[ Silence ]
>> OK. Welcome back.
We're back.
So, hopefully everyone
got to see the lecture
on the YouTube channel
that I sent you.
It's been posted there.
That was Tuesday's lecture.
I'm a little concerned
if you haven't seen it
you might fall behind.
So, make sure that you
get up on it right away.
I'm going to try to
set up today's lecture.
So, it's not totally dependent
upon Tuesday because I have
to have checked out how many
views were on the last lecture
and so I know it can't
be possible be everyone
at this classroom.
So, I'm setting it
up today's lecture
so that it's not totally
dependent upon the material
presented on Tuesday.
But I do think the material
on Tuesday is foundational.
And so, future lectures
will refer back
to that material on Tuesday.
OK. Now, what is going on here?
OK. So, last time I was talking
about what causes reactivity.
And this is the property
by which molecules
that impinge upon each
other decide to form bonds
or break bonds due to that tight
interaction with each other.
And we're going to look
at some examples to that.
And our examples in the
beginning of the class are going
to focus on prebiotic synthesis.
So, this is synthesis
biologically relevant molecules,
the building blocks
of life really.
But using the chemicals
that might have been
found before any life
on the planet existed.
And I'll talk some more
about that in a moment.
And then we're going to switch
gears to a very important topic,
noncovalent interactions.
Noncovalent interactions
dominate all of biology.
And, well, I'm a huge fan
of arrow pushing and
covalent bonding.
The truth is, we
will get a complete
and accurate picture
of how biology works.
If we don't also
consider the possibility
that molecules can brush
up against each other
and then stay interacting with
each other and close proximity
by noncovalent interactions.
Not by forming any
bonds but actually
by forming hydrogen bonds,
by forming soft bridges,
by forming Van Der
Waals interactions,
dipole-dipole interactions,
et cetera.
So, we need to talk about
that because, really,
the next eight weeks or so
are going to invoke a lot
of noncovalent interactions, OK?
So, both of these concepts
are really foundational
for the rest of the class.
Tuesday, next week, well then,
be on to chapter three, RNA.
And we'll be doing two
lectures on chapter three.
So, if you have time this
weekend you might want to skim
through chapter three, take a
look at what's coming up next.
OK. Oh, and then
finally at the very end
on today's lecture I'll talk a
little bit about modular design
in biology because it
turns out that's one
of this concepts
that's very important.
And in middle, we started
to see a little bit of that
but we can look at it
in greater detail, OK?
I'm not sure exactly
why this isn't working.
OK. Good. OK.
So, some announcements,
I already told you
to read chapter two.
I told you about chapter two.
I'm changing this to every
odd and asterisk problem.
So, the answers to all the
asterisk problems are available
on the website for the textbook,
the answers to the odd
problems you can get
from Krithika [assumed spelling]
who will be here on Monday
and Miriam who will
also be here as well.
So, the TAs have the
answers to all the problems
that have been assigned.
And so, you can kind
of check your work, OK?
But I would like you to do all
of the assigned problems please.
OK. Let's see, there is one--
oh, and then chapter
two worksheet
of course posted to the web.
There is one handout this week.
And I'd like to take a moment
to go through that if we could.
So, bear with me.
I have to boot up my
browser and-- yeah.
So, the problem--
this worksheet focuses
on the journal article
assignment.
All right.
One moment.
OK. So, here I am on-- oops.
I guess I did it too quickly.
OK. So, this is from.--
let's see, where's my cursor?
It's maddening to try to find
where the cursor
is on two screens.
OK. So, it's on this screen
so it must be up here.
OK. So, here's the
obviously the Chem.
128 website and down
here, scrolling down,
journal article report 2013.
That's what I like
you to focus on.
OK. So, there are two-- there
are two sides to this handout.
The first side is an example
of what I'm looking for in--
a journal article report that
will receive an A grade, OK?
So, this assignment ask
you to write one page, OK,
no more than one page.
If it's more than one page,
I'll say it's not
following directions, OK?
So, just one page and the way
this assignment will work is you
will pick an article from
the current literature,
the current chemical
biology literature
and provide a one page
summary about that article.
The format of the
summary is as follows.
At the very top, I'd like you
to have a complete reference
for the journal article, OK,
the article that you've chosen
and note that this--
note the format up here.
That's the format that
I'd like you to use.
There are many different
formats.
I'd like you to use
this one, OK?
And just be consistent
throughout the class.
Then in the next
paragraph, they're going
to have a very short intro
that describes the broad
implications of the paper.
The last sentence
of any abstract
or intro should be the home run.
What it is that's important
about this paper and why it is
that people should care?
So, here it says, the results
provide important insight
into the nature of protein
DNA interactions taking place
in the cell.
