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Lecture 03. Reactivity and Arrow Pushing.

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welcome to Week 2 of chemistry 128 introduction to chemical biology on Professor Weiss all be talking to you today about the reactivity but it's the last week we talked about the molecules that compose yourselves and our goal this week is to understand how these molecules interact with each other there are 2 forms of this interaction the 1st
kind is that the molecules can decide to react with each other they can only start to form covalent bonds bonds can break bonds conform so we want to understand this property that we're going to call the reactivity and to understand us were going to look at heroes and the language of Eros which organic chemists have developed as a way of communicating this reactivity I have to tell you
I think that this is from 1 of the great achievements of organic chemistry this is on 1 of those accomplishments that all humans can be proud of because it reduces something that otherwise seems mysterious to a simple set of rules from which you can derive many many reactions essentially all reactions found on our planet and to me that's really exciting because that uh that means that this language is universal and it's 1 that's very broadly applicable and so on that's that's my bias going as I think this is really cool OK I'm sorry to have a quick review of the operation and then I'm going to show you examples of applying this language of error pushing and this language of reactivity in chemistry too the chemistry that's found in on our planet before life started this is the type
of chemistry call people a chemistry now obviously the renewed humans present to observe directly what was going on however we can infer what was going on in this prebiotic period this is an artist's conception of what the planet might have looked like on for both the fossil record and also from experiments that attempt to recreate the conditions that were found during nap prebiotic period K so long we're going to be using what we learned to really to look at us at the center of the molecules that comprise that cell and then the next topic will talk about this week is on me making molecules using a combinatorial approach this is essential in commodity chemical biology this ,comma tore up her approach takes place
in your cells it's 1 of the reasons why you're immune system can very rapidly respond to foreign invaders and also is used in many chemical biology laboratories around the world and so for this reason I have to introduce this concept of common Tyrrell chemistry ,comma tour biology to you this way and then finally will look at the 2nd mode of of molecules interacting with
each other recalled the start of this said there were 2 roads the 1st note being the activity that forms covalent reactions that results in covalent changes barnstorming in breaking this
2nd know is non-covalent interactions misses when 2 molecules slide alongside each other and decide to form a complex with each other and the rules that determine whether or not this complex forms are also rules that we can understand and and importantly this is also a really tough frontier for chemical biology so while appealed to tell you about the rules for reactivity covalent bond breaking in bond forming a recovery actions I cannot reply with such certainty when we start talking about non-covalent interactions there's a lot less that we understand and that makes it 1 of 1 of the challenges but this in time it also makes it really exciting because is that means there's opportunities for people like yourself to get out and a new experiments to start to elucidate those types of rules OK so I have some announcements before we go and that's kind of the overview let's sizing down look at the particulars from 1st of 4 this weekend like you to read Chapter Two in the textbook so that this book here but now
this uh occasional times were the treatment in textbook is more advanced than when I'm talking to you about it for example there's
information about an inversion of phosphate geometry of phosphorus geometry I'm not going to discuss that if I don't discuss it in the lecture then don't get too hung up on him in the book cases simply skim the concepts that are not presented in lecture testified talk about a lecture it's not important for the class in terms of our exams and 1 of the testing your simply skim through some homework I'd like you to work checked 2 problems in particular every odd problem and there will be a worksheet to guide our our discussions this week which will be posted to the class website In addition there will be 1 hand out this week which we posters of course website please download this on Tuesday to see him through it this handout is an example of a journal article report of which are used to call a book report and then on Thursday all discussed it with you in further because of at this point I would usually ask if you have any questions if you do have questions and you can either e-mail me or the tears
OK so let's review worried then and get started on what I told you about the beginning as big picture so we want to understand the function of human cells at the level of Adams and bonds this is the
smallest unit that actually is meaningful to us as chemists and on as I described to you last week sales are bad of molecules in their bags they're chock-full of molecules the molecules are stuffed inside the cells there's no elbow room these things are GM packed into the cell so because of that we expect lots and lots of interactions which is a topic for this week but I'm getting ahead of myself when we continue reviewing what we talked about the previously on 1st we talked about the composition of achievement as an ostrich with instructions we talked about the House is how molecules the synthesized in the cell using the template of DNA To a messenger RNA which then is translated into proteins and the proteins and on a composed carry out all the various instructions that are articulated by the but we
also discussed 6 types of organisms but in this class we're going to be generally talking about you the bacteria were human cells and it turns
out there's a lot of chemistry in just bacteria human cells so our goal in this week is to reduce the complexity of diagrams like this down to I'm a few rules that are chemists like ourselves could understand OK so let's get started with what his life was the stuff What are the molecules that compose sells what are the rules that govern them in I'm 1948 that physicists are injured in Erwin Schrödinger wrote a very influential book called What Is Life I highly recommend this book to it's a slim little volume and it's a fun read it's not particularly challenging but the concept said he % but to you are really earth-shattering these are paradigm changing weather Schrödinger argue is that the molecules that govern yourselves that allow organisms like yourself like you know the bacteria in humans that allow organisms to live those molecules are governed by physical lost by the same laws that we talk about in chemistry and physics classes there's nothing special or unique about the molecules found in living organisms they are simply molecules that are governed again by physical laws so this persuaded this book persuaded a generation of to explore biology after World War Two this was an amazingly
