00:00:25,920 --> 00:00:29,280 And you can't even, say freeze it to get a better look because 12 00:00:29,280 --> 00:00:32,400 that might fundamentally change its behavior, how it interacts 13 00:00:32,400 --> 00:00:35,440 with the world around it. But despite all of those 14 00:00:35,440 --> 00:00:39,560 limitations, you have a very specific, very demanding 15 00:00:39,560 --> 00:00:42,440 requirement. You need to know exactly what 16 00:00:42,440 --> 00:00:44,520 this suspect looks like. And we're not talking about a 17 00:00:44,520 --> 00:00:46,320 rough sketch here. We're not talking about a 18 00:00:46,320 --> 00:00:49,600 general idea of its shape. We need the architectural 19 00:00:49,600 --> 00:00:53,000 blueprints. Yes, you need the precise 3D 20 00:00:53,000 --> 00:00:55,200 structure. You need to know exactly how its 21 00:00:55,200 --> 00:00:57,560 skeleton is angled. You know, down to the degree. 22 00:00:57,560 --> 00:01:00,880 You need to know who its neighbors are, how tightly the 23 00:01:00,880 --> 00:01:02,560 bonds are holding it all together. 24 00:01:02,800 --> 00:01:05,760 And even how the electron cloud is shifting around it. 25 00:01:06,040 --> 00:01:09,040 So here's the question. If you can't see it or touch it 26 00:01:09,040 --> 00:01:11,880 or photograph it, how do you solve the case? 27 00:01:12,000 --> 00:01:13,560 How do you interrogate a molecule? 28 00:01:13,720 --> 00:01:15,840 Well, if you're a chemist, you don't pull out a magnifying 29 00:01:15,840 --> 00:01:19,400 glass, you pull out a magnet. A really, really, really big 30 00:01:19,400 --> 00:01:21,640 magnet. You essentially force it to talk 31 00:01:21,640 --> 00:01:24,320 to you using the laws of quantum physics. 32 00:01:24,960 --> 00:01:28,560 Welcome to the deep dive. Today, we are tackling one of 33 00:01:28,560 --> 00:01:31,080 the absolute Titans of modern science. 34 00:01:31,080 --> 00:01:33,160 A real heavy hitter in the analytical lab. 35 00:01:33,160 --> 00:01:36,320 We're doing a deep dive into NMR spectroscopy. 36 00:01:36,320 --> 00:01:41,000 Nuclear magnetic resonance. It is, and I don't think this is 37 00:01:41,000 --> 00:01:44,240 an overstatement, arguably the most powerful tool we have for 38 00:01:44,240 --> 00:01:46,680 figuring out the structure of molecules in detail. 39 00:01:46,720 --> 00:01:49,360 It's the closest thing we've ever invented to having, I don't 40 00:01:49,360 --> 00:01:51,280 know, X-ray vision for chemicals. 41 00:01:51,280 --> 00:01:53,880 That's a great way to put. It and we have a serious stack 42 00:01:53,880 --> 00:01:55,960 of research and lecture materials here today. 43 00:01:56,200 --> 00:01:59,880 We're working from a collection of notes that they really cover 44 00:01:59,880 --> 00:02:01,520 the full spectrum of this technology. 45 00:02:01,600 --> 00:02:03,360 They do. We've got materials on the 46 00:02:03,360 --> 00:02:06,200 fundamental principles. This is from a course on 47 00:02:06,200 --> 00:02:08,960 structure methods in inorganic chemistry. 48 00:02:09,199 --> 00:02:11,320 And then we have to really advanced stuff. 49 00:02:11,520 --> 00:02:14,800 The almost sci-fi world of solid-state NMR. 50 00:02:15,040 --> 00:02:18,200 And it really does get into sci-fi territory, especially 51 00:02:18,200 --> 00:02:21,040 when you start talking about the engineering that's required to 52 00:02:21,040 --> 00:02:24,000 make any of this work. So our mission today is to take 53 00:02:24,000 --> 00:02:26,000 you on that journey. We're going to start with the 54 00:02:26,000 --> 00:02:28,800 very basic physics of a spinning nucleus. 55 00:02:29,000 --> 00:02:31,760 What makes it tick? Why it even behaves like a 56 00:02:31,760 --> 00:02:33,280 little magnet in the first place. 57 00:02:33,400 --> 00:02:36,120 Then we'll get into the machine itself, which is just a beast of 58 00:02:36,120 --> 00:02:37,680 engineering. From there, we'll learn how to 59 00:02:37,680 --> 00:02:40,520 decode the secret messages these atoms sending us. 60 00:02:41,080 --> 00:02:43,680 And finally, we're going to build all the way up to a 61 00:02:43,680 --> 00:02:46,240 technique called Magic angle spinning. 62 00:02:46,280 --> 00:02:49,400 Which, I promise you, is every bit as cool as it sounds. 63 00:02:49,920 --> 00:02:52,120 I was hoping you'd say that. It's a technique where we 64 00:02:52,120 --> 00:02:56,560 literally spin a sample at, I mean thousands of mph just to 65 00:02:56,560 --> 00:02:58,800 trick the laws of physics. Or at least to cancel out the 66 00:02:58,800 --> 00:03:01,080 parts of physics that are, you know, being annoying. 67 00:03:01,080 --> 00:03:03,080 Exactly the parts that are getting in our way. 68 00:03:03,160 --> 00:03:06,680 So the mission is to understand how we go from a simple tube of 69 00:03:06,680 --> 00:03:10,840 clear liquid to a complex 3D map of reality. 70 00:03:11,840 --> 00:03:15,360 But before we get to the giant magnets and the magic angles, we 71 00:03:15,360 --> 00:03:17,360 have to start with the suspects themselves. 72 00:03:17,520 --> 00:03:21,400 Right, because it turns out not every atom is willing to 73 00:03:21,400 --> 00:03:23,440 cooperate with this kind of investigation. 74 00:03:23,440 --> 00:03:27,440 There's AVIP list. A very strict VIP list for who 75 00:03:27,440 --> 00:03:30,760 gets to participate in an NMR experiment. 76 00:03:30,760 --> 00:03:33,640 You can't just put any old substance in the machine and 77 00:03:33,640 --> 00:03:36,080 expect to get the signal. This was one of the first things 78 00:03:36,080 --> 00:03:37,520 in the reading that really surprised me. 79 00:03:37,520 --> 00:03:40,240 I sort of, I've assumed, you know, you put matter in a super 80 00:03:40,240 --> 00:03:42,280 strong magnet and something has to happen. 81 00:03:42,280 --> 00:03:44,240 You'd think so. But we're talking about a very 82 00:03:44,240 --> 00:03:46,320 specific property called nuclear spin. 83 00:03:46,640 --> 00:03:50,320 Now, when I hear spin, I'm thinking of a top, or, you know, 84 00:03:50,640 --> 00:03:54,160 a planet rotating on its axis. But this is quantum spin, right? 85 00:03:54,280 --> 00:03:56,240 It's different. Yes, and this is where our 86 00:03:56,240 --> 00:03:58,760 everyday intuition starts to fail us a little bit. 87 00:03:58,760 --> 00:04:01,840 When we say spin in quantum mechanics, we don't necessarily 88 00:04:01,840 --> 00:04:04,920 mean the nucleus is physically rotating like a basketball on 89 00:04:04,920 --> 00:04:07,480 your finger. It's an intrinsic property of 90 00:04:07,480 --> 00:04:10,120 the particle. It's a form of angular momentum. 91 00:04:10,120 --> 00:04:13,520 It's just something the particle has in the same way it has mass 92 00:04:13,520 --> 00:04:16,480 or it has charge. So it's like a fundamental tag 93 00:04:16,480 --> 00:04:17,880 that's just attached to it from the start. 94 00:04:17,880 --> 00:04:18,760 Exactly. Yeah. 95 00:04:18,920 --> 00:04:23,320 And for NMR to work, for nuclear magnetic resonance to happen at 96 00:04:23,320 --> 00:04:27,600 all, the nucleus has to have a spin that is not 00. 97 00:04:27,760 --> 00:04:29,800 We denote the spin with the letter I. 98 00:04:30,680 --> 00:04:33,680 If I equals 0, the nucleus is silent. 99 00:04:33,760 --> 00:04:36,400 It's invisible to the machine. It doesn't matter if you have a 100 00:04:36,400 --> 00:04:39,880 magnet the size of a planet, that nucleus will not talk to 101 00:04:39,880 --> 00:04:41,280 you. And looking at the source 102 00:04:41,280 --> 00:04:44,600 material, the rules for who has been and who doesn't are, 103 00:04:45,120 --> 00:04:47,120 they're surprisingly specific. They are. 104 00:04:47,240 --> 00:04:49,600 It feels a bit like a club bouncer checking IDs at the 105 00:04:49,600 --> 00:04:52,040 door. Oh, let me see your protons even 106 00:04:52,040 --> 00:04:53,440 number. Sorry you're not coming in 107 00:04:53,440 --> 00:04:55,000 tonight. That's a really good analogy. 108 00:04:55,000 --> 00:04:57,520 It is a lot like that, and the criteria are all about the 109 00:04:57,520 --> 00:05:00,200 composition of the nucleus, just the count of protons and the 110 00:05:00,200 --> 00:05:02,520 count of neutrons. OK, let's breakdown these rules 111 00:05:02,520 --> 00:05:05,080 because they dictate everything we can and cannot see in the 112 00:05:05,080 --> 00:05:09,800 molecular world. Rule #1 This covers what the 113 00:05:09,800 --> 00:05:13,280 notes call the Silent Majority. This is the big one. 114 00:05:14,000 --> 00:05:16,600 This is the rule that excludes a lot of the atoms we deal with 115 00:05:16,720 --> 00:05:18,800 every single day. The rule is simple. 116 00:05:19,400 --> 00:05:23,280 If an atom has an even number of protons, A&D and even number of 117 00:05:23,280 --> 00:05:29,200 neutrons, its netspin is 0. Equals 0 spin. 118 00:05:29,200 --> 00:05:31,160 Correct. On a quantum level, everything 119 00:05:31,160 --> 00:05:34,360 just pairs up and cancels out, and this is a huge deal because 120 00:05:34,360 --> 00:05:37,440 of who falls into this category. Just think about the most common 121 00:05:37,440 --> 00:05:40,000 elements in organic chemistry. Carbon and oxygen. 122 00:05:40,400 --> 00:05:43,560 The building blocks of life itself, specifically their most 123 00:05:43,560 --> 00:05:47,040 abundant isotopes, carbon 12 and oxygen 16. 124 00:05:47,040 --> 00:05:51,320 OK, so carbon 12, that's six proton, 6 neutrons even and 125 00:05:51,320 --> 00:05:54,480 even. Yep, and oxygen 16 is 8 protons 126 00:05:54,480 --> 00:05:56,600 and eight neutrons again, even and even. 127 00:05:56,600 --> 00:05:58,480 So wait, let's just pause on that for a second because that's 128 00:05:58,560 --> 00:06:00,400 that's kind of a big deal. Carbon 12 is what? 129 00:06:00,400 --> 00:06:02,040 Something like 99% of all carbon? 