That sounds pretty
important, OK?
There has to be some reason that
this paper, it would be useful
for other people to read, OK?
And that's that last sentence.
It's a key sentence
to any paper.
It's the last sentence
of the abstract
at the beginning of the paper.
OK. And then, I'd like you
to provide one paragraph
of background and then a
couple of paragraphs down here
with key experiments
and discussion, OK?
Some other-- Oh, and then notice
that there's lots
of figures in here.
It's OK to borrow these figures.
In other words, rip
them off the web.
That's fine.
Perfectly acceptable but credit
the sources for your figures,
OK, you could-- And I'll show
where to put the
credits in a moment, OK?
In addition, you know, put
your name up here, et cetera.
I'd like you to write
using active voice
and snappy engaging writing.
This is crucially important, in
fact, it's so important to you
and to me that I'm going to
reserve about somewhere between,
let's say 33 percent of
the points just based
on the writing alone, OK?
And here's why I think
this is so important.
When you graduate from
UC Irvine, you're going
to be expected to
communicate effectively.
That's a part of
having a college degree.
And in fact, people are going
to make snap judgments
based upon the effectiveness
of your ideas based on how
you communicate those ideas.
You might have the most
brilliant ideas on the planet.
But if you can't
communicate them effectively,
people will be unwilling
to listen to those ideas.
It is crucially important for
you to be able to communicate
in effective English, and
to grab people attention,
and to convince them that your
ideas are worth listening to.
And the first thing
that rankles, reviewers
or readers is a simple
basic mistakes, OK?
So, things like spelling errors,
things like grammatical
errors, OK?
If I see those, I will take off
substantial points regardless
of the brilliance of
the rest of the paper.
OK. It will drop you a letter
grade on this assignment,
if you have a single,
you know, major error--
major grammatical error, OK?
It's that important.
So, another way of saying
this is, in this day and age
where your computer tells you
if you have any spelling errors,
use that spell checker, use that
grammar checker and make sure
that everything is
totally perfect.
Furthermore, before you turn
in your assignment to me,
you should have revised
it many times.
OK. So, don't turn in something
and it's the first time
that it's been-- Don't turn in
the first draft, OK, really,
it should be about the 4th
or 5th draft before
it hits my desk, OK?
That's how important
this is, OK?
So, even small errors
are going to really hurt
on this assignment
and that's sort
of the way life works once
you graduate from UC Irvine.
You don't get a chance
to revise your, you know,
proposal to the NIH or
something like that.
Its it. You get one
shot at this, OK?
So, make sure that what hits my
desk has been revised may times
and I guarantee it to
you, if you revising,
it will be much better
quality that if you aren't.
And I'll tell you, this
is the way I write, OK?
So, when I'm writing
something, I revise it many,
many times before it
goes out the door.
I've notice that my papers,
the papers that my
laboratory publishes go
through 25 revisions before
they're ready to go out.
25 is on average, some
papers go through 30
to 40 revisions before
I send them out, OK?
So, that's like 30 or 40 drafts
of the same 15 pages,
10 or 15 pages.
And we'll just keep doing
it back and forth between me
and the co-author until we
decide that it's perfect,
because even tiny,
tiny little errors,
bias the reviewers against you.
It pre-- it force-- it makes
people pre-judge the quality
of the work even if that's
not an accurate assessment.
So, this really does matter a
lot for the rest of your career
and it matters a lot to me.
So, again, we're going
to be using active voice
and snappy engaging writing.
OK. Now, let me talk
to you a little
about the figures
and the experiments.
The papers you're going
to be reviewing are
from the primary
literature, meaning,
they're from the cutting edge
of chemical biology reports.
And in general in this
field that papers tend
to be rather meaty, OK?
It's not unusual to have
papers that have seven
or eight figures each
one with a ton of data.
You know, this is basically
the fire hose school on how
to impress somebody, OK?
So, it's not unusual for one of
these papers to have, you know,
a terabytes worth of
data in seven figures.
So, the challenge for you
is you only have, you know,
like half a page or so
to summarize that stuff.
So, what I would like you
to do is only include the
important experiments, OK?
Don't try to include
every experiment
in your one page write up, OK?
So, it's just one page and
this is just half a page or so
that you could dedicate
to the key experiments
in the discussion.
In this key experiments
and discussion you quickly
summarize the most important
experiments and then you discuss
what the implications are,
what was learned
from this studies?
OK? That-- what was learned
is crucially important, right?
This is really-- when you
read a paper, this is the kind
of nugget that you get back out
the reward for reading the paper
and that kind of
tells you, you know,
what it is that they
learned, OK?
And then at the very end, the
last sentence here is going
to summarize the key findings.
