Transcript for:
Lecture on Electrophilicity, ATP, and Alcohol Metabolism

we are live all right before we begin chapter five we are going to go over this old uh Little Riddle that I had up for you guys and I said that this is the list of carboxilic acid derivatives in order of what in order of increasing electrophilicity right increasing electrophilicity and if they increasing electrophilicity that means that this carbon this carbon this carbon this carbon this carbon this carbon this carbon as you go up is more susceptible to attack by a nucleophile right now the thing is when that gets attacked in a normal like let's say it's lvg right here I wonder why I'm calling it lvg right when that gets attacked by a base something like this happens so you get electrons kick up and eventually electrons kick back down and kick off the leaving group right so the the forward nature of the reaction is dependent upon two things number one how stable is that but more importantly how stable is this right how stable is that because that is a conjugate base and we talked about acid and base stability in our earlier lectures so if we're able to predict the stability of a leing group off of these then we would be able to say hey I understand why that reaction goes that way and why the electrophilicity presents itself like it does here so let's take a look let's take a gander right and instead of using a specific molecule instead of using a specific thing we're going to use a base B that is just strong enough to perform the reaction for these it's very easy for these it gets more difficult right so let's take a look first at the acid chloride a base B will come and attack here and kick this up B oxide CL oxide comes down and kicks this off this is also known as the tetrahedr carbonal addition intermediate and that will form o b and cl minus CL minus good conjugate base or bad conjugate base very good very very good and how do we know that well we know that it's quite electr negative it's quite large right it's an annion it doesn't mind accommodating that it it's completely stable with eight electrons around it right but we also know from the pka table I gave you that the conjugate acid pka is what what's the conjugate acid pka of HCL some you can go back go back look at your notes what's the conjugate acid pka of HCL sorry or like what's the what's the pka of HCL NE five right so HCL has A5 PKA and that's reflective of the stability of Cl minus what's good low PKA or high PKA low PKA is good that means this is really really stable right because low PKA means very high acidity which means very good or very low basicity so is this going to come back and attack here no so CL minus fantastic leaving group and what I'm going to do right here is write conjugate acid pka equals five what about the anhydride all right some base B will come and attack here tetrahedr carbonal addition intermediate o minus B transition yields resonance stabilized very nice not as good as chloride right because it's on oxygen but it is resonant stabilized and that's pretty good and what is this this is just r o or like this is just R Co minus what did I tell you the pka was of carboxilic acids or Co this is one that I left out the first time so it might not be in your notes four to five yeah PKA four to five C A PKA equals 4: 5 all right ready oh one more thing I think I forgot to mention is that when you have like f CL BR I the reason F like if if it's F minus it's HF right like HF HCL hbr I the reason this is three and this one goes to5 also not just the size but also access to the D orbital the D orbital gives you a lot more room right inside of that atom you guys get what I'm talking about two three period two period three period three you unlock the D orbital right cool the D orbital is really important really important okay biester some base B that's capable of Performing the reaction theoretical base B I'm not going to draw out the whole thing anymore you guys get the gist you make the O minus it comes back down right we get what is the pka of HSR eight not as good as oxygen actually larger than oxygen but not resonant stabilized so not as good as the carboxilate right here all right what's next these two are really interchangeable these two right here so these two can go here and go here right okay some base B that's capable of Performing the reaction performs the reaction and we get b o r minus what's the conjugate what's the conjugate acid pka what's the pka of R 16 to 18 and here if we kick off o minus it'd be 15.7 so I guess this one goes up there so CA PKA 15.7 CA PKA 16 to 18 all right one last one some base some wildly strong base that is capable of Performing this reaction kicks off nh2 what's the conjugate acid pka what's the PK of NH3 385 4 to 5 8 15.7 16 to 18 38 and impossible to kick off this is not possible you can't kick that off because you would have to make a double negative oxygen that's not going to happen not at least not with our organic chemistry materials right so you see that as the electrophilicity goes up the conjugate acid pka of the leaving group decreases which makes sense which makes complete sense because the conjugate acid pka reflects