130 00:06:02,040 --> 00:06:06,360 About 98.9%, yeah. And oxygen 16 is 99.8% of all 131 00:06:06,360 --> 00:06:07,640 oxygen. And you're telling me they're 132 00:06:07,640 --> 00:06:09,400 completely invisible to this technique? 133 00:06:09,560 --> 00:06:12,760 In the context of NMR, yes. They don't have a magnetic 134 00:06:12,760 --> 00:06:14,960 moment. They are magnetically inert. 135 00:06:14,960 --> 00:06:17,080 You can put them in the biggest magnet on Earth and they just 136 00:06:17,760 --> 00:06:20,720 they won't interact. They are NMR silent. 137 00:06:21,360 --> 00:06:24,320 That is wild. So the bulk of organic matter, 138 00:06:24,320 --> 00:06:27,760 the very backbone of our bodies, the wood in this desk, the 139 00:06:27,760 --> 00:06:31,040 plastic in this microphone is basically dark matter to this 140 00:06:31,040 --> 00:06:32,320 machine. It's a ghost town. 141 00:06:32,320 --> 00:06:34,600 The machine sees right through. It it's there, but it can't be 142 00:06:34,600 --> 00:06:36,680 seen. So if the main building blocks 143 00:06:36,680 --> 00:06:40,200 are silent, who can we talk to? Who actually gets past the 144 00:06:40,200 --> 00:06:41,960 bouncer? We need the oddballs. 145 00:06:42,320 --> 00:06:44,160 That brings us to rule #2 in the notes. 146 00:06:44,200 --> 00:06:49,240 OK, the rule is if the mass number of the atom is odd, you 147 00:06:49,240 --> 00:06:53,000 get 1/2 integer spin, so something like 123252 and so on. 148 00:06:53,080 --> 00:06:55,400 And this is the sweet spot. This is the sweet spot for NMR. 149 00:06:55,400 --> 00:06:56,800 This is where all the action is which. 150 00:06:56,800 --> 00:06:58,960 Brings us to the real celebrities of the NMR world. 151 00:06:59,120 --> 00:07:01,320 Absolutely. And the biggest celebrity, the 152 00:07:01,320 --> 00:07:04,480 absolute A Lister that shows up in almost every chemistry paper 153 00:07:04,480 --> 00:07:07,360 you'll ever read, is the proton hydrogen one. 154 00:07:07,360 --> 00:07:10,640 Just a single proton. One proton, 0 neutrons. 155 00:07:11,120 --> 00:07:14,600 Its mass number is 1, which is odd, so its spin is 12. 156 00:07:14,960 --> 00:07:17,480 And it's perfect for this. It's perfect, it's incredibly 157 00:07:17,480 --> 00:07:20,360 sensitive, and just as importantly, it is everywhere. 158 00:07:20,360 --> 00:07:24,520 It makes up 99.98% of all hydrogen in the universe. 159 00:07:24,760 --> 00:07:28,160 So when people in the lab say I'm going to go run an NMR, 9 160 00:07:28,160 --> 00:07:30,560 times out of 10 they're not looking at the carbon skeleton 161 00:07:30,560 --> 00:07:33,760 directly, they're actually listening to the hydrogen atoms 162 00:07:33,920 --> 00:07:36,760 gossiping about their neighbors. Most of the time, yes, that's 163 00:07:36,760 --> 00:07:39,600 proton NMR. It's the standard because it's 164 00:07:39,600 --> 00:07:43,120 fast, it's sensitive, and the data is usually really clear. 165 00:07:43,240 --> 00:07:45,600 But. We can look at carbon, right? 166 00:07:45,760 --> 00:07:46,920 We just have to be clever about it. 167 00:07:46,960 --> 00:07:48,520 We can. We have to be clever. 168 00:07:48,600 --> 00:07:52,160 Remember, carbon 12 is silent, but there's another isotope, 169 00:07:52,240 --> 00:07:54,800 Carbon 13. Carbon 13. 170 00:07:55,040 --> 00:07:57,120 It has 6 protons but seven neutrons. 171 00:07:57,120 --> 00:08:01,760 Exactly that one extra neutron brings the mass number up to 13, 172 00:08:01,920 --> 00:08:05,920 which is an odd number spin. It has a spin of 12 and suddenly 173 00:08:05,920 --> 00:08:07,720 it's active. It has a magnetic voice. 174 00:08:07,720 --> 00:08:09,720 We can hear it. But there's a catch with carbon 175 00:08:09,720 --> 00:08:11,840 13, isn't there? It's not as easy as hydrogen. 176 00:08:11,840 --> 00:08:14,160 There's a big catch. It all comes down to abundance. 177 00:08:14,400 --> 00:08:18,360 Carbon 13 is only about 1.1% of all the carbon found in nature. 178 00:08:18,480 --> 00:08:23,560 So if I have a sample of say, sugar, only one out of every 100 179 00:08:23,560 --> 00:08:26,680 carbon atoms is actually talking to the machine. 180 00:08:26,880 --> 00:08:30,560 That's right, the other 99 are the silent carbon twelves. 181 00:08:30,560 --> 00:08:33,640 They're just along for the ride. Which must mean the signal is 182 00:08:33,640 --> 00:08:36,039 much, much weaker. Significantly weaker. 183 00:08:36,280 --> 00:08:40,720 You're trying to hear a whisper in a crowded, noisy room, and 184 00:08:40,720 --> 00:08:44,480 that explains why a Carbon NMR experiment takes so much much 185 00:08:44,480 --> 00:08:47,520 longer to run than a Proton NMR. You have to listen for a much 186 00:08:47,520 --> 00:08:49,520 longer time. A much longer time, sometimes 187 00:08:49,520 --> 00:08:52,120 hours or even overnight, just to collect enough data to 188 00:08:52,120 --> 00:08:54,280 distinguish the signal from the background noise. 189 00:08:54,400 --> 00:08:57,120 And just for completeness, there is a third rule in the notes. 190 00:08:57,120 --> 00:09:00,600 What about the integers? Right rule #3 This is if you 191 00:09:00,600 --> 00:09:04,160 have an odd number of protons and a an odd number of neutrons. 192 00:09:04,360 --> 00:09:06,760 Odd plus odd. In that case you get an integer 193 00:09:06,760 --> 00:09:10,880 spin like one or two or three. Examples here would be something 194 00:09:10,880 --> 00:09:14,040 like nitrogen 14 or deuterium which is hydrogen 2. 195 00:09:14,360 --> 00:09:16,000 Are active too. They are active. 196 00:09:16,000 --> 00:09:18,280 They do have spin, but they're much, much harder to work with. 197 00:09:18,280 --> 00:09:20,520 They have a property called a quadrupole moment. 198 00:09:20,720 --> 00:09:22,840 A quadrupole. OK, it just means their 199 00:09:22,840 --> 00:09:25,560 electrical charge isn't distributed in a perfect sphere. 200 00:09:25,560 --> 00:09:28,760 It's more like a football, and this makes their signals really 201 00:09:28,760 --> 00:09:30,840 broad and often difficult to interpret. 202 00:09:31,040 --> 00:09:34,360 We generally try to avoid them unless we really really need 203 00:09:34,360 --> 00:09:37,520 them for a specific problem. OK, so we've got our VIP list. 204 00:09:37,520 --> 00:09:40,200 We have our protons and our carbon thirteens. 205 00:09:40,200 --> 00:09:43,120 They have spin, they're in the club now. 206 00:09:43,200 --> 00:09:45,360 We take these atoms and we put them in the machine. 207 00:09:45,800 --> 00:09:48,680 This brings us to a concept in the notes called the Zeeman 208 00:09:48,680 --> 00:09:50,400 Effect. The Zeeman effect. 209 00:09:50,400 --> 00:09:53,080 It sounds like a Robert Ludlam thriller, The Zeeman Effect. 210 00:09:53,120 --> 00:09:55,520 It does, doesn't it? It sounds very dramatic. 211 00:09:55,520 --> 00:09:57,480 It's fundamental quantum mechanics. 212 00:09:57,520 --> 00:10:00,600 But you know it is thrilling in its own way because this is the 213 00:10:00,600 --> 00:10:03,080 mechanism that makes the whole technique possible. 214 00:10:03,280 --> 00:10:05,680 So what happens? What is the Zeeman Effect? 215 00:10:05,680 --> 00:10:09,840 OK, so imagine you have a beaker of water sitting on your desk. 216 00:10:10,320 --> 00:10:13,440 Inside that water you have billions upon billions of 217 00:10:13,440 --> 00:10:15,240 hydrogen nuclei. All with spin. 218 00:10:15,400 --> 00:10:18,160 All with spin. But under normal conditions 219 00:10:18,160 --> 00:10:21,360 they're all pointing in completely random directions. 220 00:10:21,760 --> 00:10:25,880 Up, down, left, right, diagonal. It's total chaos. 221 00:10:25,880 --> 00:10:27,440 Because they're just tumbling around in the liquid. 222 00:10:27,720 --> 00:10:31,000 Right, and because all their tiny magnetic fields are random, 223 00:10:31,000 --> 00:10:34,840 they all cancel each other out. There's no net magnetization in 224 00:10:34,840 --> 00:10:37,480 the sample, it's just a 0 sum. But then you put it in the 225 00:10:37,480 --> 00:10:39,360 magnet. But then you place it inside a 226 00:10:39,360 --> 00:10:43,200 powerful magnetic field, which we call B naughty or B0, and 227 00:10:43,200 --> 00:10:45,360 they're forced to organize the notes. 228 00:10:45,360 --> 00:10:48,000 Use the analogy of compass needles. 229 00:10:48,160 --> 00:10:50,040 Right. A compass needle always wants to 230 00:10:50,040 --> 00:10:52,480 align with the Earth's magnetic field. 231 00:10:52,600 --> 00:10:54,320 It points north. Correct. 232 00:10:54,440 --> 00:10:58,320 So the think of these nuclei as tiny, tiny bar magnets. 233 00:10:58,440 --> 00:11:00,480 When you turn on the big external magnet, they want to 234 00:11:00,480 --> 00:11:02,840 align with it. However, quantum mechanics is 235 00:11:02,840 --> 00:11:05,600 weird, always. Unlike a compass needle that can 236 00:11:05,600 --> 00:11:08,640 point, you know, slightly northeast if you wiggle it. 237 00:11:08,960 --> 00:11:12,080 A spin 12 nucleus only has two allowed choices. 238 00:11:12,080 --> 00:11:14,400 It's quantized. Two discrete states, no in 239 00:11:14,400 --> 00:11:15,720 between. No in between. 240 00:11:15,720 --> 00:11:18,440 It can align with the field, we call that the alpha state or the 241 00:11:18,440 --> 00:11:21,200 low energy state. Or it can align against the 242 00:11:21,200 --> 00:11:23,400 field, the beta state, the high energy state. 