And again, this last sentence
is sort of highlighted.
And so, in that way
it gets more attention
than the rest of the work.
Thank you.
>> Welcome.
>> So, it becomes
crucially important
that last sentence reads in this
case thus this work demonstrates
how proteins traverse along
the negatively charged backbone
of DNA until finding a correct
sequence causing a remarkable
change in the structure,
the complex through a series
of hydrogen bonds and Van
Der Waals interactions
to the major group, OK?
So, some sentence like that,
they just summarizes everything.
Because I guarantee to you when
people read papers they look
at just a few things, OK?
I've studied how
people read papers
because that internal make you
a more effective communicator.
What they look for is they
look at the last sentences
of the paper itself, they
look at the last sentence
as a paragraphs like
this one up here
and then they look
at the figures.
OK. If you don't have a lot
of time to read something,
that's what you do, OK?
And this matter is a great deal.
So, I chair admissions
in chemistry.
I'm the chair of
Admissions Committee.
And we get like 500 applications
a year for applicants trying
to get a PhD in chemistry.
And I have to read all
those applications, OK?
So, what I do is I skim, and
when I skim, I start looking
at these last sentences
much more closely
than the inside in here.
I look at the first sentence,
first sentence looks
interesting.
I'll read the rest of paragraph,
first sentence looks
ordinary-- skip it.
And then maybe I'll
go on and take a look
at the last sentence just
to see what I missed
and the rest of it.
But that's the way
people read fast.
And the truth is, in
science where there's
like this fire hose of knowledge
that's pouring out at you.
And you can't possibly
drink it all.
We all read very quickly.
So, it's important that we cater
to that style of reading, OK?
So, again, focus on
this last sentence here
and this last sentence here.
I'll be looking at those
in really great detail.
OK. Now, on the second
page-- any questions so far?
And don't hesitate to
interrupt if you have questions.
OK. Now, on this second page I
have some directions down here
and then I have the references.
So, your references can
appear on the second page,
otherwise you simply
won't have room, OK?
And again, I'd like you
to use the same format,
the same style from
the references.
This is required, you must have
references and figure credits,
these are-- the figure credits
are where you got the figures,
where you borrow
those figures from.
And the references are what
you're referring to in terms
of your background
knowledge, OK?
So, what it is that
you use to tell you,
to help you understand
the paper, OK?
They appear here
under references.
OK. Couple of thoughts here.
Number one, I'd like you
to use references that are
from the peer-reviewed
literature.
So, the Wikipedia, does
not count as a reference
because it's not
peer-reviewed, OK?
And furthermore, 99.9 percent
of websites also don't count.
Your references must come
from peer-reviewed sources,
the one exemption that
I'll allow are textbooks.
So, if you want to have a
textbook as a reference,
I guess I'll accept that if
it's not too odd a textbook.
But for the most part, your
references should be coming
from what scholars would
consider good sources
and that means peer-reviewed.
If you have any questions
about whether
or not something is
peer-reviewed, see Miriam.
In general, the rule is,
if it's found in PubMed,
it's peer-reviewed, OK?
OK. So, these are required
and you can use Wikipedia
or websites for background
knowledge, you know,
to give you a quick heads up but
don't use them as references.
And if you're wondering
where it is you're going
to find good references, take
a look at the article's intro
and look at what the authors are
referencing, that a good start.
OK, assignment requirements and
I'm going to walkthrough this
so there's no questions later.
The first thing I'd like you to
do is choose a research article,
not a review article, OK?
So, review articles don't
report any new experiments,
review articles summarize
a bunch
of other experiments often times
done by another scientist, OK?
So, I write review
articles when I want
to learn something
new about the field.
OK. When I move into
a new area of science,
the first thing I do is
write a review article.
It's a great way to learn
the field, OK, but you know,
since I'm new to the field,
my sort of 10,000 foot view
is different than the view
from the trenches, OK?
So, for this reason and
also because I want you
to get comfortable at the
primary literature, I'd like you
to choose an article
that's reporting new
experimental results.
The way you'll know that you
have an article that's reporting
new experimental results and
that's not a review articles is
if there's an experimental
section.
Somewhere in the article,
there has to be something
about how the experiments
were done.
And if you have that
then you know
that you're not reading
a review article.
Again, if you have any questions
about whether it's a review
article or not a review article,
see Miriam or Krithika.
I have some directions
about the type of thought
that I'd like you to use.
You must pay attention to this.
This is important, number
three is, choose an article
on paper relevant to some
aspect to chemical biology
which again is using
chemical techniques to advance
in understanding of biology at
the level of atoms and bonds.
There's all kinds of
great articles out there.