influential book and this persuaded this generation that include great scientists like Francis "quotation mark cricket Jim Watson and many others to explore biology and to do this by applying concepts from physics and concepts from chemistry and on the results of our moral what I presented to you last week we talked a little bit about the structure of molecules so
this is good news for us the good news is everything you've been learning about in chemistry classes before now applies to biology there's nothing special about biology there's no sort of a life force that animates molecules found inside the cell now rather the same rules that you learned about in general chemistry that you learned in organic chemistry those applies to the molecules found inside yourself OK so let's talk a
little bit about those molecules found inside cells so
our goal is to understand 1st the reactivity of those molecules and then 2nd will talk about the non-covalent interactions so covalent interactions reacted reactivity 1st in organic chemistry you learn the powerful language of errors which are way of depicting the overlap of molecular orbitals let me I remind you of some conventions of those other areas in the conventions of this language of organic chemistry so the 1st of these is that these areas depict the overlap of molecular orbitals done so that they show for example electrons in a highest occupied molecular orbital overlapping with the the the unoccupied lowest energy molecular orbital of the reactor of the 2nd reactant of the reaction OK so in this basic reaction we haven't I mean we have a tone and the 2 of these are going to be reacting with each other so if you take a mean and you take each of any mix and together we can predict in advance the reaction will take place and here's why what we can predict is that alone here on the nitrogen is going to be highly reactive why is that what's special about that moment here it happens to be very high in energy it is our highest occupied molecular orbital and it's going to want to react with the the pipelines that the this Kerviel functionality of the Quito but so special about the Kerviel functionality of Quito's well it happens
to be a bit happens to have a on the low energy unoccupied molecular orbital hangouts breakdown
with these molecular orbitals actually look like what this looks like is the lone pair Of this nitrogen on this nitrogen is found in an orbital so it's in a high-energy status the highest of the occupied molecular orbital homo and it's going to be overlapping with the lowest energy on molecular orbital of the carbon all of the key town which happens to be the anti bonding orbital of the Thai baht OK this is what it looks like in terms of molecular orbitals and this is what it looks like on top in terms of organic chemistry and organic of organic chemistry good we organic chemists have agreed to the convention that we will depict complicated and reactions like this so 1 using the simplified on description can this is good
news I don't think anyone wants to spend lots of time on the test deriding what these like durables look like and trying to describe a deity bonding orbital in terms of the lobes and so-and-so for just way too complicated so we're going to be
using this description here now the real challenge for us comes from the fact that the more molecules that we talk about in biology on oftentimes have multiple functional groups it's not atypical for some of biomolecules have saved hundreds if not thousands of Kerviel's or to have thousands upon thousands of different lone pairs so the real challenge it is for us to figure out which of those long pairs and which of these car Kerviel's is actually going to engage in a reaction and when that happens for going to fall back on orbitals to decide which of these is going to be most reactive OK so again on what we're going to be talking about is this overlap of molecular bills that overlap of molecular orbitals the field unfilled overlap leads to the formation of new bonds and consequences breakage of others OK so when this lone pair overlaps with the affinity bonding orbital of the Lockerbie deal the piste orbital the result is a new covalent bond directed by this 1st era now on the other hand and we know that this comment can't have more than 5 bond Stuart Parkin had more than 4 months to it and certified bonds would be disallowed and so for this reason stock in concert with the formation of a new bond there's breakage of the Ottoman pie bond between carbon and oxygen of this Tito this is good
news right this totally makes sense because what we're doing is we're populating this bonding orbital and in doing so were making orbit were making that bond break right if you put electrons into empty bonding orbital What is a Due the bond rates hence the name and bonding the paper so
this overlap to be it's kind of like the peanut butter and jelly of organic chemistry were always going to be talking about a home homer highest occupied molecular orbital overlapping with the lowest unoccupied molecular orbital and in the same way that Peter butter and jelly tastes so good together of orbital overlap works so well it is so complimentary that in terms of reactivity OK so let's get back to a challenge against the challenge of is in biology we oftentimes have many different possible reactivity is we oftentimes have many different possible reaction mechanisms that we can draw despite that plethora possibilities while we will see it is that there is often times if only 1 true mechanism that dominant mechanism for a particular set of molecules and again this is good news OK so for example of me show you certainly easy case were going to be looking at reactions to possible mechanisms 1 that makes chemical sense and 1 that does not and so by doing this we can start to eliminate a lot of different examples OK so here is the clash of 2 possible wells in this reaction 1 possible mechanism as the lone pair attacking them getting bonding orbital the Carbondale and going through on the transition state that's depicted down here this reaction is an addition elimination reaction occurs through this transition state in addition and then in elimination reaction the chloride is eliminated giving us a substitution of nucleophile in place of chlorine can't make sense fundamental reaction a different type of reaction mechanism might look like this where the nucleophile directly displaces the chloride in doing so the the nuclear file lone-parent nucleophile is populating the Sigma star ANC bonding orbital of the bond between the carbon and according and so do possible mechanisms 1 involves the piste orbitals this 1 involves leasing star orbitals and on I guess at 1st blush these 2 reaction mechanisms might but look totally legitimate and both equally valid the problem is they are that we can actually readily eliminate the reaction mechanism on the right that that there is governed by the S into reaction instead what we can do is actually very quickly decided that only the addition elimination reaction will work so returning to this possible this clash of 2 wells when we look at a transition state our reaction corner diagram for the team possibilities which I think tells us which possibility is correct and which 1 is wrong OK so this transition this reaction cordoned diagram is depicted over here so In 1 reaction I showed him the previous slide the mechanism is an S & Q reaction and on the right this is the addition elimination reactions because so in this fight acknowledges the complicated diagram bear with me so over here these the starting materials this is the