the acidity of that acid the preferential formation of that leaving group how preferable is making that leaving group that we kicked off and what you guys probably realized while I was writing all this down is that the leaving group is just whatever is left after you cut this and cut this and cut that and cut that and cut that and cut that those are your leaving groups do you guys Now understand why the electrophilicity goes like that okay but that's not the only thing we want to learn here that's not the only thing we want to learn I'm about to blow your mind blow your mind I'm going to explode your brain into 10 million pieces ATP you know what I erase this first because it's gonna blow your mind even more if I erase this ATP yields [Music] ADP and pi and what else what else energy energy all right I always forget how to draw a Denine okay so we got I need to bring this closer to me so we got this guy nope I'm gonna do it that way nope I'm gonna do it this way we got this guy and then we have an N that and we come down got another nitrogen we go up we got a ring double bond n drop N double bond drop NH H2 and that is a Denine and disconnects to your ribos and it's smooth salent from here okay ATP when we break ATP and we turn into ADP you see how this is the adenosine and this is the triphosphate because what is a Denine it's adenine with a ribos sugar adenine ribos right weot a double bond in the middle adenine ribos right when we break this triphosphate we use usually hydrolysis right so what happens is that we add water into this and this phosphate known as the gamma phosphate the gamma phosphate why is it called the gamma phosphate because this is the Alpha Beta wait no it's called the get I forgot how to number it I think this is the AL Alpha Beta Delta gamma position so it's like there off the carbon something I don't know it's called the gamma phosphate whatever this phosphate this third phosphate gets kicked off and now when that happens I want to show you something so this is the structure right and now I'm going to erase it so that you guys know where we're oriented and I'm going to show you something everything other than that on that structure I'm going to call R so we have this and I'm going to draw it correct according to orgo so this is the gamma phosphate connected to its partner the phosphate that's next to it you guys ready to see the magic can you already see the magic an it's a phosphor anhydride right so when the water comes in or the glucose comes in or whatever comes in and comes attacks this phosphorus we kick up and we come back down and we kick this off and what did we just do if we get rid of the water and we get get rid of the arrows basically what we're doing is we're taking this Bond right here this Bond right here between this phosphorus and this phosphorus and we're chopping it and we're putting an O over here and an H over there and what bond is that analogous to it's analogous to this bond that bond that just got broken so now we have effectively kicked off this but in phosphate form right and if we've kicked that off in phosphate form it's not going to be H because there's an R over there we need two negatives on a phosphate at neutral pH if we've kicked that off we allow this to resonate now number one number one that's allowed to resonate and number two those two phosphates that were both negative and really tightly packed to one another can now repel one another and that's called charge separation and like charge separation is a very stabilizing effect right if you take two positive magns you put them together it will repel like this you think that's good or bad that's good right and how much energy does it take to push two magnets together like this it takes a lot of energy right so allowing them to separate would release energy so you get a release of energy the energy harnessed by ATP is through the hydrolysis of a phosphor anhydride bond and through the separation of like charges has your mind been blown good that is how ATP produces energy that is how ATP produces energy right and the other thing this is going to blow your mind even more is that sometimes we start trading we start playing trading cards right so here is suo COA suo COA and in the citric acid cycle suino COA is turned into succinate and they just tell you that the enzyme sus inil a synthetase takes a GDP and turns it into a GTP how well as you can see by our diagram the anhydride and the thioester are very close together on the chart right so if you cut a thioester bond the energy released from there might just be enough to form an anhydride Bond isn't that wild we couple these These are called coupled reactions we couple the cleavage of a diester to the synthesis of a phosphor and hydde coupled reactions yeah are do you guys follow are you sufficiently impressed with the science not with me with the science good cuz this is listen everyone always tells me like some of my students they always tell me like oh my God like you're so cool like you know all this stuff and you like just say it blah blah blah I like guys someone should have taught you this someone should have given this to you it's it's not like some miracle