There's a lot of science that's
taking place in astronomy,
in human physiology and in all
kinds of cool area a science
and I love reading
this stuff, OK?
At the end of the day, I go home
and I read science
and nature for fun.
OK. There's nothing
I like to do more
than to ready about that stuff.
But I'm teaching a classic
in chemical biology today
and so-- or this quarter.
And so, for you I'd like you
to be reading the chemical
biology literature, OK?
So, it has to be a chemical
biology paper and your choice
of article will tell me whether
or not you understand the
definition of chemical biology.
If you have any questions
about whether
or not it fits this
definition, see Miriam
or Krithika or myself.
The article must have been
published in these journals,
science, nature, PNAS,
chemistry, biology,
nature chemical biology,
ACS chemical biology
or cell during the
year 2012 to 2013.
This is essential, if
you turn an assignment
that doesn't conform to this
standards, I will hand it back
to you and tell you to redo
it minus a substantial point
for penalty.
OK. Now, the reason why I'm
doing this is two fault.
OK. Number one, by restricting
you to just these articles,
I'm ensuring that you're going
to be finding something that's
really important in the field
but other people in the
fields thought was note worthy
and exciting, OK?
It's really hard to get a paper
published in science, to do so,
it has to be something
really extraordinary, OK?
So, a pen bio paper that
appears in science chances are,
it was something that was
sort of earth shattering
to the scientist
in that field, OK?
So, you must choose it
from this journal articles
and then it must be published
in the year 2012 to 2013.
I do this 2012 to 2013
business to ensure that no one
out there is trying to use
last year's assignments, OK?
So, I'm one step ahead here.
And again, if it doesn't
conform to these requirements,
I'll just hand it back to
you and tell you to redo it.
OK. Now, this next one is
one of this, just tips.
If you're-- it's a good idea
for your journal article report
to relate to your
proposal, in other words,
if you're interested in doing a
proposal on DNA repair and how
to control DNA repair,
maybe amplify it
and accelerate DNA repair, maybe
that's your proposal topic.
Then choose a journal
article that relates directly
to journal article repair, OK?
That's always a good
idea, right?
Because now then you're
reading the current literature
in that area.
OK. Again, the book--
the journal article report
should be a single page
with figures, references
on the second page,
do not include any
other materials.
For example, do not attach the
paper to the journal article.
Again, conform to
the directions here.
This is the reminder that
is due February 14 at 11,
late policies strictly enforced.
OK. Now, the second part
is to receive credit
for the assignment, you also
must turn in in addition
to the hard copy
at 11 you must turn
in electronic copy
to turnitin.com.
And here's the course idea
and the password that you need
for that turnitin.com.
It's essential that you do that.
This will tell me
whether or not you were--
you should receive
points for turning
in assignment on time, OK?
And I think you know why
I'm doing this, we're talked
about plagiarism before.
It is a substantial problem
and you cannot succeed in life
if you do not have your own
ideas and your own thoughts.
So, I care about
your own thoughts,
not someone else's thoughts.
I want to hear your
own thoughts and so
for that reason I
will use turnitin.com.
It turns out actually
turnitin.com works pretty well
and every year, someone tries
to plagiarize this assignment.
And again, if this is the
year where I don't have that,
I will increase the grades for
everyone in the class, OK, like,
we will-- I think
I've said something
about right at the joint.
So, we will be moving
up the grades--
the total grade distribution
for the entire class
if I don't have a
single plagiarism thing
to deal with, OK?
For me this is a total win-win,
OK, because it's a real pain
in the neck for me to have
to write a letter to the dean
and then, you know, perhaps
even testify before an Adboard
to have someone thrown
out of school
for doing an academic
honesty in fraction.
I hate doing that,
drives me nuts,
but I will because I think this
academic integrity rules are
worth enforcing, OK?
So, if I don't have to waste
time on that, we all benefit.
OK, in addition on
the second page
down here I have an
academic honesty for him
which shows I think how
serious I am about this, OK?
So, the next page has something
that I'm asking you to sign,
reason why I'm having
you sign this,
is it turns out that one year,
someone's parents brought
in a high powered lawyer to
argue with me about this.
So, it turns out you can't do
that because I'm going to insist
that you sign this in order
to have your report graded.
All right.
Now, grading, I know,
isn't this incredible?
Well, I've teaching
for 12 years.
I found every possible
crazy scenario.
So, this is why pedantic that
I'm going through all these.
OK. Let me tell how I
am going to grade this,
from actual little points,
use correct English grammar,
spelling and diction.
OK. So, choose the correct
words, spell correctly,
and if you have any
trouble with this,
if you know that your English
isn't so great, don't panic, OK,
we have resources on campus.