acid chloride This is the nuclear file and again but if this reacts through innocent you reaction you will get this left reaction corner and reactor in addition elimination reaction you get the right call cordon now but 2 possibilities a small little help big which is these to you is preferred Smallville Bighill radiologists imagine urine electron you have to decide which 1 would you prefer would you prefer ,comma tramping up the theory of you steeps the ski slope or would you prefer the much shorter OK I will tell you also that electrons are lazy that they are I do not extend any extra energy than they need and in doing so they're going to perfect preferred very strongly between little Heller or the much smaller Hill of the additional limitation reaction to the S to reaction this makes sense that's the way electrons live their wives so what this tells us is that yes there are 2 possible reaction mechanisms for this reaction yet only 1 is actually correct that only 1 that's correct is this 1 on the right the addition elimination reactions 1 on the left has to go through much higher energy S into reaction take now ,comma I'm going to explain in greater detail in a moment why it is that the 1 on the right is preferred than the 1 on the left 10 come to understand that I need to tell you about 3 possible components of orbital overlap so the energy
in this on interaction is proportional to 3 components take and when we go
back call Over here than reaction coordinate diagrams the king Y axis depicts energy were higher on the number of here indicates higher energy and again electrons being lazy prefer lower energy OK so that again is smaller hills preferred to the bigger help in terms of which side to go on the left side right side looking out this energy is proportional to 3 components component number 1 are charged charge interactions OK so if these molecules happened to have plus charges minus charges there and I know that will have some interactions and kilometer interaction but in addition it the the molecules have a repulsive interaction with each other that will also contribute energy as well OK so charge charge interactions but these are governed by the social convention like a opposites attract so and in social circles opposites attract I think is commonly accepted it works as a formula for dating websites and also works reasonably well as a formula for molecules as well so happily social conventions mirror of atomic formulas OK so charge interactions are 1 possibility if I go
back and you could see that we don't really have any charge interactions operatives in this mechanism as depicted here nucleophile as neutral as acquired also neutral charge interactions off the table
2nd term repulsive interactions so this would be if the the molecules have some sort of security hindrance that prevents them from overlapping with each other and and this is
a really important component in terms of preventing molecules from interacting it's used extensively in biology is used extensively in enzymatic catalysis once again over here that doesn't seem to be a possibility right nucleophile as a wide-open lone pair the acid chloride similarly wide open it has just the methyl group on the on this attached to it so there's really no repulsive interactions that operative here and by the way just remind you the repulsive term of this equation is the term that allows this camera to get counter
pounding in the nail in this wall a case so these repulsive interactions that's basically the and Pauly exclusion principle that means that electrons cannot occupy bit more than 2 electrons cannot cannot occupy the same molecular orbital OK and so for this reason the hammer starts coming on mail nail goes into the wall to get away from him OK they don't you something merge with each other and magically start to create some sort of hybrid material take things don't happen that way case a repulsive interactions clearly important not so operative
in this reaction right these 2 can snuggle up as close as they want there's no I mean you know prevention of that but I noticed your shrubbery last 1 attractive interactions this 3rd term I would describe as mysterious right this is not the terms that were used to talking about this attractive interaction is nothing more than the field unfilled overlap that I've been talking to you about today takes so here reduced down to its terms is a different and representation of the same equation 1 from up above in other words the reaction energy for particular on the set of interactions is proportional to cool onslaught which governs charge charge interactions on people lost their spirit terms minors the field unveiled over orbital overlap can exist the term over here that governs whether or not the molecules actually get to form and to break bonds the 2nd here's the deal the problem is that these 3 turns interact in a complicated way pay that if we go out and just you know start applying this equation every possible social situation we find ourselves and we're going to have trouble look at and I guess on the most obvious thing is you know the opposites attract rules only carries you so far said before you get married 2 years you know snugly significant someone it might be a good idea to find out whether that opposites attracting carries over to you know I don't know temperature the bedroom or something like that then so for this
reason that this this equation over here is a good deal more complicated when we take a look OK so opposites attract here's an example we have hydroxide we have nitrogen if they attract
so much negatively charged hydroxide positively charged hydrogen are 1st instead maybe you try to attempt to draw a bond and error between the living here on this hydroxide and the positive charge on the nite that would be wrong wrong and wrong will be totally wrong and the problem is that this is wrong at every level of the result here would be a bond to nitrogen and nitrogen being in the 1st row of the periodic table cannot possibly handle such a large number bonds remember the 1st row of the periodic table carbon nitrogen oxygen cannot handle more than 8 electrons around Manhattan payments for bonds 5 bonds totally wrong repair on another big problem with this that infuriates me is notice the on the bearer of starting on the negative charge and moving to the positive OK that's wrong too because I am again heiresses exposed depict overlap of and of orbitals I'm getting a little ahead of myself OK here's the correct way to do it the correct way to do this is to show hydroxide attacking the carbon and and displacing the possibly charge nitrogen in Essen to reaction case this opposites attract business only carries us so far peso that's our 1st problem I have is that this is that this really discharge charge interactions is very rare to provide an operative mechanism in organic chemistry and for that matter and bio organic chemistry really charge
charge interactions are very important for non covalent bonding not so important for covalent bonding a fact potentially very very misleading said cautionary note instead we need to turn to molecular orbital theory molecular
orbital theory can explain the otherwise unexplained and I'll give you 1 example of this before we go back to a canonical example that I showed you earlier cases for example of this methyl ester it has a preference for the scene confirmation versus the empty confirmation and onto a 1st approximation addition strike you as rather odd right because of and in this case over here the methyl group is as far as can be away from the lone pairs that populate oxygen those long pairs that stick up like Mickey Mouse years above the oxygen and so but this indeed confirmation should to a 1st approximation appeared to be the preferred orientation but you know