that I'm giving you this this is literally like what did I just exp think about what I just explained to you you've been learning since you were 13 12 years old that ATP makes energy how old are you that you learned how it happens someone should have taught you this this is not miraculous this is not me giving you a gift this is me picking up the slack of other people this is not a miracle this is stuff you guys have to know and once you know it everything becomes a lot more sensible okay good so I I'm I'm not some miracle worker I'm some guy filling in the gaps guys I want to talk about alcohol all right chapter five alcohols yeah what's up I untrue untrue un true sugars are not alcohols sugars are not alcohols phenols not an alcohol actually no phenol is an alcohol sorry but phenol is an alcohol but like I said phenol I was thinking about this thing this is 24 dnp I will find you hard pressed to tell me that that's an alcohol also wait what the what about your proteins like what about like all of your proteins with cysteine in them there's not cysteine sorry Serene in them thine in them right like what what about water was like yeah but like it's it's just you know and then start asking yeah that's like the whole like what makes something organic type of thing thing yeah right I think it's just carbons and hydrogens that's that's always been my thing oh by the way before we start alcohol sorry forgot to mention something one two three one 2 three four five bonds right why because it's a 3p element has access to the D orbital it can accommodate those bonds right but but but understand this in order to do that chemistry that we did to it in order to do that attack and everything on the double bond what's the shape of this it has to be tetrahedral it must because you have to be tetrahedral in order for that to happen why is it tetrahedral because the electron geometry is tetrahedral 1 2 3 4 means your electron geometry is tetrahedral if it had a fifth electron domain right there it would no longer be tetrahedral okay alcohols um there are some PKA considerations by Kaplan but it's stuff we've already talked about like how the inductive effect lowers the pka and resonance lowers the pka and a larger Al alcohol has a higher PKA than a smaller alcohol because it's like less stable as the base and it doesn't get solvated as well so let's talk about that for one second why does this have a greater PKA than this well it's because when they both turn into conjugate bases like it's easier to surround this with other molecules of aloh than it is to surround this right solvent effects right stabilization okay uh reactions of alcohols okay we're going to list off some reactions you have to know and you have to know them by heart number one how do you take an alcohol how do you take a primary alcohol and turn it into an alahh PCC what does PCC stand for please create carbonal please create carbonal and nothing else I think it's like a Poison Jones reagent [Music] um yeah it's it's purine chromal chloride or some like that um Let me let me look up the proper name for you uh peridinium chlorochromate is PCC but it's please create carbonal right all right PCC uh and then oxidation with Jones reagent right so let's talk about Jones reagent number two this is going to be your secondary alcohol and you're going to see it two ways you're going to see N2 cr207 right or and h204 or you're going to see or you're going to see C3 h2so4 and acetone both of these are the same thing Jones reent Jones reagent right to secondary Al it's going to turn into a ketone to Prim alcohols it's going to turn into a carboxilic acid it will take it as far as it can possibly go sorry that is not very clear this says acetone acetone can you drink acetone don't you you could you could and the reason I say you could is because acetone is produced in really small amounts in your body when you have katsis acetone is a ketone body don't drink acetone although it smells really good in my opinion really mm I love the smell of acetone GL I love the smell of glue I love the smell of gasoline I love the smell of sharpies love isopropyl oh isopropyl alcohol smells so good I think that's why I'm I think that's why I'm like this cuz cuz as a kid I was just like oh gasoline don't Huff gas don't do not Huff gas that is so bad for you like I as much as I joke about it huffing gasoline like even for if all you breathe is gasoline Vapors for like 5 Seconds you will cause permanent brain de damage it's fine if you're at a gas station because there's still air around you but there are many many many horror stories on the internet of people putting their noses inside of gasoline canisters and permanently damaging themselves why because gasoline is 1 2 3 4 5 6 S 8 Octane and octane is really non-polar which makes it what hydrophilic or lipophilic lipophilic because some fats in your body just look like this really similar to gasoline where if you just take this away they're pretty much the same so gasoline will dissolve itself inside of fats in your body you know it has a lot of fat in your body your brain your brain is really really really dense in fat right so when you have anything that's