There's a campus writing
coordinator who can help you,
there's an office across campus
where people can read your work
and then give you feedback and
correct things about that work.
You need to tap in to that
resource right away, OK?
So, I'm talking to you about
this a month in advance.
And so, you have plenty of
time to tap into that resource.
It's really important
that you do.
So, if your writing is not
your thing, don't panic,
you have a month to
get the assignment done
and its only one page but you're
going to make it a perfect page.
OK. The next part, strive for
simple clear sentence structure.
I'm really a strong believer
that you should write
like a journalist, you know,
like writing for a newspaper,
an actual newspaper like
New York Times not like,
you know, some other stuff.
But if you have simple
sentences,
people can better
understand you.
Now, I know, I am the worst--
I routinely make this
mistake all the time.
So, I have to consciously,
when I'm writing, force myself
to simplify my sentences and I
realize at that last sentence
that I read to you
earlier today was kind
of a mess, it was way too long.
And so, a sentence like
that I might divide
up into two sentences now.
So, a good rule of thumb is
if your sentence goes for more
that two lines, it's too long.
Start cutting it up
into a shorter sentence,
shorter sentences are
just easier to understand
and the goal here is for
you to communicate clearly
and to impress people with
the power of your ideas,
not snow them with just
complex concepts, OK?
Your idea-- the goal here is
to be simple, direct and clear
and powerful in ideas, less
powerful in just, you know,
over intellectual,
you know, complexity.
OK. Next thing, summarize
the article careful--
correctly, I read
those journals,
I will probably have
read the journal article
that you're proposing
as you report before,
as well of Miriam and Krithika.
So, if you're wrong,
you're wrong
and I'm going to call you on it.
Include useful figures,
I know it doesn't seem
like that should
ever happen, right?
But it actually does happen.
If you have questions about the
journal article, see Krithika,
see Miriam, see myself.
We could try help you
interpret what's going on.
Carefully, follow directions
regarding the format that's
provided here.
And then again,
do not plagiarize even
short phrases, OK?
Now, hopefully I haven'
scared you too much
about the plagiarism,
every year people complain
that I'm scaring them too
much about plagiarism,
but I wouldn't have to do this
if I didn't have this
problem every year, OK?
So, let's make this
the wonderful year
where I don't have this problem.
All right.
Any questions?
All right.
Yes, I hopefully covered
every possible outcome--
oh great, a question over
here, what is your name?
>> Ashley.
>> Ashley.
[ Inaudible Remark ]
OK. So, yes, you could
quotes but put them in quotes
and then put a reference to show
where you got the quote, OK?
But yes of course, that's
perfectly acceptable.
I think that's actually
a good way
to do things, OK,
other questions?
Yes? And what is your name?
Suzy.
[ Inaudible Remark ]
Absolutely.
OK. Thanks for asking.
So, Suzy's question is, you told
us not to use a review article
as the thing that you're going
to be doing the report on,
but you can certainly review
article, use review articles
as background material
and references, OK?
In fact, that's an excellent
use of review articles.
So, review articles
are great way,
they're like textbooks basically
of the current studies,
you know, the most recent stuff.
OK. All right.
Good luck on this assignment,
I can't wait to read them,
it turns out it's a really
fun assignment for me to read,
it's like-- the annual report
of what's happening chemical
biology over the last year.
I might make the very
best of this available
on the course website.
I've done that several
years and the truth is,
the really good ones like
the top, say 20 percent
or something, are really great.
They're actually terrific
summaries of cool papers
in chemical biology, anyway,
I look forward to that.
OK. That's it on announcements.
I know. We spent a long
time on announcements,
but it was worth it because we
covered a lot of the material.
OK. Let me summarize
where we were on Tuesday,
at the end of the
Tuesday's lecture
and then we'll jump right
in to today's lecture.
On Tuesday, I taught you
a really powerful equation
that pretty much
governance every interaction
between molecules, OK?
This is the simple stuff like
your fingers touching your desk.
This is the complicated stuff
like digesting the glucose
that you've had with your
coco puffs this morning, OK?
So, this one equation
governs all of those types
of interactions between
molecules.
What it showed us is
that the energy required
for energy involved in that
interaction is proportional
to the sum of the
filled-filled overlap.
OK. So, this is where
the molecules decide
that they're not going
to form a bond with each
and instead they're going
to repel each other.
OK. So, this is your finger
touching the desk, right?
The electrons on the tips of
your fingers are interacting
with the electrons on the
tip of the wood desk, OK,
and is preventing your fingers
from going plunging right
through that wood desk, despite
that fact that there's a lot
of air and there's a lot of
vacuum in there are well,
a lot of space that's not
covered by those electrons.