when we will look closely at this and we can using various spectroscopic techniques what we find is actually the
dominant confirmation is the scene confirmation and you can start to understand this if you think about the overlap of molecular orbitals the paper here is a you know here's again that's the same confirmation should appear to have some steer clash but again molecular orbitals explain why it is that it doesn't prefer that OK so I keep talking about what the orbitals I think it's time for us to dive right in and start to dissect them and look at them in greater detail and let's get started so In a town
in molecular orbital theory we're going to be talking about atomic orbitals so the Adams of the molecule each have they atomic orbital associated with it the of the nitrogen has some atomic orbital the oxygen the common even the hydrogen has some little tiny molecular about our some little tiny atomic orbitals associated with those of the atomic orbitals are grounded in S P E D E and F orbitals because that's where the electrons hang out they hang out shells or orbitals I prefer the word orbital which described as they orbit around the nucleus of the atom can remember those electrons that's the business end of battle that's what endows it with functionality that's what makes molecules the way they are OK now here's the thing but oftentimes these electrons are not simply in either as orbital or pure orbital instead they typically hybridized into hybrids of S P E but orbitals tape and farm used to this concept these hybrid atomic orbitals are given the names of the 3 sp 2 and sp here's the important part in case of this is reviewable I know that you've seen these hybrid atomic orbitals before this is the part that matters to us as chemical biologists and by a debtor chemist the best character Of these hybrid atomic orbitals determines its stability I hope we make sense OK so it s orbital is a severe we're in the very center this year is the nucleus of the out of nucleus possibly charged fees sphere defines the orbit of the electrons and in this sphere those electrons can cozy up as close as possible to the positively charged the nucleus case so this is an example great example of opposites attract an option attraction equal stability on the other hand up your orbital as picked it up here has the nucleus and no between the 2 loaves of the orbital space and nucleus is right here in the center again but that happens to be a zone of exclusion where the electrons are not allowed to exist around the electrons in this but are hanging around to either in this node appear his other down here they're not in our side Lou just load up here and borders of the Lobos appear there they're not allowed to get up to close To be positively charged nucleus and so for this reason the character of a hybrid electric of a hybrid atomic orbital determines distance ability Of that were bitter k of the electron spin and orbital conversely the key character defines the instability it defines how reactive and how nucleophilic those electrons in the hybrid atomic orbital really are OK that's kind of like you know you a defining how unhappy the electrons are guy happy electrons are found in the satirical s orbitals unhappy electrons are found in pure bills and what happens when electrons a are and unhappy situations Willie will move they will do everything they can to find more stable orbitals for themselves OK so these are the
atomic orbitals specifically the hybrid atomic orbitals but over here and I got the character of conveys confers reactivity basis any and so for example if we look at a series of of the alone hairs found on carbon what we find is that the the
higher the key character the more reactive that resulted lone pair will be the interest coming from ironically illustrated in terms of the system OK so here's an let alone here but in S P 3 hybridize orbital it's PK is 15 compare that against a lone pair in S on sp to hybridize the difference here is this truly dramatic OK so the PKK is only 40 in the case of S P 2 I realize oral and then it's way down at 24 down on in the hybridize orbital this is an enormous difference OK remember PKA are lot scale so in other words this guy up here is 10 to the 26 times more reactive than this guy down here and buy more reactive I mean how avidly it's commune leaching out in repeating hydrogen stripping protons off of its neighbors tells us almost immediately that for example by and you know so I or down metallic compounds that are going to be extremely added at grabbing protons to the point where the nearly the incredibly flammable and nearly explosive OK now this tend to the 26 times again is you that someone followed by 26 euros is such a large number it's hard actually 1st even imagine case so enormous differences this determined by this the character as character I
hope that I hope by now everyone is listening to us and every 1 of my class can explain why it is that these guys are so much more reactive than these guys and it should make sense just from geometric considerations as depicted here now these hybrid atomic orbitals recombined into but molecular orbitals in the molecules OK so the
hybrid atomic orbitals only carrier so far more often these hybrid atomic orbitals are shared between Adams and on that sharing is what gives us bonds pay now these molecular orbitals are given the names Sigma Pi and arm then OK so these hybrid atomic orbitals form bonds with other atoms and that yields on molecular orbitals the energy of these molecular orbitals 1 is defined very specifically and there's no way around us I basically just have to tell you I'd like you to memorize this chart on the slide take so please memorize the water of this reactivity where sigma molecular orbitals are lowest in energy pyre hiring energy and are even higher case of these the field of molecular orbitals these are molecular orbitals that have electrons in the Andes electrons are depicted by the up there as any down parents OK that's intervention that you've seen before OK now Sigma makes sense signal are the molecular orbitals that define single bonds best for single best for this defines a double bonds and so that's convenient right looks kind of like a double bond in the electrons in at orbitals are the lone pairs that hanging out around the adults OK so when the an orbital suppressant those are going to be the highest occupied molecular orbitals it's almost immediately back clues sense that we need to pay attention to those lone Paris and what about the unveiled molecular orbitals that we're going to counter a chemical biology found in 3 molecular orbitals and again I need to ask you to memorize the use of the order of the the energies take the lowest in energy a lot of people orbitals pure but also are exactly what I showed you a couple of slides again OK that's them these over here this is where P orbital looks like it has a loose and another load down here pure battles we find when we look at cover can I say take the but empty hole that is the cover cat and it is a pity orbital paid other electrons that surrounds the carbon that surround the carbon cover can and those other electrons are in S P 2 hybridized atomic orbitals so the remaining empty and atomic