lipophilic and really non-polar it if it can cross the blood brain barrier it'll just situate itself and get really comfy in your brain what's another lipophilic molecule that people encounter all the time especially in New York City THC if you smoke weed for a very very long time it'll settle itself into your atap POS tissue and then later if you fast for a very long time or you work out very strenuously it's possible to start burning fat and releasing THC back into your bloodstream so you can get a really really really faint high from working out because it's the THC releasing itself from your fat cells happened one of my buddies once or at least he said or at least he said it happened huh is that is THC bad I don't know I don't smoke take take that as my answer to your question I don't smoke and I would not smoke if I were you huh I've had runers high before I've had runers high like three times it is it is definitely real and it's the closest thing you can feel to like ascending it is unreal my my story with runner's high I was I was sick as a dog I was really sick running this race had Wicked sinusitis could barely breathe the whole time I'm two miles into a 5K race so I have 1.1 miles to go and I'm in so much pain and all my muscles ache because if you've ever had sinusitis it causes your whole body to just like sh shut down like it's really bad so my muscles ache I can't really breathe all that well and all of a sudden I feel like someone took a cold knife and just cut through my neck right and all I felt was starting from my neck moving down this warmth this really really warm feeling and it just radiated down my entire body and like when I'm running I always have something going on in my head and I realized the moment that happened my brain just shut off my eyes got super wide like I felt them and my whole Airway just cleared and for the next 1.1 miles I swear to I don't even remember what happened all I remember was one foot after the other after the other after the other after the other after that's all I remember and I crossed the Finish Line I stopped I stopped running and I collapsed and threw up but those couple minutes running that one mile were some of the greatest moments of my entire it was UNF freaking believable I would do anything anything to feel like that again shrooms I would not do shrooms you I will stick to my 15 Mile runs I I actually like the reason I part of the reason that I try to go really longdistance running in summers to feel that again I swear to you I swear it's because I want to feel like that again without significantly damaging my health all right uh reactions of phenols right so this is whatever and then we talked before about the important reaction if we take a hydroquinone and we oxidize it normally with Jones reagent as well or in your body with other things right we can make oops sorry that's a big orgo no no we can make a quinone right um this comes up like once in a blue moon on the MCAT right so it's helpful to know is that if you take an alcohol and you put it in a a solution of tossel chloride and purine the tossel chloride which looks like this it's talline and like a sulfur chloride group right that's toine then you attach a little that to it basically what you can do is you can attack here because that's tetrahedral and you can get the same thing going on like that and what you'll make after you deprotonate the alcohol and what are you deprotonating with you're deprotonating with paradine what is paradine it's uh that guy paradine right it will make peridinium you're deprotonating with that what are you deprotonating that guy after it picks up the tosilate right you will make OTS or o s o o tosel or this is also known as OTS oats and and that is a way of creating a good leaving group right from an alcohol and why is that a good leaving group because imagine you guys are cerebral enough to see this now if this left with its electrons this can resonate into those can it resonate into the Benzene ring why not that's SP2 well let's see let's let's take a look actually cuz this this is one of the things you got to draw out oops all right so these come down and what if this guy goes up well what if this guy just goes over you can't do that so no it cannot resonate in the Benzene ring I don't think it can because what if we because if we go like that actually no it can yeah there you go so it can yeah wait no it can't because you're hopping the sulfur because like the the big thing here is that you're maintaining the same number of bonds here as well right so if this comes down you'd have to break that Bond over there so I don't think you can I just think you'd overwhelm the the sulfur in the middle I got I got to do more work on that I got to look at it like for a while and try to figure it out but doesn't matter it's good leaving group because it can actually resonate up there as well right good leaving group from an alcohol so that's the mechanism going to erase the mechanism just to make more room see I'm learning along with you guys and that's what I like about teaching um that's it yeah that's it that's the entire alcohol chapter basically it's these five reactions and we're