243 00:11:23,400 --> 00:11:25,480 So it's either standing on its feet, meter standing on its 244 00:11:25,480 --> 00:11:27,640 head, that's it. That is it. 245 00:11:28,200 --> 00:11:31,280 And the splitting of the energy levels, the creation of a low 246 00:11:31,280 --> 00:11:33,360 energy level and a high energy level where there was none 247 00:11:33,360 --> 00:11:35,600 before. That is the Zeeman effect. 248 00:11:35,600 --> 00:11:38,000 Now here's the part in the math that I found fascinating. 249 00:11:39,640 --> 00:11:42,880 You would think intuitively that everything would just want to be 250 00:11:42,880 --> 00:11:45,240 in the low energy state, right? You'd think so. 251 00:11:45,360 --> 00:11:47,440 Like a ball rolling down a hill, it's just easier. 252 00:11:47,600 --> 00:11:50,160 Physics usually favors the lowest energy state. 253 00:11:50,160 --> 00:11:54,040 That's a good rule of thumb, but we're at room temperature and 254 00:11:54,040 --> 00:11:58,640 thermal energy, just the ambient heat of the room, is constantly 255 00:11:58,640 --> 00:12:00,720 kicking these atoms around. There's battle going. 256 00:12:00,720 --> 00:12:03,440 On there is it's enough energy to kick a lot of them up into 257 00:12:03,440 --> 00:12:05,360 that high energy standing on their head state. 258 00:12:05,680 --> 00:12:09,040 So you've got this constant battle, the magnet trying to 259 00:12:09,080 --> 00:12:11,720 pull them all down into alignment, and the heat trying 260 00:12:11,720 --> 00:12:16,080 to scramble them all up again. So who wins? 261 00:12:16,520 --> 00:12:19,440 What's the score in that battle? The score is incredibly, 262 00:12:19,440 --> 00:12:22,320 incredibly close. The difference in the population 263 00:12:22,320 --> 00:12:25,840 between the aligned spins and the opposed spins is defined by 264 00:12:25,840 --> 00:12:28,800 something called the Boltzmann distribution, and the difference 265 00:12:28,800 --> 00:12:30,920 is tiny. How tiny are we talking? 266 00:12:31,160 --> 00:12:35,400 We are talking minuscule at room temperature inside a standard 267 00:12:35,400 --> 00:12:40,160 NMR magnet, for every 1,000,000 spins pointing against the field 268 00:12:40,520 --> 00:12:43,200 in the high energy state, a million, you might have 269 00:12:43,200 --> 00:12:46,440 1,000,010 pointing with the field in the low energy. 270 00:12:46,520 --> 00:12:47,840 That's it. A difference of. 10 out of a 271 00:12:47,840 --> 00:12:50,720 million, that is. It that tiny excess, that 272 00:12:50,720 --> 00:12:54,320 handful of extra nuclei that the magnet managed to win over from 273 00:12:54,320 --> 00:12:57,640 the heat, that is the only reason NMR works at all? 274 00:12:57,680 --> 00:13:01,960 Wow, that tiny net magnetization is the only thing we can detect 275 00:13:01,960 --> 00:13:04,480 that blows my. Mind so we are building these 276 00:13:04,480 --> 00:13:08,640 massive multi $1,000,000 machines, cooling them with 277 00:13:08,640 --> 00:13:12,240 liquid helium just to talk to those ten extra guy if the. 278 00:13:12,240 --> 00:13:15,120 Populations were exactly equal 5050. 279 00:13:15,200 --> 00:13:17,560 The signals would cancel out perfectly, we would see 280 00:13:17,560 --> 00:13:20,320 absolutely nothing. We are operating on the absolute 281 00:13:20,320 --> 00:13:23,040 razor's edge of detectability. It really just. 282 00:13:23,040 --> 00:13:25,440 Speaks to the sensitivity of the equipment we're using, which 283 00:13:25,440 --> 00:13:27,280 brings. Us nicely to our next segment, 284 00:13:27,360 --> 00:13:30,520 the machine itself, because you can't just use a fridge magnet 285 00:13:30,520 --> 00:13:32,360 to get that separation. Oh no to. 286 00:13:32,360 --> 00:13:34,360 Get a difference of even 10 per million. 287 00:13:34,360 --> 00:13:36,960 You need a magnetic field that is monstrously strong. 288 00:13:37,200 --> 00:13:39,960 The notes mentioned superconducting magnets, yes. 289 00:13:40,440 --> 00:13:44,200 In the early days of NMR, they used a big electromagnet. 290 00:13:44,200 --> 00:13:48,000 It's basically huge iron cores wrapped in tons of copper wire. 291 00:13:48,480 --> 00:13:50,320 But they were limited. They got really hot. 292 00:13:50,440 --> 00:13:53,320 I can imagine to get the field strengths we use today, which we 293 00:13:53,320 --> 00:13:56,720 need to widen that energy gap and get a better, stronger 294 00:13:56,720 --> 00:14:00,880 signal, we need fields up to say 23 Tesla. 295 00:14:01,120 --> 00:14:03,200 OK, let's. Contextualize 23 Tesla for a 296 00:14:03,200 --> 00:14:05,520 second. A strong fridge magnet is what, 297 00:14:05,520 --> 00:14:07,840 .01 Tesla? Something like that, Something 298 00:14:07,840 --> 00:14:08,560 in that. Ballpark. 299 00:14:08,560 --> 00:14:10,000 Yeah, it's tiny. And an MRI. 300 00:14:10,120 --> 00:14:13,720 Machine at a hospital which is basically just a giant NMR for 301 00:14:13,720 --> 00:14:16,480 people. That's usually 1.5 or maybe 3 302 00:14:16,480 --> 00:14:19,840 Tesla, correct? So 23 Tesla is an immense amount 303 00:14:19,840 --> 00:14:22,320 of energy concentrated in a very small space. 304 00:14:22,320 --> 00:14:24,560 So how do you? Generate a field that's strong 305 00:14:24,560 --> 00:14:26,160 without melting the building down. 306 00:14:26,160 --> 00:14:27,920 You have to. Eliminate electrical resistance. 307 00:14:27,920 --> 00:14:30,640 If you tried to pump that much current through a normal copper 308 00:14:30,640 --> 00:14:34,120 wire, it would just glow white hot and vaporize instantly. 309 00:14:34,200 --> 00:14:37,160 So we use superconducting alloys, usually something like 310 00:14:37,160 --> 00:14:41,520 niobium tin or niobium titanium. When you cool these materials 311 00:14:41,520 --> 00:14:45,480 down to near absolute zero, their electrical resistance 312 00:14:45,480 --> 00:14:50,080 drops to exactly 00. Resistance means zero heat and 313 00:14:50,080 --> 00:14:52,680 the current. Just flows forever unimpeded. 314 00:14:53,120 --> 00:14:56,280 But to keep them that cold, you need a constant supply of liquid 315 00:14:56,280 --> 00:14:58,880 helium, which is why these. Magnets are always housed in 316 00:14:58,880 --> 00:15:00,920 those giant thermos looking canisters. 317 00:15:00,920 --> 00:15:03,320 Exactly. The coil of wire is sitting in a 318 00:15:03,320 --> 00:15:06,720 bath of liquid helium at about four Kelvin 4 Kelvin. 319 00:15:06,720 --> 00:15:11,560 That's -269°C, just 4. Degrees above the coldest 320 00:15:11,560 --> 00:15:13,280 possible temperature in the universe. 321 00:15:13,280 --> 00:15:15,400 It's just an. Extreme environment to enable an 322 00:15:15,400 --> 00:15:16,920 incredibly sensitive measurement. 323 00:15:17,480 --> 00:15:20,120 But the notes also emphasize something else about the magnet 324 00:15:20,600 --> 00:15:22,520 shimming. It says the field must be 325 00:15:22,520 --> 00:15:24,280 extremely homogeneous. This is. 326 00:15:24,360 --> 00:15:26,360 Absolutely. Critical homogeneity just means 327 00:15:26,360 --> 00:15:30,080 sameness. If the magnetic field is 23.0000 328 00:15:30,080 --> 00:15:32,840 Tesla at the top of your sample tube, it better be. 329 00:15:32,840 --> 00:15:37,160 Exactly 23.00000 Tesla at the bottom and in the middle. 330 00:15:37,160 --> 00:15:38,200 And on the left and on the right. 331 00:15:38,200 --> 00:15:41,000 It has to be perfectly uniform across the entire sample. 332 00:15:41,000 --> 00:15:42,920 Why does that matter? So much because the. 333 00:15:42,920 --> 00:15:46,880 Frequency at which a nucleus resonates its musical note, so 334 00:15:46,880 --> 00:15:50,120 to speak, depends directly on the strength of the magnetic 335 00:15:50,120 --> 00:15:54,200 field it's feeling. So if the field is lumpy, little 336 00:15:54,200 --> 00:15:57,440 stronger over here, a little weaker over there, then 337 00:15:57,600 --> 00:16:00,280 identical nuclei in your sample will be singing at slightly 338 00:16:00,280 --> 00:16:01,480 different notes. It's like an. 339 00:16:01,480 --> 00:16:04,560 Orchestra where every musician is slightly out of tune. 340 00:16:04,560 --> 00:16:05,840 That's a perfect. Analogy. 341 00:16:06,080 --> 00:16:09,040 Instead of getting a sharp clear note, which is a sharp peak in 342 00:16:09,040 --> 00:16:14,320 your spectrum, you get a fuzzy, muddy sound, A broad ugly peak 343 00:16:14,320 --> 00:16:16,760 because. Shimming is the process of 344 00:16:16,760 --> 00:16:20,360 tuning the orchestra it. Is we use a series of small 345 00:16:20,360 --> 00:16:23,920 extra coils to tweak and nudge the magnetic field, smoothing 346 00:16:23,920 --> 00:16:26,520 out all the limps until it's as close to perfect as we can get 347 00:16:26,520 --> 00:16:28,800 it, I always thought. Shimming was such a funny word 348 00:16:28,800 --> 00:16:31,400 for high tech physics. It reminds me of sticking a 349 00:16:31,400 --> 00:16:34,800 folded piece of cardboard under a wobbly table leg that. 350 00:16:34,800 --> 00:16:36,440 Is exactly where the term comes from. 351 00:16:36,440 --> 00:16:39,160 It's an old carpentry term. We're just shimming the magnetic 352 00:16:39,160 --> 00:16:41,760 field instead of a table leg to make it perfectly level. 353 00:16:41,920 --> 00:16:44,200 So we have. Our frozen Monster Magnet. 354 00:16:44,360 --> 00:16:46,480 We have our field shimmed to perfection. 355 00:16:47,000 --> 00:16:49,160 Now we need to prepare the suspect, the sample. 356 00:16:49,280 --> 00:16:52,800 The notes here say complete dissolution is essential for 357 00:16:52,800 --> 00:16:53,840 solution. NMR. 358 00:16:53,840 --> 00:16:57,680 Yes, this is the standard method for most small molecules. 359 00:16:58,040 --> 00:17:00,160 You have to dissolve your sample in a solvent. 