orbital up pure OK so most of the time we don't really have comic headlines the reason for this is that they are extremely reactive being so low in energy and so for this reason biology with very very rarely find cover cattle they we gave I'm going to show you an exception to this but for now let's keep in mind that we're just not going to see these very much and again the reason is biology takes place in water and carbon patterns react avidly with water prices start this is the intake bonding I'm compliment partner to the pie Bill and Sigma star is the antibody bonding on complement to the Sigma orbital and again on receipt of this relationship where on piste stars lower in energy than Sigma stock OK so here's what I need to tell you you don't have to worry about we're all those electrons are in a molecule and those really fabulousness appropriate to stop take a moment to to take a deep breath pause and appreciate that because the molecules we talk about when we talk about biology are fiendishly fiendishly complicated OK this goes back to the business they talked about earlier of the hundreds if not thousands of bonds the thousands upon thousands of of a lone pairs the good news is we get to simplify all of that complexity down to just worrying about the frontier of orbitals OK so in other words we only have to worry about the the frontier highest occupied molecular orbital and the frontier the West unoccupied molecular orbital decay in other words all you have to do is focus in on the highest occupied mode here our highest occupied molecular that has alone here in this and this and that the orbital war and also the lowest unoccupied molecular orbital over here so in other words if there's an available orbital it's can react 1st if there's a comic talent and everything else will come to a halt and cargo kind and gets a stake in the sun it gets to dance around OK if there is a lot here known Pierre will be the dominant reactivity then this is good
news because it simplifies everything we just have to look for the highest energy from homo and the lowest energy labor so what does this mean what this means is that this firefight applied and is the field frontier orbital and this is the orbital from whence all nuclear Felicity all basis city bomb springs forth the pen and I apologize for the kind of into antiquated English but really that's how we think about the this is the orbital that is the business end of this complicated molecule it doesn't matter how many possible known here as it has it doesn't matter and how many different possible configurations that has all that really matters is its highest and as low as low take again this is make
majorly important because it simplifies things for us so this homo highest occupied molecular orbital is field frontier all and it's a nucleophile in reactivity take now the intrinsic nucleophilic Felicity is governed by the energies of these molecular orbitals where again the highest in energy is this the end bonding the non-binding molecular orbital that has long hair and the lowest in energy there'd electrons of the signal or single bonds thanks to reduce it down to simplest terms what we're never going to be really saying reactions that start with Sigma Mont it just doesn't happen in the chemical biology of most of our reactions in spring forth organist spring from the lone pairs therein nonbinding orbitals occasionally electrons and pipe bombs but really we don't really have to worry about electrons a single bonds we know they're there you know they're there they're there but I what have to get wrapped up in them and this again is good news because there's a huge number of electrons in these complicated molecules that have you know thousands upon thousands about OK what about
the lowest energy unoccupied molecular orbital or the Louvre this is the unfilled frontier orbital and the lowest energy unoccupied is the most available from the molecular this is the molecular orbital that's going to be the center of attention for reactivity again and warrior these complex molecules this is kind of like that of the final to which all reactivity zooms toward OK again we need to know this water over here where P is lowering energy than pies Star which in turn is on energy and Sigma stock so if we're given the choice of different sites for nuclear file to attack nucleophile will choose every time to attack the keyword he is the slowest in energy and again the BCP orbitals we look occur because
if there are no cover Karan's present which again said earlier is exceptionally common because pot cover currents are very very rare in biology were Balaji takes place water so if there are new cover cannons president we can eliminate this 1 and we start focusing on piste orbitals
yet there are orbitals available for reaction there and it's likely that this will be the dominant the dominant reaction occasionally come across a molecule that doesn't have a lot of that doesn't have a price star in which case than you might have attack promising the stock this is a rare occasion especially as depicted here this is utterly wrong as depicted in the slide I find it offensive but I'm I'm stuck with it this might happen for example if there was a sulfur here and then you might have this sort of reaction taking place for now but let's keep in mind that we're going to probably be having reactions are lecture files the reactions are going to be a molecular orbitals consisting of NT bonding bonds cases it's the piste star antibody Pyotr but what orbit at I want to switch gears if you have any
questions about our molecular orbitals a hybrid atomic orbitals don't hesitate to shoot me an e-mail or on talk to the TA has come to my office hours etc. But we now have to talk I told you about what you do to decide what the reaction mechanism is we now have to talk about had actually tell me what that reaction mechanism that's OK so oftentimes a chemistry we have some notion of molecules are reacting but we need a clear way of communicating that reactivity so organic
chemists have developed this wonderful vocabulary by using errors and so let's take a closer look at what those heroes are the errors are going to be starting from highest energy occupied molecular orbitals the homeowners and they're going to be any day on the lowest energy unoccupied molecular orbital the headdresses a golden rule this is a rule that always applies failure arose started orbitals they and on orbitals they start on on homos state and on the matter and again there are always going to start on the highest homo and the lowest Molyneaux and on the lowest slimmer OK so again and that most there's the lowest energy occupied molecular orbital that's the most available and in turn that's the most direct reactive now the problem is again we oftentimes have many homeowners many little what's an organic chemist to with the students must so well endowed referred to this this idea of looking for the highest Hommel and the lowest loom but I can simplify and cut down to make it even easier for you miss it time to start put Japan on a lone pair and stop pushing electrons to end on the best electrified it's that easy if you're in doubt you're you're stuck there the at your desk during exam you don't know where to start but the pan on the long hair and just start drawing effect and the arrow on the best lecture file 9 times out of 10 99 times out of 100 maybe even more you get the answer right just by doing that OK so I need to talk to you about some rules we have rules because the civil language and in order for us to be clear in what it is that were communicating we need to have some conventions in the conventions referring to follow following this course are are the following and by the way before represent these conventions I should tell you I'm a stickler for these roles if you give me something that doesn't have that doesn't follow these 3 rules but chances are even if it's correct conceptually but it will get full credit take and the reason for this is is clearly turning in on a it assay the has incorrectly Rama too and your English classes something like that and what's your English professor going to do you know give you a date for a great ideas and and a for bad English know your professors probably gonna give USC overall because of the goal was to communicate effectively OK so in the same way when we speak using the language of areas we have to follow these conventions because this is what that convinces us that we know what we're talking about so the conventions are Aeros never indicate the motion of Adams and this is this is 1 of his