Despite that though, the Pauli
Exclusion Principle teaches us
that electrons cannot overlap
with other electrons and so
for this reason,
this filled-filled overlap
dominates repulsion.
In addition, there's
a term for Coulombic
or charge-charge interactions
and then there's a term
for a filled-unfilled overlap,
and last time I spend a lot
of time talking about this
filled-unfilled overlap,
this is a minus term
in the above equation,
it turns out this
is a minus number.
Basically, that's the term
if the molecules decide they're
going to react with each other.
That glucose, the sugar
that you ate this morning
for breakfast decides to
interact with, you know,
an enzyme in your stomach
and starts getting digested.
So, in that case, what'
happening is there's orbitals
that have filled that
have electrons in them
that are finding a lower
unoccupied electro orbital
to interact with.
OK. And we also discussed how
arrows depict this overlap
of the lowest LUMO and
the highest HOMO, OK?
So, in this case, these arrows
are showing us how the electrons
are flowing between a high
occupied molecular orbital,
electrons in a high
occupied molecular orbital
down to a lower energy, lower--
lowest unoccupied
molecular orbital.
And then, that's the essence
of forming a covalent bond.
When that happens, that's
when you get bonding, OK?
We also talked about
some very specific rules
for arrow pushing.
Arrows begin on electrons
and end on empty orbitals.
That's it.
They are not ending in space,
they're not ending on charge,
they're going to be
ending directly where it is
that molecular orbital
that unfilled molecular
orbital should be.
So, if it's a pi-star orbital
you should try the arrow that's
going to end approximately
where the pi-star
orbital actually exist.
OK. This is a language
that we use to communicate
with each other, to tell each
other how this bonding actually
happens, OK, without this
language and some rules
to this language, some
diction, some grammar, you know,
we won't be as communicating
as effectively.
OK. Any questions about
Tuesday's lecture, OK,
or what we saw on Tuesday?
I'm going to be showing
you specific examples,
yes, question over here.
[ Inaudible Remark ]
Yeah, and what is you name?
>> Sergio [assumed spelling].
>> Sergio.
[ Inaudible Remark ]
OK, fair enough, why
don't I start there?
OK. Other questions for Tuesday?
All right.
So, on Tuesday, just give
me one sec to pull this up.
I showed you the slide that
described hydrogen bonding,
and let me just see if could
find this thing, yeah, OK?
So, in this case, this is a
depiction of hydrogen bond,
notice that they are--
is a donor, this NH,
and there's an acceptor,
there's oxygen,
the lone pair on this oxygen.
And the problem is that this
depiction of hydrogen bonds
which [inaudible] we are going
to use massively complicates
our attempts to draw arrows, OK?
Sp, while it is true
that the hydrogen
in this hydrogen bond is hanging
out with oxygen and also hanging
of the nitrogen, it makes
it very complicated for us
to draw arrows involving
these hydrogen bonds.
So, instead of drawing
hydrogen bonds like this
in reaction diagrams where
we're doing arrow pushing,
instead what I like us to do is
actually show the hydrogen fully
donated over to the
oxygen over here, OK?
So, fully donated
to the acceptor, OK?
So, here's the lone pair on
oxygen, picking up this proton,
and then electrons,
bouncing to the nitrogen, OK?
Sergio, does that make sense?
OK. Great.
All right.
I want to pick up where
we left of last time.
And again, we'll be looking at
a couple for examples of this--
OK, here's where I left of.
The molecules of life
on our planet are actually
pretty simple molecules, OK?
And we've actually seen
them structurally before.
So, this is the chemical
structure DNA, I'll be leaving
out stereo centers
but it definitely provide
kind of a quick overview.
And the question I want
to start with today-- OK.
So, here's what they're
made out,
here is two questions I
want to start with today.
First, what composes
these molecules?
OK, where did this DNA
stuff originate from?
What is it made out of?
And then, where did these
pieces, these building blocks,
here the pieces over here, where
did those pieces come from?
OK. So, that's-- those are
the questions that are going
to challenge us today and we're
going to be talking about this
in the context of
pre-biotic chemistry.
So, this is chemistry that we
hypothesize might have taken
place before life
on the planet arose.
OK. And we have some ideas about
what the planet's chemistry look
like by looking at the
record, the geological record,
and also by studying other
celestial bodies, OK,
other moons and planets.
So, for example, when
we look up at the moon--
a moon of Saturn
called Titan which looks
like this we can see
building block molecules,
chemicals that are present
at high concentration.
And we could see this
using spectroscopy.
OK. So, the same UV absorbents
techniques that you learned
about back in general chemistry
they're applicable here, OK?
So, we see, you know,
characteristics stretching
of a carbon nitrogen triple
bond that tells us definitively
that HCM must be present
on this moon of Titan.