360 00:17:00,680 --> 00:17:03,600 But you have to be very careful about which solvent you choose, 361 00:17:03,600 --> 00:17:04,319 right? You can't. 362 00:17:04,319 --> 00:17:06,200 Just use tap water. Well, think about. 363 00:17:06,200 --> 00:17:11,400 It water is H2O, It is packed to the gills with protons, billions 364 00:17:11,400 --> 00:17:13,280 and millions of them, and your. Sample. 365 00:17:13,280 --> 00:17:16,200 The drug of the molecule you just made might be very dilute. 366 00:17:16,280 --> 00:17:18,680 Exactly. If you ran that sample in 367 00:17:18,680 --> 00:17:22,359 regular water, the signal from the water's protons would be 368 00:17:22,359 --> 00:17:25,560 like a jet engine roaring, and your sample signal would be a 369 00:17:25,560 --> 00:17:27,119 tiny whisper. You'd never hear it. 370 00:17:27,480 --> 00:17:29,760 So we. Use deuterated solvents right 371 00:17:29,880 --> 00:17:31,760 we? Take a common like chloroform 372 00:17:31,760 --> 00:17:35,280 CHCL 3 and we replace the regular hydrogen, the proton, 373 00:17:35,280 --> 00:17:39,160 with its isotope deuterium, hydrogen 2, hydrogen 2 and 374 00:17:39,160 --> 00:17:41,520 deuterium has completely different resonant frequency 375 00:17:41,520 --> 00:17:43,840 from a proton. It's effectively invisible in 376 00:17:43,840 --> 00:17:45,840 the channel we're listening to, so it's like putting. 377 00:17:45,840 --> 00:17:48,800 An invisibility cloak on the solvent so we can see the salute 378 00:17:48,800 --> 00:17:49,640 clearly. That's. 379 00:17:49,720 --> 00:17:52,880 Precisely what it is OK. Samples in the tube, magnet is 380 00:17:52,880 --> 00:17:56,280 on, nuclei are aligned. We've got our tiny ten in a 381 00:17:56,280 --> 00:17:59,720 million excess pointing up up. Now how do we get the signal? 382 00:17:59,720 --> 00:18:02,360 Do we just, I don't know, put a tiny microphone up to the tube, 383 00:18:02,760 --> 00:18:05,200 not? Anymore, In the old days, what 384 00:18:05,200 --> 00:18:09,040 we call continuous wave or CWMR, it was kind of like that. 385 00:18:09,040 --> 00:18:11,320 We used to slowly sweep the frequency. 386 00:18:11,400 --> 00:18:13,200 How do you mean? It was like turning the dial on 387 00:18:13,200 --> 00:18:15,960 an old analog radio searching for a station. 388 00:18:15,960 --> 00:18:23,600 You'd go 99.1 megahertz static, 99.2 static, 99.3 BEP. 389 00:18:24,080 --> 00:18:28,560 Found one and that must have. Taken forever, it did. 5/10/15 390 00:18:28,560 --> 00:18:30,800 minute for a simple scan. It was incredibly slow and 391 00:18:30,800 --> 00:18:33,440 inefficient, but now we use. The pulse method pulse NMR. 392 00:18:33,440 --> 00:18:37,480 Or more accurately, Fourier transform NMRFTNMR. 393 00:18:37,800 --> 00:18:40,600 Instead of carefully searching for each individual frequency, 394 00:18:40,760 --> 00:18:42,880 we basically hit the sample with a sledgehammer. 395 00:18:42,920 --> 00:18:45,440 A sledgehammer. Made of radio waves, yes. 396 00:18:46,000 --> 00:18:50,000 A short, very powerful pulse of radiofrequency energy. 397 00:18:50,720 --> 00:18:52,760 And because the pulse is so short, we're talking 398 00:18:52,760 --> 00:18:55,280 microseconds long. It contains a widespread of 399 00:18:55,280 --> 00:18:57,240 frequencies. It basically contains all the 400 00:18:57,240 --> 00:18:59,880 frequencies we might be interested in all at once. 401 00:19:00,240 --> 00:19:03,360 The analogy I loved from the reading, and I want to really 402 00:19:03,480 --> 00:19:06,240 dig into this, was the idea of striking a bell. 403 00:19:06,360 --> 00:19:08,040 It is the perfect. Analogy for this. 404 00:19:08,080 --> 00:19:10,200 Imagine you have a large church bell. 405 00:19:10,640 --> 00:19:13,080 If you wanted to figure out what frequency it rings at, you 406 00:19:13,080 --> 00:19:15,880 wouldn't tap it with a tuning fork at 100 Hertz, then listen, 407 00:19:15,880 --> 00:19:17,640 then try 101 Hertz. No, that would. 408 00:19:17,640 --> 00:19:19,400 Take all day. You'd go crazy, right? 409 00:19:19,400 --> 00:19:20,880 You just take. A big hammer and you hit it. 410 00:19:21,000 --> 00:19:23,920 WHECK and the Bell. Rings it. 411 00:19:23,920 --> 00:19:26,920 Rings at all of its natural resonant frequencies 412 00:19:26,920 --> 00:19:30,760 simultaneously. It produces a complex rich tone 413 00:19:30,760 --> 00:19:33,040 that fades overtime. We do the exact same thing to 414 00:19:33,040 --> 00:19:35,280 the molecule. We hit it with the RF pulse, and 415 00:19:35,280 --> 00:19:37,400 that excites all the different nuclei at the same time. 416 00:19:37,440 --> 00:19:39,880 So physically. What is happening to those spins 417 00:19:39,880 --> 00:19:41,680 when the pulse hits them? The pulse. 418 00:19:41,680 --> 00:19:44,960 Imparts energy and it rotates that net magnetization we talked 419 00:19:44,960 --> 00:19:47,960 about. It tips it over a standard 90° 420 00:19:47,960 --> 00:19:52,240 pulse, pushes it 90° from the Z axis where it's aligned with the 421 00:19:52,240 --> 00:19:54,240 magnet, so from standing. Up into. 422 00:19:54,320 --> 00:19:56,560 The transverse plane, the XY plane 2 lying. 423 00:19:56,560 --> 00:19:58,120 Flat on its back? Exactly. 424 00:19:58,280 --> 00:20:01,200 And once those spins are in that transverse plane, the main 425 00:20:01,200 --> 00:20:04,560 magnet B naughty grabs hold of them and they start to precess. 426 00:20:04,560 --> 00:20:07,480 They start to spin around the Z axis like a spinning. 427 00:20:07,480 --> 00:20:10,560 Top that's been tipped over and it starts wobbling in a circle 428 00:20:10,560 --> 00:20:11,760 before it falls. That's the. 429 00:20:11,760 --> 00:20:16,800 Exact motion, and as this net magnetic moment spins around, it 430 00:20:16,800 --> 00:20:20,720 passes by a receiver coil which is just a fancy loop of wire 431 00:20:20,720 --> 00:20:24,240 inside the machine and a. Moving magnet next to a wire 432 00:20:24,680 --> 00:20:26,560 that induces a current it induces. 433 00:20:26,560 --> 00:20:29,160 A tiny voltage, and that voltage is our signal. 434 00:20:29,160 --> 00:20:31,960 That is the. FID, the free induction decay 435 00:20:31,960 --> 00:20:33,520 The FI. D Free induction. 436 00:20:33,520 --> 00:20:35,240 Decay. It really sounds like an indie 437 00:20:35,240 --> 00:20:37,560 rock band from the early 2000s. It would be a. 438 00:20:37,560 --> 00:20:41,960 Great band name, I agree, but physically it's the raw signal 439 00:20:41,960 --> 00:20:44,960 coming out of the machine. It's free because it happens 440 00:20:44,960 --> 00:20:48,000 after the pulse is off, Induction because it's an 441 00:20:48,000 --> 00:20:52,200 induced voltage, and decay because as the spins relax and 442 00:20:52,200 --> 00:20:55,240 go back to equilibrium, the signal fades out to nothing. 443 00:20:55,840 --> 00:20:58,000 Now the. Notes show a picture of an fid 444 00:20:58,480 --> 00:21:01,520 and it doesn't look like a nice neat graph with peaks. 445 00:21:01,880 --> 00:21:04,760 It looks like a squiggle. It looks like the audio file of 446 00:21:04,760 --> 00:21:07,960 a complex chord being played on a piano and then fading out, 447 00:21:08,520 --> 00:21:09,800 that is. Exactly what it is. 448 00:21:09,840 --> 00:21:13,160 It's a complex chord. It's every nucleus in your 449 00:21:13,160 --> 00:21:16,880 molecule singing its own unique note, all at the same time, all 450 00:21:16,880 --> 00:21:18,200 added together. It's what we call a. 451 00:21:18,200 --> 00:21:21,480 Time domain signal, yes. It's amplitude versus time. 452 00:21:21,480 --> 00:21:23,400 And you're right, you can't just look at that squiggle and say, 453 00:21:23,680 --> 00:21:25,440 oh, look, there's a methyl group over there. 454 00:21:25,520 --> 00:21:27,600 It's impossible. For a human to read completely, 455 00:21:27,600 --> 00:21:28,920 we need. To decode it, we need to 456 00:21:28,920 --> 00:21:32,160 mathematically separate that complex chord back into its 457 00:21:32,200 --> 00:21:34,080 individual notes. And that's where the magic comes 458 00:21:34,080 --> 00:21:36,400 in. The Fourier transform, the FT, 459 00:21:36,520 --> 00:21:38,440 the mathematical. Magic trick it really. 460 00:21:38,520 --> 00:21:42,280 Really feels like magic. The Fourier transform is a 461 00:21:42,280 --> 00:21:46,040 powerful algorithm that converts a signal from the time domain, 462 00:21:46,440 --> 00:21:49,920 our squiggle, into the frequency domain, which is intensity 463 00:21:49,920 --> 00:21:51,560 versus frequency. It takes the. 464 00:21:51,560 --> 00:21:54,160 Recording of the Symphony and turns it back into the sheet 465 00:21:54,160 --> 00:21:57,160 music that is a. Beautiful way to put it, yes, it 466 00:21:57,160 --> 00:22:00,720 breaks the complex wave down into the individual sine waves 467 00:22:00,720 --> 00:22:03,440 that built it up. And because we pulsed everything 468 00:22:03,440 --> 00:22:06,680 at once and did this conversion, we get the entire spectrum in 469 00:22:06,680 --> 00:22:09,760 about 5 seconds 5. Seconds instead of 5 minutes a 470 00:22:09,760 --> 00:22:12,000 huge. Leap forward, so the output. 471 00:22:12,000 --> 00:22:14,960 Of this transformation is the spectrum we all know and love 472 00:22:15,000 --> 00:22:18,800 from chemistry textbooks, the graph with all the peaks on the 473 00:22:18,800 --> 00:22:20,880 page. Now we get to the real detective 474 00:22:20,880 --> 00:22:22,000 work. Now we decode. 475 00:22:22,000 --> 00:22:23,760 The message we have? These peaks. 476 00:22:23,760 --> 00:22:26,240 Some are tall, some are short, some are single lines, some are 477 00:22:26,240 --> 00:22:28,680 split into patterns. What are they telling us about 478 00:22:28,680 --> 00:22:30,360 the molecule in? Solution. 