sons and another for the kind of profound but I think that all of us are used to having arrows showing you know I'm football player is over here to the quarterback who's back here then gets behind this guy and then another era shows this
diving forward those are the kind of heroes achievement drawing of you know I guess since you were more able to dry heroes cake which is to show emotion to share so the 4th dimension relate to show some element of time organic chemistry we don't use euros in that way rather were using heroes to depict overlap of orbitals were not depicting it in terms of time were depicting it in terms of thermodynamics not kinetics in other words were depicting an overlap of orbitals that's allowed OK so yeah I was not indicate the motion of adults we yes it's true that Adams must cozy up to each other and that's kind of understood that's working the background but that's not really what area showing arrows never start or end uncharged since these errors are depicting the interaction of fielded unveiled the molecular orbitals charges a relevant OK charged formal charge is 1 of those nice conventions that makes Lewis structures so much easier to understand yet the charge itself does not show you where the electrons are it doesn't show you anything about the molecular orbital and so drawing in era from 1 formal charge to another is worthless OK so again heroes never start or end on charge error instead furious on here is the 1 that really embodies everything there begin with lone pairs with pylons or single moms and and on unfilled orbitals can I want you to be really precise about how you draw these things that position indicates that you understand what is going on OK and on your arrows to precisely and where it is that that star orbital should be you're telling me something you're telling me a story you're telling me where it is that those electrons are going to appear and in doing that you're describing to me the reaction that's taking place OK so I need to have all of these things but of taking care of what it wanted to consigned to to Nunavut for exams and things like that that makes sense OK so but what we take a look at an example that so example but this is very simple problem face and arms the problem is that we might have a lone pair on the nitrogen over here I would like to do a a simple substituted nucleophilic attack was substituted nucleophilic reaction that substitutes for chlorine this lone-parent nitrogen .period this nitrogen Simeon everything looks good and this is a reaction very similar to the 1 I showed you at the very beginning that passed avoid the poisoned candied apple of simplicity rather fall back on homeowners and limits on show you what I need to do that I need to look at the screen is what I mean by avoiding that to be moved please in Apple of simplicity so In this example In this example there's a lone parent nitrogen it OK so here's a reaction again and the simple and I would call it even simple-minded possibility it is for the nitrogen to simply displays the chloride isn't a century reaction directed a simple case we have this reaction mechanism clear this case I recall an incident to reaction rates substituted nucleophilic 2 reaction and and this will give us and and this guy Over here the and then this can lose a proton it's all show space the base for example could be chloride but the OK now and this space candy protein and the this nitrogen giving us the product I want OK now what's wrong with this this is totally totally wrong and completely unacceptable it is also the it's upsetting to me what's so wrong about this and so appalling is and the fact that we're attacking a signal Astana orbital this is an attack on this Sigma star orbital over here right now we have
several perfectly good pie star but also available rates Sigma star it is not the lowest energy unoccupied molecular orbital far from at least 20 of pie star molecular orbitals that again the lower in energy when we explore those as a possible reaction mechanism OK so a
different mechanism would on starch soldier trust through here a different spin ends up more correct about mechanism Will this time hello yeah the lone pair in that and non-binding orbital of nitrogen attacking the star orbital of this Alpha Beta unsaturated carbon he'll let me show you 7 years lone pair it's now going to attack the pies .period molecular orbital electrons belts bounce all the way To the electorate negative oxygen OK so again this attack not on the Sigma star but attack on it the High star molecular orbital AT & T bonding orbital wobble why is this so much better this is better because the piste stars lowering energy then seeing and so for this reason we have In addition elimination reaction is greatly preferred OK this is actually the cooperative mechanism for this reaction OK ahead but you can continue on encourage you to do so in end you get this productivity there will be many times in this class all status that stuff up for you I'm going to that let you finish it off on your own and apologize for that this is a provision organic chemistry upper division chemical biology were at that point where I don't have to show you every step of their fundamental steps that I want you to know their fundamental steps that I expect you know but I'm not going to show them to you during every lecture that rather I want to go home I want you fill in on in your notes I will make sure that you know them because on exam I will ask you to show me the steps but on hand American blow on them today look I just don't have enough time to talk about them in classes of this place OK so the lesson from this is clear lesson is don't be tempted by simplicity and instead look at the overlap of orbitals which 1 is a better overlap the overlap with the Sigma Stora overlap with the piste off pie stock is lower in energy and it's there for greatly preferred OK let's move on but we've tried have to lower the it the no the other thing to make this work is that also have to make sure the major drawing a correct Lewis acid structure for the most part I don't think this is going to be a problem can 128 but it is important that you set things up correctly OK if you do are drawing for example by bonds to nitrogen a the reactivity of this an oxide is not going to be a parent because this is totally wrong OK similarly you know in terms of the number of all the bonds that you draw this helps you in terms of keeping track of things for that matter it's also essential for you to depict correctly the formal