going to build on it further and further but while we're here let me give my biocham people a pep talk all right who here has taken biocham or likes biocham or has an interest in biocham hands up cool all right we talked previously about alcohol metabolism and how alcohol metabolism works it is a two-step process by which you turn alcohol into vinegar in your body you basically turn alcohol into vinegar so when you drink alcohol what are you drinking you're drinking ethanol right ethanol in your body you have an enzyme called alcohol dehydrogenase and dehydrogen enzymes are for oxidations and reductions in this case it's for oxidations right it will use NAD NAD will get reduced into nadh and H+ and it will turn the alcohol into a what is this what is this an alahh right what is the name of that alahh this is ethanol that's Ethan ethanal right ethanal but it also has another name it's called acid alahh where did this asset come from where else do we see that AIC acid acetate it means two two carbons acid alide and acid alide will undergo another oxidation by acid alide dehydrogenase and a D nadh and H+ makes acetic acid which can be urinated out of the body okay good yeah so when you drink alcohol you can see that it kind of depletes your NAD stores right it uses up a lot of the NAD and H my shirt was sticking out and when that NAD gets used up it makes nadh and sometimes that nadh can leak out and go other places and it can start hooking up with other people right that's what NAD that's what NAD and nadh do they just hook up with whoever they can and sometimes when you're a human who loves to perform metabolism you make this little acid in your body called pyruvic acid or pyate right pyate hold on don't get ahead of yourself one sec just closing this off so have pyate it's my mother again so you have pyate and sometimes pyate can encounter an DH and nadh can dump its electrons on pyate and reform nad+ because we want to balance we always want to balance between NAD and NAD plus and nadh because that allows us to control rates of metabolism in different parts of the body the NAD plus to nadh ratio right we're going to talk a lot about that when we talk about carbohydrate metabolism and fat metabolism and the pentos phosph pathway blah blah right talk a lot about that also someone to look forward in biocam I will finally tell you the difference between nad+ and nadp+ I will tell you the difference and why we have two of them even though they do the same thing stick around also guys we sticking around tell your friends about my lecture if you haven't already let's get some more heads in here because when we do biochem trust a lot of people will want to attend those lectures so pyate can stick can hook up with nadh right and nadh has electrons now right it's oxidized alcohol and now has electrons and it can make what from py well if we reduce it we're going to reduce it here and if you guys don't know what that is that's lactate that's a lactate so sometimes drinking s Superfluous amounts of ethanol can give you lactic acidosis means your blood becomes acidic lactic acidosis lactic acidosis is very bad very bad very bad you will learn about it in medical school don't say I didn't warn you all right so that is pyrovate to lactate right and we're going to talk a lot about that in the lactic acid cycle this can also be induced by strenuous exercise but when it's done by exercise our body normally has a way of combating that right but when people say oh my muscles s lactic acid they're not wrong it is part of what's going on right one more thing that's cool about alcohol metabolism I told you guys about Asian glow when Asian people or people of Eastern Asian or Southeast Asian descent drink alcohol they may get red in the face right and it's because within that region of the world and in their genetic makeup they have a relative deficiency of acid aldhy dehydrogenase and acid alahh is very toxic to your body but when you drink alcohol you don't make enough of it to kill you unless you drink a ton of alcohol right but you do make enough of it for it to get through your bloodstream and cause flushing Vaso dilation in the face and that Vaso dilation leads you to be hot and flush so if you have a relative deficiency of that you're going to perform less of this you're going get an accumulation of acid aldah and that acid alide is going to move through your blood and you will get flushing and you also get nauseous and you also get a headache and you also get muscle Flakes and you'll also have light sensitivity what am I describing here a hangover this is The Hangover that guy that's the hangover acid Alid is The Hangover alahh eyeses are if you're going to remember something for biocham alahh eyeses are really really really toxic they're really bad for you do I drink no I don't okay 813 let's see what's next because honestly I would not mind just completely ripping through orgo you guys want to do the next chapter it's really short maybe like 20 30 minutes and then we'll go home yep all right uh let's make a new video cuz we did the carboxilic acid stuff and then we did the alcohol so let's do chapter six in the next video see you next time