479 00:22:30,360 --> 00:22:32,280 NMR. They tell us a number of things, 480 00:22:32,440 --> 00:22:34,400 but let's focus on the big two for now. 481 00:22:34,720 --> 00:22:37,000 Chemical shift and coupling. Let's start with. 482 00:22:37,000 --> 00:22:40,160 Chemical shift, Yeah, This is the location of the peak on the 483 00:22:40,160 --> 00:22:42,040 horizontal axis, right? Correct. 484 00:22:42,160 --> 00:22:46,720 We measure it in a unit called PPM or parts per million, and 485 00:22:46,720 --> 00:22:50,200 the location the chemical shift tells you about the electronic 486 00:22:50,200 --> 00:22:52,720 environment of that particular nucleus. 487 00:22:52,880 --> 00:22:54,240 Electronic. Environment. 488 00:22:54,360 --> 00:22:57,120 That sounds a little vague. What does that mean in practical 489 00:22:57,120 --> 00:22:58,320 terms? It basically. 490 00:22:58,320 --> 00:23:00,720 Means who are your neighbors and what are they doing? 491 00:23:01,240 --> 00:23:04,080 Remember, a nucleus is surrounded by a cloud of 492 00:23:04,080 --> 00:23:06,960 electrons, right? And those electrons are also 493 00:23:06,960 --> 00:23:11,200 charged particles and they're moving in loops in orbitals. 494 00:23:11,200 --> 00:23:14,400 They create their own Piney little magnetic fields. 495 00:23:14,400 --> 00:23:16,440 So they're like. Little magnets too, and these 496 00:23:16,440 --> 00:23:18,640 tiny. Fields usually oppose the big 497 00:23:18,640 --> 00:23:22,080 magnet that we've applied. They effectively shield the 498 00:23:22,080 --> 00:23:24,960 nucleus from the full force of the external field. 499 00:23:25,040 --> 00:23:27,200 So the nucleus. Is kind of hiding behind a wall 500 00:23:27,200 --> 00:23:30,240 of its own electrons, yes. And if a nucleus is well 501 00:23:30,240 --> 00:23:33,280 shielded, it feels a slightly weaker magnetic field. 502 00:23:33,280 --> 00:23:36,080 It spins a little slower. It shows up on the right hand 503 00:23:36,080 --> 00:23:38,320 side of the graph at a low PPM value. 504 00:23:38,320 --> 00:23:40,080 We call that upfield. But what if you? 505 00:23:40,080 --> 00:23:43,880 Attach that carbon or that proton to something greedy like 506 00:23:43,880 --> 00:23:45,920 an oxygen atom or a chlorine atom. 507 00:23:46,120 --> 00:23:48,200 Electronegativity. Exactly. 508 00:23:48,320 --> 00:23:50,760 An atom, like oxygen is an electron hog. 509 00:23:51,040 --> 00:23:54,480 It pulls that electron blanket away from the carbon, so the 510 00:23:54,480 --> 00:23:56,120 carbon. Is left out in the cold. 511 00:23:56,320 --> 00:23:57,640 It's exposed. It is. 512 00:23:57,680 --> 00:24:02,000 Deshielded it feels more of the full force of the big magnet, so 513 00:24:02,000 --> 00:24:04,160 it spins faster. It resonates at a higher 514 00:24:04,160 --> 00:24:08,040 frequency and its peak shifts to the left on the graph to a 515 00:24:08,040 --> 00:24:10,880 higher PPM value. We call that downfield. 516 00:24:10,920 --> 00:24:12,320 So chemical. Shift is basically a 517 00:24:12,320 --> 00:24:15,800 neighborhood check. If your peak is at 10 PPM, 518 00:24:15,920 --> 00:24:19,160 you're living in a nice quiet suburb surrounded by other 519 00:24:19,160 --> 00:24:22,600 carbons and hydrogens. If you're 2 PPM, you're living 520 00:24:22,600 --> 00:24:25,280 right next to a factory. Like an oxygen double bond. 521 00:24:25,480 --> 00:24:26,760 That's a great. Way to think about it. 522 00:24:26,760 --> 00:24:28,800 It tells you what kind of functional group you're looking 523 00:24:28,800 --> 00:24:31,280 at. But then then there's coupling. 524 00:24:31,280 --> 00:24:33,160 This is where it gets really, really detailed. 525 00:24:33,160 --> 00:24:35,200 This is the neighbor. Effect you mentioned earlier, we 526 00:24:35,200 --> 00:24:36,720 call it. Spin, Spin coupling. 527 00:24:37,000 --> 00:24:40,120 What it means is that a nucleus isn't just feeling the big 528 00:24:40,120 --> 00:24:43,880 external magnet, it's also feeling the tiny magnetic fields 529 00:24:43,880 --> 00:24:46,760 of the specific nuclei that are right next door to it through 530 00:24:46,760 --> 00:24:48,280 the chemical bonds they're whispering. 531 00:24:48,280 --> 00:24:50,360 To each other through the bonds they are. 532 00:24:50,480 --> 00:24:53,840 And this can be communication creates splitting a single peak, 533 00:24:53,840 --> 00:24:57,520 instead of being a sharp line splits into two or three or four 534 00:24:57,520 --> 00:24:59,920 smaller picks and multiplets. These are the multiplets. 535 00:24:59,920 --> 00:25:02,360 And the pattern tells you exactly how many neighbors you 536 00:25:02,360 --> 00:25:06,160 have on adjacent atoms. If you have one neighbor, that 537 00:25:06,160 --> 00:25:09,920 neighbor's spin can be either up or down relative to the big 538 00:25:09,920 --> 00:25:11,800 magnet, so there are two. Possibilities. 539 00:25:11,920 --> 00:25:14,400 Two possibilities. So your signal gets split into 540 00:25:14,400 --> 00:25:18,720 two distinct peaks of equal height at double it, and if you 541 00:25:18,720 --> 00:25:20,480 have two. Equivalent neighbors while 542 00:25:20,480 --> 00:25:22,400 their. Spins can be up, up or down, 543 00:25:22,400 --> 00:25:25,560 down or 1 can be up and 1 can be down and there are two ways to 544 00:25:25,560 --> 00:25:28,120 get that up, down or down, up. So that's. 545 00:25:28,120 --> 00:25:30,560 Three possible empty states, right? 546 00:25:30,760 --> 00:25:34,840 Which means your signal splits into three peaks, a triplet with 547 00:25:34,840 --> 00:25:37,000 a one to two to one ratio of heights. 548 00:25:37,000 --> 00:25:39,720 This is the famous. N + 1 rule they teach in organic 549 00:25:39,720 --> 00:25:42,360 chemistry it is. But the lecture notes we have 550 00:25:42,360 --> 00:25:44,280 here go deeper than just counting neighbors. 551 00:25:44,280 --> 00:25:47,000 They talk about the coupling constant, which is denoted by 552 00:25:47,000 --> 00:25:48,600 the letter J. This is the. 553 00:25:48,600 --> 00:25:50,920 Physical distance between the tips of those split peaks, 554 00:25:50,920 --> 00:25:53,560 right, Right. And it's measured in Hertz, yes. 555 00:25:53,960 --> 00:25:57,560 Not in PPM, but in Hertz. Yeah, and the coupling constant 556 00:25:57,560 --> 00:26:01,160 is an absolute treasure trove of structural information. 557 00:26:01,760 --> 00:26:04,400 It tells us about the nature of the bond connecting the two 558 00:26:04,400 --> 00:26:05,560 atoms. How so? 559 00:26:05,720 --> 00:26:08,360 For example, the lecture notes highlight the one bond carbon 560 00:26:08,360 --> 00:26:12,160 hydrogen coupling, which they write as $1.00 JCH 1 bond. 561 00:26:12,160 --> 00:26:15,200 Coupling OK and the notes point. Out that this value changes in a 562 00:26:15,200 --> 00:26:18,120 very predictable way based on the hybridization of the carbon 563 00:26:18,120 --> 00:26:20,840 atom hybridization. So whether it has single, double 564 00:26:20,840 --> 00:26:23,800 or triple bonds, exactly. It's just a fancy way of saying 565 00:26:23,800 --> 00:26:27,960 how the electrons are arranged in the bonds and CP33 carbon 566 00:26:27,960 --> 00:26:31,640 like in ethane, all single bonds tetrahedral shape has a coupling 567 00:26:31,640 --> 00:26:35,960 constant of about 125 Hertz. OK, one. 25 I'll remember that 568 00:26:35,960 --> 00:26:39,800 now an SP2. 2 carbon like in ethane with a double bond flat 569 00:26:39,800 --> 00:26:43,560 shape that value jumps up to around 160 Hertz a noticeable. 570 00:26:43,560 --> 00:26:46,240 Increase, but then you get. To an SP carbon like in 571 00:26:46,240 --> 00:26:50,080 Acetylene with the triple bond linear shape and the coupling 572 00:26:50,080 --> 00:26:52,080 constant is huge. It's 250 Hertz. 573 00:26:52,080 --> 00:26:54,640 Wow, that's double. The first one, 125 versus 250, 574 00:26:54,880 --> 00:26:57,360 it's a massive. Difference, and it has to do 575 00:26:57,360 --> 00:27:01,120 with this character of the bond. This orbital is spherical and 576 00:27:01,120 --> 00:27:03,120 it's held very close to the nucleus. 577 00:27:03,200 --> 00:27:05,440 OK. The more character a bond has, 578 00:27:05,760 --> 00:27:09,040 the closer the bonding electrons are to the nucleus and the 579 00:27:09,040 --> 00:27:11,800 stronger the magnetic communication is between the 580 00:27:11,800 --> 00:27:13,640 carbon and the hydrogen. So just by. 581 00:27:13,640 --> 00:27:16,480 Taking a ruler to your spectrum and measuring the distance 582 00:27:16,480 --> 00:27:20,200 between the peaks, you know if you have a single, double or 583 00:27:20,200 --> 00:27:22,960 triple bond, without a doubt. It's an incredibly powerful 584 00:27:22,960 --> 00:27:25,880 diagnostic tool, but the. Section in the sources that 585 00:27:25,880 --> 00:27:28,480 really made me feel like Sherlock Holmes was the 586 00:27:28,480 --> 00:27:32,120 inorganic chemistry part, specifically the bit about the 587 00:27:32,120 --> 00:27:33,800 platinum complexes. Oh, this is a. 588 00:27:33,800 --> 00:27:37,320 Classic application of coupling constants distinguishing between 589 00:27:37,320 --> 00:27:39,800 isomers and isomers. Are just molecules that have the 590 00:27:39,800 --> 00:27:42,760 same atoms, but they're arranged differently in space, right? 591 00:27:42,760 --> 00:27:44,000 So. Let's take the example from the 592 00:27:44,000 --> 00:27:45,560 notes. You have a platinum atom in the 593 00:27:45,560 --> 00:27:49,080 center and attached to it are two chlorine atoms and two 594 00:27:49,080 --> 00:27:52,440 phosphorus containing ligands. These PT three groups and. 595 00:27:52,440 --> 00:27:55,240 You can arrange those four pieces in two main ways. 596 00:27:55,760 --> 00:27:58,960 You can put the two phosphoruses next to each other at a 90° 597 00:27:58,960 --> 00:28:01,480 angle, that's the CIS isomer. Or you can. 598 00:28:01,480 --> 00:28:04,760 Put them on opposite sides of the platinum at 180°. 