charge 0 thanks sorry but this formal charge helps to guide us for example the negative charge on this carbon over here that should look kind of funny to you right cut down finds that she funny that should be extremely reactive so formal charge helps to guide us in terms of our of drawing these corrective mechanisms all have a lot more say about hydrogen bonds and really care about the 2 bonds we will see them in this class I don't miss out without going to today but I'll tell you more about hydrogen bonds in a moment OK so there
stocked with bonds for lone pairs and a Here are some correct depictions of errors OK so in this case were showing a on worldwide leaving are for an elimination reactions but the bromide takes off and noticed that the era so it's starting at the carbon bromine Bonn Canada words the electrons in carbon bromine bond decide to step out the door and leave with their friend the bromine giving us a bromide ion OK so here's electrons that a starting with another bond in this case applied by here they're starting with a signal on here their starting of the pipelines and here they are starting with the non-binding lone pair they all 3 of these cases are correct contrast that with these cases over here where I'm showing you by the heroes starting on charges this again is deeply appalling ,comma and totally wrong so there heroes do not start Adams self example like this so like that instead we want to draw them starting on the bonds themselves that should make sense right there is a trying to depict the overlap of orbitals and they need to start with the electrons are the electrons are found in these bonds electrons are not found in this negative charge they're not really found around this this and relied instead we're talking about the electrons that are shared between bromine and carbon those electrons that matter can now that's where they should start was talk about religion
and so areas need to end on Adams and bonds OK so here's alone here but not attacking a protons and it's in directly on the proton OK so here's a ending on and Adams the proton here is spending on the carbon of Aqaba Qatar and here it is ending on the hydrogen or the proton during an a or a B elimination stuff OK so Adams never terminate an empty space so for example 1 bromide is stepping out the door electrons don't simply hopped out and the door would open spent empty space for that matter this era would be wrong if it started that this carbon bromine and then had the electrons just going off and empty space that's not correct the electrons don't get to walk off and empty space that would be extremely well Hi in energy and extremely repellent rather the electrons get to end on this for me that I'm giving us bromide I think so heroes need to end 1 Adams they are they will depict again this overlap of some of fielded unfilled orbitals the
hydrogen for that matter is always attached to something have started to get down to my pet peeves but this is 1 of those pet peeves that does not pay hydrogen is not so bad that kind of like it is floating around next to the molecule rather hydrogen is directly attached to some particular Adam and this matters a great deal because we're it's attached will determine to a large extent whether or not it's going to be acting as an acidic
Proton perhaps not acidic at all OK so these terms Proton hydrogen hydride and hydrogen atoms are on 3 different depictions of the hydrogen atoms and the their 3 different meanings they're totally different meanings OK
so H classes the proton each minus the hydride each radicals hijacked but they really we don't find them just kind of floating around like this In the chemistry that takes place inside cells take protons
are just floating around inside the cell rather are always attached to something maybe attached to a water molecule to give you hide from you mind but the not just of hanging out there doing something OK hydrogen so but do not like being by themselves OK so in other words on which you want to avoid is showing proton just kind of hanging out in space waited around for some long hair electrons to attack that's not what happens Huygens doesn't get to do that OK and furthermore hydrogen radical also doesn't really occur nor does hydride I'm really occur there were rather in solution chemistry we find species affected either donate a proton donate a hydrogen radical or donate a high drive so what I propose to do His instead of depicting 8 plus as a reagent instead depict 8 plus as catalytic "quotation mark and "quotation mark each class those quote unquote we are going to tell us that yes we need age but what we need is we meet each plus that's been picked up and delivered by some other species in this case that might mean attached to this level this methanol molecule that's going to be delivery character where you can even write catalytic each day when in this case it's HA that's attached to and the conjugate base that's going to be delivering the protons take any 1 of those is
fine but it is important for you however to follow these conventions because they communicate to me but you know what molecular orbitals are being overlapped and it tells me whether or not to me you
understand the chemistry that's involved with these reactions OK 1 2nd OK I want to conclude today's lecture by discussing with you 1 other element of hydrogen atoms and that's the hydrogen bonds everyone needs a favorite Bond on my fear
bond is of course the great Sean Connery but today and when we talking to you about a 2nd favorite which is the hydrogen bonds OK the hydrogen government selected biology that it is essential for us to really get to understand it correctly OK so Hi give bonds are actually largely a cool on the interaction the described the sharing of a hydrogen atoms between 2 partners 1 partner is going to be our hydrogen-bond donor and a 2nd partner will be a hydrogen bond except the end of this hygiene bond will be detected by this dashed line pays to the staff line is are going to the convention Bryden bond rating uses a lot of pain hydrogen bonds for example hold together the 2 strands of DNA they on maker the molecular recognition possible the non-covalent interactions between molecules so hydrogen bombs and actually essential chemical biology however it turns out that the energy of the hydrogen bonds is very sensitive to the environment and the geometry that's involved with the sharing of that hydrogen the geometry in this case that I'm showing you over here it is a of a perfectly linear hydrogen bonds which is the other the best possible example OK so in this case the lone on water on this oxygen of water down here and is perfectly positioned to share this hydrogen bomb this hydrogen of this water appear and the oxygen hydrogen and oxygen are lined up as a straight line oftentimes that as in the case of Kosovo for example we can look at hydrogen bonds that are found in active sites of enzymes and we find instead of having this needs straight line we get and then the line instead that any line that then I mind much much weaker OK so this is kind of the optimal geometry optimal hegemonic sector which is a lone pair optimal hegemonic their donor and over here and this is kind this'll be our canonical hydrogen bonds now use 1 of the problems is 1 of the problems amongst others the is curved era curved errors and confound us when it comes time to talk about hydrogen bonds the reason is that curve eras and hydrogen bonds simply don't mix Kerberos depict the overlap of building on-field molecular orbitals whereas hygiene bonds are showing us and partnership of sorts between the donor and accepted and and out there really isn't the sort of overlap that means to covalent bond in the case of pension bonds and on this becomes tremendously confounding so for example but if you want to do show transfer Of the Proton of on this side nitrogen atoms to the lone pair of the oxygen you might be tempted to simply draw a hydrogen bonds in here and now would be utterly incorrect because this moment this hydrogen bond is basically saying the hydrogen is somewhere between here and there somewhere in the middle somewhere on the sides whereas over here in the case of the curly hair as you're saying now it's going pick this up it's going to pick up the proton wholesale hang on to it for a while and give you a positive charge oxygen this is the user to very different depictions so what we what we were