OK. So, based upon that
example and note example,
and also looking at
geological record on our planet,
we hypothesize that our planet
and its very early days must've
had those chemicals available.
And if those chemicals
were available,
they can compose
the building blocks
that are shown here
on the left, OK?
These pieces over here
from these pieces we can then
build much more complicated
things like just adenosine
building block of--
in this case, RNA but
also DNA as well, OK?
So, the key though is that there
has to be some energy source
and one very effective energy
source is Ultra Violet light
which will be invoking
today, OK?
OK. So, here's the
picture in the book,
same as what I've
showed you earlier.
So, again, here's
adenosine down here.
Adenosine is composed of
a ribose and an adenine.
And you can actually
derive this adenine directly
from just a bunch
of hydrogen cyanides
that react with each other.
OK. So, if they react with
each other in the presence
of UV light, you basically
put these things in UV light,
shine the light on it and then,
you know, wait a little while,
you will get out-- a low
but significant yield
of adenine, the base.
And you could also get out
ribose if you have a bunch
of formaldehydes that
are bubbling around, OK?
So, formaldehydes
over in this reaction,
adenines in this reaction, if
you-- dehydration reaction,
you will then get
adenosine which is one
of the building blocks
for RNA, OK?
And so, on today is an
example of arrow pushing,
we're going to show exactly
what's going on there, OK?
OK. Before I do, I need to
talk to you a little bit
about hydrogen cyanide
also called prussic acid.
This is a very weak acid
and it has some rather
unique properties.
So, hello, it's called an acid.
It's PK of nine, hardly
qualifies it to be an acid,
right, PK of nine is not what
we call a really great acid, OK?
But nonetheless, it has the
ability to donate protons
and I want to remind you of a
rule which is the PKA is equal
to the pH where half
is protonated.
OK. So, in other words, this
PKA of nine tells us that the pH
of nine, 50 percent of the
hydrogen cyanide will be HCN
and then 50 percent
will be cyanide.
OK. This is one of those things
that I'm hoping everyone knows
and if you don't know,
go back and review it
from your general
chemistry book.
Here it is, pH nine, you
have a one to one ratio
of hydrogen cyanide
to cyanide, OK?
And then, each pH unit is a
factor of 10 on this ratio.
So, as the pH drops, you get
more HCN down to pH seven
if neutral, we have a 100
folds more hydrogen cyanide
than actual cyanide, OK?
Turns out that hydrogen cyanide
is actually very, very reactive.
And so, the first thing I'm
going to be showing you is
who hydrogen cyanide can be used
to form a molecule we
effectually called DAMN,
diamino maleonitrile, OK?
So, that is our first
challenge is at a pH of nine
where you have a 50-50 ratio
of cyanide to hydrogen cyanide.
We can actually mix these
things together get the pH right
and then extract out of it this
diamino maleonitrile or DAMN
and let's start there, OK?
OK. Before I do any questions
that what we've seen so far?
OK. Always makes me nervous
when there's no questions.
[ Noise ]
OK. OK. So, the pH of
nine, we have a 50/50 ratio
of cyanide to hydrogen cyanide.
These two have-- I would
say opposite reactivity
to each other.
Where the cyanide is a
terrific nucleophile,
the hydrogen cyanide is
a terrific electrophile.
So, it's very interesting.
Say molecule, behaving in
two different ways depending
on its protonation state.
OK. So, very first step here.
[ Noise ]
This will give us--
oops, oops, oops.
Sorry.
[ Noise ]
One moment.
One thing I've learned--
[ Noise ]
OK. So, this is the incoming
cyanide having attacked HCN.
And we could do a bunch, a
proton exchange reactions
which I'm going to
show you at first
and eventually I will leave out
but I will expect
you to know them.
Here is the first one of this.
This is the nitrogen picking up
a proton from HA that's nearby.
What is the identity of A?
It's probably cyanide.
Its exact identity?
Not so important to us.
OK. All the reactions
I'm talking to you
about over the next-- actually,
for the entire quarter are going
to take place in water.
There's plenty of other
sources of protons available,
these are complex mixtures.
So, I encourage you to
use this HA nomenclature
which I will except on
exams and quizzes, OK?
OK. So, we pick up a
proton in this first step.
OK. A word about these
equilibrium arrows,
for steps that-- for
many of the steps,
I'm going to be using
these backwards, forwards,
arrows indicating that an
equilibration is taking place.
Honestly, at your point I'm not
so concerned about that, OK?
In other words, just
put some arrows there.
It's nice to show that
you can have protonation
and the deprotonation and this
could go backwards and forwards
but it's not my primary concern
for a class at this level, OK?