599 00:28:04,960 --> 00:28:06,760 That's the trans isomer, and to the naked. 600 00:28:06,760 --> 00:28:08,440 Eye. If you had a bottle of each, 601 00:28:08,640 --> 00:28:10,520 they'd both probably just be white powders. 602 00:28:10,520 --> 00:28:12,160 You couldn't tell them apart. Not a chance. 603 00:28:12,560 --> 00:28:16,520 But in an NMR spectrum, they scream their identities at you 604 00:28:16,640 --> 00:28:18,400 and the key. Is the coupling between the 605 00:28:18,400 --> 00:28:20,480 platinum and the phosphorus atoms right? 606 00:28:20,680 --> 00:28:22,800 Well, even. More telling is the coupling 607 00:28:22,800 --> 00:28:26,400 between the two phosphorus atoms themselves through the platinum, 608 00:28:26,480 --> 00:28:28,840 and the rule is simple and powerful. 609 00:28:29,080 --> 00:28:33,240 Transnuclei couple much much more strongly than CIS nuclei. 610 00:28:33,320 --> 00:28:36,120 Why is? That why does being on opposite 611 00:28:36,120 --> 00:28:39,320 sides make that magnetic connection so much stronger It 612 00:28:39,320 --> 00:28:41,240 comes. Down to the orbitals of the 613 00:28:41,240 --> 00:28:44,080 central metal atom. Again, in the trans arrangement, 614 00:28:44,080 --> 00:28:46,760 the two phosphorus ligands are on opposite sides of the 615 00:28:46,760 --> 00:28:49,080 platinum. They're both interacting with 616 00:28:49,080 --> 00:28:52,000 and communicating through the same dorbitals on the metal. 617 00:28:52,080 --> 00:28:54,120 They have a. Direct Line of sight through the 618 00:28:54,120 --> 00:28:57,160 platinum Adam, that's a great. Way to put it, they're sharing 619 00:28:57,160 --> 00:28:59,960 the same phase of the orbital lobes. 620 00:29:00,080 --> 00:29:03,080 This makes the communication channel incredibly efficient. 621 00:29:03,480 --> 00:29:06,440 The signal is strong. And in the CIS arrangement in 622 00:29:06,440 --> 00:29:08,400 CIS. They're at 90° to each other. 623 00:29:08,560 --> 00:29:10,640 They're interacting with different orbital lobes on the 624 00:29:10,640 --> 00:29:13,000 platinum, and these lobes often have different quantum 625 00:29:13,000 --> 00:29:14,960 mechanical phases. So the communication. 626 00:29:14,960 --> 00:29:16,240 Is poor. It's like trying. 627 00:29:16,240 --> 00:29:19,240 To have a conversation around a corner versus talking to someone 628 00:29:19,240 --> 00:29:21,920 face to face, it's much less efficient. 629 00:29:21,920 --> 00:29:24,120 The source. Notes say that the phosphorus 630 00:29:24,520 --> 00:29:28,040 phosphorus coupling in the CIS compound is an order of 631 00:29:28,040 --> 00:29:30,840 magnitude smaller than in the trans compound. 632 00:29:30,920 --> 00:29:32,920 An order. Of magnitude, that's a factor of 633 00:29:32,920 --> 00:29:34,760 10. It's the difference between a 634 00:29:34,760 --> 00:29:37,400 shout and a whisper. So you run the spectrum, you 635 00:29:37,400 --> 00:29:40,760 measure the J value and boom, you know the exact 3D geometry 636 00:29:40,760 --> 00:29:43,200 of the molecule. No ambiguity, no guessing 637 00:29:43,200 --> 00:29:44,240 required. OK, so this. 638 00:29:44,240 --> 00:29:48,680 Is all incredibly powerful, but up until now we've been living 639 00:29:48,680 --> 00:29:52,280 in a very happy, clean world. We were talking about solution 640 00:29:52,280 --> 00:29:55,280 NMR. The sample is dissolved, the 641 00:29:55,280 --> 00:29:58,160 molecules are tumbling around happily in the solvent, which is 642 00:29:58,160 --> 00:30:00,000 fantastic. When you can actually dissolve 643 00:30:00,000 --> 00:30:03,640 your sample but. Life isn't always a liquid. 644 00:30:03,880 --> 00:30:05,360 No, it's. Not sometimes. 645 00:30:05,360 --> 00:30:07,720 You can't dissolve your sample. Maybe it's a piece of polymer 646 00:30:07,720 --> 00:30:11,240 plastic, maybe it's a bone fragment from an archaeological 647 00:30:11,240 --> 00:30:14,200 dig, or a ceramic. Catalyst, or a protein that's 648 00:30:14,200 --> 00:30:17,200 embedded in a cell membrane. If you dissolve it, you destroy 649 00:30:17,200 --> 00:30:18,640 the very thing you're trying to study. 650 00:30:18,640 --> 00:30:20,360 Exactly. So you have no choice. 651 00:30:20,360 --> 00:30:22,040 You have to analyze it as a solid. 652 00:30:22,800 --> 00:30:27,240 This brings us to segment 4, solid-state and Mr. And from 653 00:30:27,240 --> 00:30:30,080 reading the materials, this sounds like playing the game on 654 00:30:30,080 --> 00:30:31,400 hard mode. It sounds like. 655 00:30:31,400 --> 00:30:34,680 Nightmare mode it is. Absolutely hard mode, because as 656 00:30:34,680 --> 00:30:37,760 the notes make very clear, the moment you stop the molecules 657 00:30:37,760 --> 00:30:40,400 from moving, the physics gets very, very ugly. 658 00:30:40,480 --> 00:30:42,600 Why? Why does stopping the movement 659 00:30:42,720 --> 00:30:45,240 ruin the nice sharp signals we just talked about? 660 00:30:45,440 --> 00:30:47,560 Think back. To the liquid, we said the 661 00:30:47,560 --> 00:30:50,080 molecules in a liquid are tumbling wildly. 662 00:30:50,160 --> 00:30:52,440 Brownian motion. They're spinning and flipping 663 00:30:52,440 --> 00:30:54,160 millions and millions of times every second. 664 00:30:54,320 --> 00:30:56,760 Complete chaos. It's a controlled chaos. 665 00:30:56,960 --> 00:31:00,560 And that rapid tumbling is absolutely crucial because it 666 00:31:00,560 --> 00:31:02,960 averages out all of the interactions that depend on 667 00:31:02,960 --> 00:31:04,920 direction. It's like looking at a fan 668 00:31:04,920 --> 00:31:06,920 that's spinning at high speed. What do you see? 669 00:31:07,080 --> 00:31:09,040 You don't see the. Individual blades you just see a 670 00:31:09,040 --> 00:31:11,480 transparent blur. A disc Exactly. 671 00:31:11,480 --> 00:31:14,400 You see the average of the blade being in every position. 672 00:31:14,720 --> 00:31:17,360 The tumbling does the same thing for the molecule. 673 00:31:17,880 --> 00:31:21,160 It averages out all the messy magnetic interactions to zero, 674 00:31:21,400 --> 00:31:25,000 and that leaves you with those beautiful sharp, clean peaks, 675 00:31:25,000 --> 00:31:26,240 but in a solid. The fan. 676 00:31:26,240 --> 00:31:28,400 Stops. Now you see the blades, the 677 00:31:28,400 --> 00:31:31,440 molecules are locked in place, and because you have a powder 678 00:31:31,440 --> 00:31:35,320 with millions of tiny crystals, the molecules are locked in 679 00:31:35,360 --> 00:31:38,880 every possible orientation relative to the magnetic field. 680 00:31:38,920 --> 00:31:41,480 And the result. Is not a sharp peak the result? 681 00:31:41,480 --> 00:31:45,040 Is a broad, ugly, featureless BLOB. 682 00:31:45,080 --> 00:31:46,440 The broadening. Nightmare. 683 00:31:46,840 --> 00:31:49,000 The notes act like this is a crime scene. 684 00:31:49,240 --> 00:31:53,080 They list 3 specific villains that are responsible for this 685 00:31:53,080 --> 00:31:55,480 broadening the three. Villains of solid-state 686 00:31:55,480 --> 00:31:57,120 broadening. It sounds very dramatic. 687 00:31:57,120 --> 00:31:57,680 It does. Let's. 688 00:31:57,680 --> 00:32:02,400 Name and shame them. Villain #1 CSA Chemical shift 689 00:32:02,400 --> 00:32:04,480 Anisotropy. Anisotropy. 690 00:32:04,480 --> 00:32:07,120 Is a fancy word that just means directionally dependent. 691 00:32:07,120 --> 00:32:10,200 OK, the electron cloud that Shields a nucleus isn't usually 692 00:32:10,200 --> 00:32:12,560 a perfect sphere. It's often shaped more like a 693 00:32:12,560 --> 00:32:14,600 cigar or a pancake or a dumbbell. 694 00:32:14,760 --> 00:32:16,560 So the amount. Of shielding depends on which 695 00:32:16,560 --> 00:32:20,080 way the molecule is facing, yes. If the molecule is standing up 696 00:32:20,080 --> 00:32:23,120 vertically relative to the magnet, the electrons shielded 697 00:32:23,120 --> 00:32:25,440 one way, giving you one chemical shift. 698 00:32:25,680 --> 00:32:28,640 If it's lying down horizontally, they shielded a different way, 699 00:32:28,760 --> 00:32:30,600 giving you a totally different chemical shift. 700 00:32:30,880 --> 00:32:32,840 So 1. Orientation might give you a 701 00:32:32,840 --> 00:32:36,680 peak at 100 PPM, and another orientation of the exact same 702 00:32:36,680 --> 00:32:39,880 molecule gives a peak at 150 PPM precisely. 703 00:32:40,160 --> 00:32:42,840 And in a powder sample, which is just a scoop of powder in a 704 00:32:42,840 --> 00:32:47,240 tube, you have millions of tiny crystals facing every possible 705 00:32:47,240 --> 00:32:48,720 direction at once. So you get. 706 00:32:48,760 --> 00:32:52,000 Every possible chemical shift all at the same time instead of 707 00:32:52,000 --> 00:32:52,760 a. Sharp line. 708 00:32:52,760 --> 00:32:55,520 At the average position, you get a massive smear. 709 00:32:55,600 --> 00:32:58,440 We call it a powder pattern that spans the whole range of 710 00:32:58,440 --> 00:33:00,360 possibilities. It just covers up everything 711 00:33:00,360 --> 00:33:01,440 else a huge. Mess. 712 00:33:01,800 --> 00:33:04,600 OK, villain #2 The Polar. Interaction. 713 00:33:05,000 --> 00:33:09,160 This is the direct through space magnetic pull between nuclei. 714 00:33:09,640 --> 00:33:12,040 Think of 2 little bar magnets sitting on a table. 