going to be doing in this class is showing those Steichen transfers as an explicit OK so hygiene bonds are going to be useful for us for talking about non-covalent interactions but not useful at all for talking about covalent interactions the reactivity that I have been talking to about
today it turns out that hydrogen bonds of the Proton transfers of the sort that I showed him the previous slide the sorts of proton transfers over here are extraordinarily fast OK they're oftentimes diffusion controlled in other words they hit the speed limit of reactivity for reactions that take place in solution and that kind of speed women and that kind of proton transfer ability is actually tremendously useful OK so this is a diffusion controlled reactions so Proton transfers to and from here Adams theory very fast on proton transfers for that matter in the same way that Huygens bonds require lineage untreated Proton transfers also were choir linear geometries and I can tell you that almost immediately this is going to annoy you this takes away 1 of the conventions that you miss learned back in software organic chemistry I know it was cool back then to show a proton transfer as a neighboring oxygen say picking up a proton over here the nitrogen and you have this completely ridiculous and totally crazy member during transition state issued calls me even say this but can you imagine for Adams getting together the former some sort of a very strange for Adam rain transition state it's totally and its total insanity even more insane noticed that the geometry between oxygen and hydrogen and nitrogen is not perfectly linear instead it's bent at a 90 degree an angle and me these kind of proton transfers do not happen this way instead they schools prefer a linear geometry so only linear geometries for going to count when we talk about Proton transfers and so for this reason I need to take this on this particular 1 step out of your vocabulary Khairallah was acceptable back and chemistry it's no longer acceptable I said so acids and bases are required to catalyze proton transfers and Thomas stations so instead of showing it like this on a much better alternative would not even alternative the correct way to depict this would be to show the oxygen picking up a proton drama and a cattle acid and then in turn the conjugate base of this acts as a base to deep-rooted neighboring nite positively charged nitrogen pneumonia miles OK so but in all cases we're going to see that acids and bases are required to catalyze the springtime transfers and that turns out to be a general rule and the good news for us said terms of chemical biology is that oftentimes are at all times we can find abundant numbers of different molecules that are all too willing to volunteer To those catalytic acids and bases and obvious examples would be for example what water can be Hydro EMI and act as a proton donor of water can also act as a base to accept protons and become a hydro knew my aunt and since all biology takes place in water and feel free to use water as their cattle lead-acid and their catalytic base OK so we've come quite a ways I've shown you Proton transfers I've shown you how to draw areas we've talked about the rules that govern the use of these of electron transfers in terms of field unveiled overlap of molecular orbitals but we're now going to transition to looking at some examples of this and I'm going to show you this on Thursday we talk about the molecules found on Earth that compose all living things so what we stop here we come back next time I'll be showing examples that applied the principles that we talked about today thank you very
Chemische Reaktion
Chemische Bindung
Hybridisierung <Chemie>
Elektron <Legierung>
Fülle <Speise>
Chemische Reaktion
Bukett <Wein>
Elektron <Legierung>
Aktives Zentrum
Neutralisation <Chemie>
Physikalische Chemie
Setzen <Verfahrenstechnik>
Gangart <Erzlagerstätte>
Sterische Hinderung
Matrix <Biologie>
Spezies <Chemie>
Lewisit <Giftgas>
Chemische Struktur
Gelée royale
Systemische Therapie <Pharmakologie>
Biologisches Lebensmittel
Aktivität <Konzentration>
Chemischer Reaktor
Eliminierungsreaktion <alpha->
Chemisches Element
Single electron transfer
Quelle <Hydrologie>
Biologisches Lebensmittel
Chemische Evolution
Spezies <Chemie>
Chemische Bindung
Chemische Biologie
Chemischer Prozess
Funktionelle Gruppe
Chemische Formel
Hope <Diamant>
Setzen <Verfahrenstechnik>
Sterische Hinderung
Organische Verbindungen
Radioaktiver Stoff
Heteroatomare Verbindungen
Monomolekulare Reaktion
Hybridisierung <Chemie>
Chemische Forschung
Chemische Forschung
Chemische Verbindungen
Freies Elektron
Einsames Elektronenpaar
Einsames Elektronenpaar
Potenz <Homöopathie>
Primärer Sektor
Chemische Struktur


Formale Metadaten

Titel Lecture 03. Reactivity and Arrow Pushing.
Alternativer Titel Lec 03. Introduction to Chemical Biology -- Reactivity and Arrow Pushing
Serientitel Chemistry 128: Introduction to Chemical Biology
Teil 03
Anzahl der Teile 18
Autor Weiss, Gregory Alan
Lizenz CC-Namensnennung - Weitergabe unter gleichen Bedingungen 3.0 Unported:
Sie dürfen das Werk bzw. den Inhalt zu jedem legalen und nicht-kommerziellen Zweck nutzen, verändern und in unveränderter oder veränderter Form vervielfältigen, verbreiten und öffentlich zugänglich machen, sofern Sie den Namen des Autors/Rechteinhabers in der von ihm festgelegten Weise nennen und das Werk bzw. diesen Inhalt auch in veränderter Form nur unter den Bedingungen dieser Lizenz weitergeben.
DOI 10.5446/18862
Herausgeber University of California Irvine (UCI)
Erscheinungsjahr 2013
Sprache Englisch

Inhaltliche Metadaten

Fachgebiet Chemie
Abstract UCI Chem 128 Introduction to Chemical Biology (Winter 2013) Instructor: Gregory Weiss, Ph.D. Description: Introduction to the basic principles of chemical biology: structures and reactivity; chemical mechanisms of enzyme catalysis; chemistry of signaling, biosynthesis, and metabolic pathways. Index of Topics: 0:07:01 What is Life? 0:09:07 Arrows Depict the Overlap of Molecular Orbitals 0:19:57 The Three Components of Orbital Overlap 0:24:27 Charge-Charge or Coulombic Effects 0:26:31 Molecular Orbital Theory Explains the Otherwise Unexplained 0:28:05 Combining Atomic Orbitals 0:39:56 Highest Occupied Molecular Orbital 0:41:57 Lowest Unoccupied Molecular Orbitals (LUMOs) 0:44:08 Anatomy of an Arrow 0:46:38 3 Rules for Mechanistic Arrow-Pushing 1:01:27 H is Always Attached to Something 1:04:48 Hydrogen Bonds 1:08:58 Proton Transfers

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