715 00:33:12,320 --> 00:33:14,800 If they're close to each other, they push and pull on each 716 00:33:14,800 --> 00:33:18,360 other's magnetic fields and in. Liquid this averages out because 717 00:33:18,360 --> 00:33:22,160 they're moving so fast averages. To 0, but in a solid they're 718 00:33:22,160 --> 00:33:25,640 stuck right next to each other. A proton sitting next to a 719 00:33:25,640 --> 00:33:28,480 carbon 13 acts like a local magnetic bully. 720 00:33:28,960 --> 00:33:32,080 It strongly modifies the magnetic field that the carbon 721 00:33:32,080 --> 00:33:33,720 is feeling and this effect. Is big. 722 00:33:34,120 --> 00:33:35,160 It's. Enormous. 723 00:33:35,440 --> 00:33:38,960 The notes say that for a typical proton carbon interaction, it 724 00:33:38,960 --> 00:33:43,720 can be greater than 50 kHz. That's an enormous frequency 725 00:33:43,720 --> 00:33:46,720 range that basically just wipes out any hope of seeing fine 726 00:33:46,720 --> 00:33:47,960 details. It's just noise. 727 00:33:47,960 --> 00:33:51,000 At that point and the third villain, quadrupolar. 728 00:33:51,000 --> 00:33:53,200 Interaction. This one only applies to those 729 00:33:53,200 --> 00:33:54,880 nuclei with a spin greater than 12. 730 00:33:54,880 --> 00:33:57,440 Remember we said spin 12 nuclei are nice and spherical. 731 00:33:57,800 --> 00:34:01,600 Well, nuclei with spin 1 or 32 and so on are non spherical. 732 00:34:01,600 --> 00:34:04,160 They're shaped like a football. They have an electric quadrupole 733 00:34:04,160 --> 00:34:06,320 moment and that interacts. With the crystal it interacts. 734 00:34:06,320 --> 00:34:08,360 With the electric field gradients within the crystal 735 00:34:08,360 --> 00:34:11,040 lattice, and this interaction is usually the strongest of them 736 00:34:11,040 --> 00:34:13,560 all. It can be hundreds of kHz wide, 737 00:34:13,760 --> 00:34:16,840 so we have. CSA Day, polar coupling and 738 00:34:16,840 --> 00:34:20,960 quadrupolar interactions all conspiring to turn our beautiful 739 00:34:20,960 --> 00:34:25,040 informative spectrum into a useless broad mound of noise. 740 00:34:25,880 --> 00:34:28,400 It really does seem hopeless. Why do we even bother with 741 00:34:28,639 --> 00:34:30,520 solid-state NMR? It would be. 742 00:34:30,520 --> 00:34:33,920 Hopeless, if it weren't for some truly incredible engineering and 743 00:34:33,920 --> 00:34:36,080 physics tricks. We can't let the molecules 744 00:34:36,080 --> 00:34:37,760 tumble, so we have to find another way. 745 00:34:37,760 --> 00:34:41,159 We have to artificially make the solid behave like a liquid and 746 00:34:41,159 --> 00:34:42,960 this leads. Us to what is without a doubt 747 00:34:42,960 --> 00:34:45,760 the coolest term in the entire stack of materials. 748 00:34:46,199 --> 00:34:50,000 Magic angle spinning MAS. It sounds like sorcery, doesn't 749 00:34:50,000 --> 00:34:52,960 it? But it's pure beautiful geometry 750 00:34:52,960 --> 00:34:54,440 and mathematics. Explain. 751 00:34:54,440 --> 00:34:56,280 The magic part. Why is it magic? 752 00:34:56,280 --> 00:34:57,840 What's the trick? The trick comes. 753 00:34:57,840 --> 00:35:00,280 From looking at the math that describes those interactions, we 754 00:35:00,280 --> 00:35:03,040 just complained about the CSA and the dipolar coupling. 755 00:35:03,480 --> 00:35:05,920 When you write out the Hamiltonian equations, the 756 00:35:05,920 --> 00:35:09,000 physics formulas for how they brought in the signal, they all 757 00:35:09,000 --> 00:35:12,760 share a common angular term. The exact same piece of math 758 00:35:12,760 --> 00:35:14,160 shows up in all of them. The same. 759 00:35:14,160 --> 00:35:17,280 Geometric factor is responsible for all the trouble in large. 760 00:35:17,280 --> 00:35:20,000 Part Yes and that term is 3 Cos 2. 761 00:35:20,160 --> 00:35:21,360 OK, 3. Cos 2. 762 00:35:21,360 --> 00:35:23,440 I'm visualizing the equation in that. 763 00:35:23,440 --> 00:35:26,360 Equation Theta is the angle between the axis of the 764 00:35:26,360 --> 00:35:29,000 interaction in the molecule and the main magnetic field B 765 00:35:29,000 --> 00:35:31,840 Naughty. Now back in the 1950s a few 766 00:35:31,840 --> 00:35:34,960 clever physicists, Andrew and EADS are the names that come up. 767 00:35:35,240 --> 00:35:38,360 They looked at that equation and had a brilliant idea which was 768 00:35:38,400 --> 00:35:42,040 they said wait a minute, what if I can make that whole term 3 Cos 769 00:35:42,040 --> 00:35:45,960 2/1 equal to 0? If I can do that, the entire 770 00:35:45,960 --> 00:35:49,000 interaction term just vanishes from the equation if that term 771 00:35:49,000 --> 00:35:49,400 is. Zero. 772 00:35:49,400 --> 00:35:51,000 Then the broadening effect goes to 0. 773 00:35:51,320 --> 00:35:52,960 Gone so. You just do the algebra. 774 00:35:52,960 --> 00:35:55,440 You set three Cos of 1, then Cos 2 = 13. 775 00:35:55,640 --> 00:35:57,960 You take the square root, then the inverse cosine and the 776 00:35:57,960 --> 00:35:59,880 answer is drum roll please. Approximately. 777 00:36:00,000 --> 00:36:04,080 A 54.74° The magic angle The magic angle. 778 00:36:04,360 --> 00:36:06,400 It's a fundamental geometric constant. 779 00:36:06,480 --> 00:36:08,800 It's the angle of the diagonal that runs through a cube 780 00:36:08,800 --> 00:36:10,880 connecting opposite corners. So what do we? 781 00:36:10,880 --> 00:36:14,320 Do with this angle we. Physically build a machine that 782 00:36:14,320 --> 00:36:19,040 tilts the sample tube to exactly 54.74° relative to the main 783 00:36:19,040 --> 00:36:21,200 magnetic field, and then we spin it. 784 00:36:21,400 --> 00:36:23,280 How fast are? We talking fast. 785 00:36:23,760 --> 00:36:25,600 Very, very fast. We're talking about spinning in 786 00:36:25,600 --> 00:36:29,520 the kHz range, so 10,020 thousand, sometimes up to 787 00:36:29,520 --> 00:36:32,240 100,000 rotations per second. That's faster. 788 00:36:32,240 --> 00:36:34,240 Than a jet engine turbine much? Faster. 789 00:36:34,240 --> 00:36:37,000 The rule of thumb is that your rotation speed has to be faster 790 00:36:37,000 --> 00:36:39,000 than the magnitude of the interaction you're trying to 791 00:36:39,000 --> 00:36:42,200 average away, so you spin. This tiny tube at 10s of 792 00:36:42,200 --> 00:36:46,240 thousands of RPMS at a perfect 54° tilt and when you. 793 00:36:46,240 --> 00:36:48,720 Do that. You are mechanically forcing the 794 00:36:48,720 --> 00:36:52,400 time average of that pesky 3 coast term to become zero. 795 00:36:52,800 --> 00:36:55,400 To the nucleus it looks like it's tumbling isotropically. 796 00:36:55,400 --> 00:36:57,520 The solid thinks it's a liquid that. 797 00:36:57,520 --> 00:37:00,560 Is essentially hacking the laws of physics, you're saying? 798 00:37:00,920 --> 00:37:03,040 I don't like this term in the equation, so I'm going to 799 00:37:03,040 --> 00:37:06,960 physically engineer a device to rotate my entire sample to 800 00:37:06,960 --> 00:37:08,800 mathematically delete it. That is exactly. 801 00:37:08,800 --> 00:37:11,360 What we're doing and the result is absolutely stunning. 802 00:37:11,560 --> 00:37:16,000 The broad ugly blobs collapse. The featureless smears sharpen 803 00:37:16,000 --> 00:37:18,240 up into distinct high resolution peaks. 804 00:37:18,240 --> 00:37:20,200 The notes have a. Great example they do. 805 00:37:20,480 --> 00:37:23,480 A comparison of the spectrum of tyrosine, which is an amino 806 00:37:23,480 --> 00:37:26,280 acid. Without mas, the solid sample 807 00:37:26,280 --> 00:37:29,120 gives you a lumpy, useless hill. You can't see anything. 808 00:37:29,280 --> 00:37:34,080 Turn on mas and you can see a clear, resolved peak for every 809 00:37:34,080 --> 00:37:36,320 single carbon atom in the molecule. 810 00:37:36,600 --> 00:37:37,480 It's night and. Day. 811 00:37:38,040 --> 00:37:40,080 But even with magic angle spinning we still have that 812 00:37:40,080 --> 00:37:43,560 sensitivity issue right? Remember carbon 13 is rare and 813 00:37:43,560 --> 00:37:46,000 it's also lazy. Lazy. 814 00:37:46,000 --> 00:37:50,000 Is a very good word for it. In NMR terms, it has a very long 815 00:37:50,000 --> 00:37:53,800 spin lattice relaxation time, which we call T1, meaning it 816 00:37:53,800 --> 00:37:55,480 takes a. Very long time for it to reset 817 00:37:55,480 --> 00:37:57,320 after you hit it with a pulse. A very long. 818 00:37:57,320 --> 00:37:58,920 Time. After you hit it with that 90° 819 00:37:58,920 --> 00:38:02,200 pulse, it takes a long time for it to relax back to its 820 00:38:02,240 --> 00:38:04,840 equilibrium state, so you can pulse it again and collect more 821 00:38:04,840 --> 00:38:07,640 signal. For some solids, this T1 can be 822 00:38:07,640 --> 00:38:11,120 minute or even hours. So if you need to accumulate 823 00:38:11,120 --> 00:38:14,080 thousands of scans to see the weak signal, and you have to 824 00:38:14,080 --> 00:38:16,720 wait 5 minutes between each and every scan, you'd be there for. 825 00:38:16,720 --> 00:38:18,520 Weeks, the experiment becomes impossible. 826 00:38:18,520 --> 00:38:19,920 It's completely. Impractical. 827 00:38:19,920 --> 00:38:21,960 So we use the protons again, they're our friends. 828 00:38:22,360 --> 00:38:24,920 This brings us to the second major technique, cross 829 00:38:24,920 --> 00:38:27,480 polarization or CP. OK, how does? 830 00:38:27,480 --> 00:38:29,160 That work protons are. Abundant. 831 00:38:29,320 --> 00:38:31,640 They're sensitive and they relax very quickly. 832 00:38:31,640 --> 00:38:35,520 They're energetic, so we use a clever sequence of 833 00:38:35,520 --> 00:38:39,600 radiofrequency pulses to create a condition where the protons 834 00:38:39,600 --> 00:38:43,280 can transfer their polarization over to the carbons. 835 00:38:43,280 --> 00:38:45,160 We're stealing the. Energy from the protons and 836 00:38:45,160 --> 00:38:48,080 giving it to the carbons we are. We're essentially pumping the 837 00:38:48,080 --> 00:38:51,920 signal from the abundant energetic protons into the rare 838 00:38:51,920 --> 00:38:54,640 lazy carbons. It's like a blood transfusion 839 00:38:54,640 --> 00:38:58,080 for the signal, or giving the carbons battery a jump start 840 00:38:58,080 --> 00:39:00,000 from the protons battery. And what does? 841 00:39:00,000 --> 00:39:02,120 That do for us practically 2 huge. 842 00:39:02,120 --> 00:39:05,800 Things first, the carbon signal gets significantly stronger. 843 00:39:05,800 --> 00:39:07,640 It's an enhancement of its sensitivity. 844 00:39:08,000 --> 00:39:11,240 And 2nd, and maybe even more importantly, we no longer have 845 00:39:11,240 --> 00:39:13,440 to wait for the carbon to relax. We only have to. 846 00:39:13,440 --> 00:39:15,480 Wait for the protons to relax. Exactly. 847 00:39:15,480 --> 00:39:18,640 And the protons relaxation time is short, maybe a few seconds, 848 00:39:18,840 --> 00:39:21,840 so we can pulse and scan much much faster. 849 00:39:22,160 --> 00:39:25,320 An experiment that would have taken a week can now be done in 850 00:39:25,320 --> 00:39:26,280 an hour. And. 851 00:39:26,280 --> 00:39:28,840 Finally, the notes mention one more piece to the puzzle. 852 00:39:29,800 --> 00:39:32,040 Depolar decoupling. That's the third. 853 00:39:32,040 --> 00:39:34,960 Leg of the stool. Even with MAS spinning, those 854 00:39:34,960 --> 00:39:38,960 powerful dipolar interactions between protons and carbons can 855 00:39:38,960 --> 00:39:41,320 still cause a little bit of broadening, so you need to get. 856 00:39:41,320 --> 00:39:42,280 Rid of them. We need to shut. 857 00:39:42,280 --> 00:39:44,480 Them up. So while we are listening for 858 00:39:44,480 --> 00:39:47,480 the carbon signal to come back to us, we blast the protons with 859 00:39:47,480 --> 00:39:50,600 a continuous high power radio frequency signal. 860 00:39:50,600 --> 00:39:52,640 What does that do? To the protons it forces. 861 00:39:52,640 --> 00:39:55,800 Them to flip their spins back and forth, up and down so 862 00:39:55,800 --> 00:39:58,600 rapidly that the carbon just sees an average. 863 00:39:58,680 --> 00:40:01,440 It sees a blur. It effectively cuts the magnetic 864 00:40:01,440 --> 00:40:04,840 communication line between them. It decouples them so to. 865 00:40:04,840 --> 00:40:09,080 Get a really good picture of a solid polymer like the PMA 866 00:40:09,080 --> 00:40:12,560 example, the polymetal methachrylate in the notes. 867 00:40:12,760 --> 00:40:15,000 You you have to combine all three of these things at once. 868 00:40:15,040 --> 00:40:16,840 You have to. And the notes show this 869 00:40:16,840 --> 00:40:18,840 beautiful progression that's worth walking through. 870 00:40:19,000 --> 00:40:21,840 Let's do it. Step a a static sample, No 871 00:40:21,840 --> 00:40:25,920 spinning, no nothing. And the spectrum is basically a 872 00:40:25,920 --> 00:40:28,160 flat line with some noise. You see nothing at all 873 00:40:28,160 --> 00:40:29,960 completely. Useless step B. 874 00:40:30,280 --> 00:40:33,760 Now you keep it static, but you turn on cross polarization. 875 00:40:34,080 --> 00:40:36,600 Now you see a big broad undefined bump. 876 00:40:36,600 --> 00:40:39,200 You have signal, but you have 0 resolution. 877 00:40:39,200 --> 00:40:40,720 It's just a mountain. Better than nothing. 878 00:40:40,720 --> 00:40:44,200 But still a BLOB step C. Now let's turn on Magic Angle 879 00:40:44,200 --> 00:40:46,360 Spinning. The bump immediately starts to 880 00:40:46,360 --> 00:40:48,840 split into a few broad but distinct peaks. 881 00:40:49,000 --> 00:40:51,560 You can see shapes starting to emerge from the noise. 882 00:40:51,560 --> 00:40:52,360 OK, we're getting. Warm. 883 00:40:52,360 --> 00:40:54,000 We're getting somewhere. And finally. 884 00:40:54,000 --> 00:40:58,200 Step D You combine everything, magic angle spinning plus cross 885 00:40:58,200 --> 00:41:02,400 polarization plus high-powered decoupling and suddenly crystal 886 00:41:02,400 --> 00:41:05,760 clear sharp peaks. You can now identify the 887 00:41:05,760 --> 00:41:10,080 individual carbon atoms methyl group, the chapter 2 group, the 888 00:41:10,080 --> 00:41:11,880 carbonyl Co group you've gone from. 889 00:41:11,880 --> 00:41:15,600 A flat deadline to a precise molecular fingerprint of the 890 00:41:15,600 --> 00:41:16,840 polymer. That is the power. 891 00:41:16,840 --> 00:41:19,560 Of modern solid-state NMR. It allows us to look inside 892 00:41:19,560 --> 00:41:22,120 materials that were previously just a black box. 893 00:41:22,360 --> 00:41:24,760 We can see the structure of plastics, of biological 894 00:41:24,760 --> 00:41:27,680 membranes, of batteries while they're operating, of industrial 895 00:41:27,680 --> 00:41:30,480 catalysts, all these things that simply cannot be dissolved. 896 00:41:30,560 --> 00:41:31,560 It's just. Incredible. 897 00:41:31,720 --> 00:41:35,200 We've really traveled from the quantum spin of a single proton 898 00:41:35,480 --> 00:41:38,480 through these giant superconducting magnets all the 899 00:41:38,480 --> 00:41:43,400 way to spinning samples at 54.74° just to cheat the math it 900 00:41:43,400 --> 00:41:45,080 really. Highlights the philosophy of 901 00:41:45,080 --> 00:41:48,200 structural chemistry that was mentioned on the very last slide 902 00:41:48,200 --> 00:41:49,960 of the source material. Which is what? 903 00:41:50,040 --> 00:41:52,120 It's that. No single method tells you 904 00:41:52,160 --> 00:41:54,880 everything. The notes really emphasize this 905 00:41:54,880 --> 00:41:57,080 point. The course philosophy is to 906 00:41:57,080 --> 00:42:00,480 solve structures by combining multiple techniques, right? 907 00:42:00,480 --> 00:42:04,040 Sometimes you need solution and Mr. Sometimes you need 908 00:42:04,040 --> 00:42:06,880 solid-state NMR. Sometimes you need to look at 909 00:42:06,880 --> 00:42:09,440 coupling constants to figure out the geometry. 910 00:42:09,880 --> 00:42:12,120 Other times you need a completely different technique 911 00:42:12,280 --> 00:42:15,640 like X-ray diffraction or mass spectrometry. 912 00:42:15,640 --> 00:42:17,920 You have to be A. Detective who uses every tool in 913 00:42:17,920 --> 00:42:20,720 the kit. A single method is powerful, but 914 00:42:20,720 --> 00:42:23,640 it's by combining them that you really solve the puzzle exactly. 915 00:42:23,800 --> 00:42:25,840 Each one gives you a different piece of the story. 916 00:42:26,040 --> 00:42:26,960 That's a great. Take away. 917 00:42:26,960 --> 00:42:30,000 But before we wrap up, I want to leave our listeners with a final 918 00:42:30,000 --> 00:42:32,200 thought that really struck me while I was reading through all 919 00:42:32,200 --> 00:42:36,000 this. We spent this whole hour talking 920 00:42:36,000 --> 00:42:39,640 about the active nuclei, the ones that have spin, the ones 921 00:42:39,640 --> 00:42:42,080 that talk to us, the protons. The carbon thirteens, the 922 00:42:42,080 --> 00:42:44,680 phosphorus 30 ones, the. Spies. 923 00:42:45,120 --> 00:42:47,200 But remember at the very beginning we talked about the 924 00:42:47,200 --> 00:42:51,040 silent majority. Carbon 12, Oxygen 16. 925 00:42:51,120 --> 00:42:53,680 The ones with. Even protons and even neutrons 926 00:42:53,680 --> 00:42:56,440 and these atoms. Make up the absolute bulk of 927 00:42:56,440 --> 00:43:00,040 organic existence our bodies, the trees outside this building, 928 00:43:00,040 --> 00:43:02,960 the plastic in your phone structurally, they're mostly 929 00:43:02,960 --> 00:43:05,600 built from atoms that are completely invisible to this 930 00:43:05,600 --> 00:43:08,000 incredibly powerful machine it is a very. 931 00:43:08,000 --> 00:43:10,480 Humbling thought. We are building these incredibly 932 00:43:10,480 --> 00:43:15,280 detailed, beautiful 3D models of reality, but we are doing it by 933 00:43:15,280 --> 00:43:18,040 listening to the 1% of the carbon atoms that happen to have 934 00:43:18,040 --> 00:43:20,240 an odd number of neutrons we're ignoring. 935 00:43:20,240 --> 00:43:22,600 The other nine 9% that are silent, we are. 936 00:43:22,600 --> 00:43:25,720 We're inferring the entire structure from a very small, 937 00:43:25,720 --> 00:43:28,080 select group of reporters. Exactly. 938 00:43:28,560 --> 00:43:31,840 We are trying to understand the shape of an elephant by 939 00:43:31,840 --> 00:43:35,400 listening to the fleas that are living on its back and it just 940 00:43:35,400 --> 00:43:39,640 makes you wonder what subtleties of structure, what dynamics are 941 00:43:39,640 --> 00:43:43,320 we missing because we can only hear the loud neighbors that is 942 00:43:43,320 --> 00:43:45,040 the. Perpetual question of science, 943 00:43:45,040 --> 00:43:46,480 isn't it? We can only see the world 944 00:43:46,480 --> 00:43:50,000 through the tools that we have, but as we saw today with Magic 945 00:43:50,000 --> 00:43:52,920 angle spinning, sometimes when you can't see something clearly, 946 00:43:52,920 --> 00:43:55,560 you just have to spin your perspective a little bit on that 947 00:43:55,560 --> 00:43:57,440 note. Thank you for joining us on this 948 00:43:57,440 --> 00:43:59,720 deep dive into the magnetic world of NMR. 949 00:43:59,720 --> 00:44:01,680 It was a real. Pleasure keep spinning. 950 00:44:01,680 --> 00:44:04,360 Keep questioning and we'll catch you in the next deep dive.