So, and don't get worked
up about the arrows
is what I'm trying
to tell you, these arrows here.
Get worked up about
the orange arrows
that are showing
the reaction, OK?
Another proton transfer.
[ Noise ]
OK. Notice that I'm
adding in the formal charge
and the formal charge is useful
because it helps us
keep track of electrons.
Furthermore, notice that
each of my arrows is starting
on a lone pair and
ending directly
on where approximately the
antibonding orbital should be.
There will be a sigma star
orbital that is in line
with the bond between
H and A over here.
And so, this arrow ends directly
where that sigma star
orbital should be.
Arrows again show overlap of
orbitals, and it is important
that our arrows depict that
overlap of orbitals accurately.
OK. So, that brings
us to our next step.
We now have a protonated
nitrogen.
It's actually iminium ion,
iminium is an exceptionally
good electrophile.
You could think of
it as the equivalent
of a protonated carbonyl
that is nitrogen analog
to this carbonyl, OK?
So, this is a very effective
electrophile eager to pick up--
this cyanide for this step to
happen and that neatly sets us
up to have this guy here.
[ Noise ]
Sorry. OK.
So, this guy here, NH2,
there's the lone pair
from the second arrow.
[ Noise ]
OK. That sets us up nicely
and then we can do exactly
the same step, yet again, OK?
So, exact same step this time
on this cyanide over here.
[ Noise ]
OK. By the way, this
sequence of arrows is
of course covered in the book.
I'm showing you because we
can discuss it all on a bit.
I won't show you all
of the reactions
depicted on the book, OK?
This is kind of early
days for us.
We're starting off slow.
But, later I should tell
you about reactions that--
where the mechanism is depicted
in the book and I'll ask you
to go and learn that mechanism.
But for now, I'm just kind
of starting off things
at a nice comfortable pace, OK?
So, this sets us up with
the following product.
OK. So, here is one
triple bond, NH2, carbon.
[ Noise ]
Here. OK. This guy over here.
And this is starting
to look very much
like diamino maleonitrile.
We have two cyanides-- by the
way, I better put the structure
of this just-- by the way, this
is what we're trying to make.
It's always good to keep in mind
what the structure of the target
of your mechanisms is, OK?
So, this is our target.
OK. Tempted to put an arrow
after that or exclamation point
but I held myself back.
In any case, yet another
proton transfer step.
OK. This become very
routine after a while,
they should be almost
second nature.
And I'm mostly going to a bond
rotation step as well, OK?
So, rotating around this
carbon-carbon single bond should
be very tussle at this point.
[ Noise ]
OK. So, we're here and
next step is a crucial one.
OK. So, remember earlier, I
told you that-- oops, oops--
by the way, if you guys spot
errors, please correct them,
errors, please correct them.
It's very easy for me to make
errors 'cause I'm standing
up before this board
and have a lot of,
you know, people looking in.
So, often times I make
errors, please do not hesitate
to interrupt me and correct, OK?
I don't mind at all.
OK. That gets us to
another iminium ion.
[ Noise ]
OK. Again, this iminium
ion you could think
of as being the equivalent
of a protonated carbonyl,
it's the aza or nitrogen analog
to a protonated carbonyl,
terrifically reactive, that
sets us up to have a minus,
this is the conjugate
base of the HA
that I've been invoking
all this time
to do this last deprotonation,
OK?
So, that sets us up for forming
this guy and I'll just redraw it
over here so it looks just
like it does over there.
[ Noise ]
OK. So, diamino maleonitrile,
OK, make sense?
Pretty straight forward
reaction, right?
And what's so extraordinary
about this?
As we've see the
condensation of three cyanides,
three hydrogen cyanides
have come together
to give us a building
block-- oh, sorry--
make that four hydrogen
cyanides or two cyanides
or two hydrogen cyanides.
In any case, we built up a four
carbon building block using
nothing but one carbon
fragments, OK?
So, in a very straight
forward sequence, OK,
pretty amazing, all right.
Why don't we take a look next
at the next step
here to form adenine.
And then, we'll move
on from there, OK?
Any more questions about this?
Again, this is very-- this
is identical to the book,
this is basically figure 220.
And so, I'm going
to go on from here.
OK. Now, the next
step involves-- OK.
All right.
OK. So, we've seen formation
of this diamino maleonitrile.
I'm skipping a couple of slides
here that seem redundant.
What's going on?
All right.
OK. There is a UV
catalyzed step over here
where this diamino maleonitrile
is then converted using
another-- we just
say it, no, sorry,
using the molecules
depicted here,
there's a UV catalyzed step
from which you can convert
this DAMN to AICN, OK?
And actually that step is
a little bit more involved.
I've had students over the years
figured it out for themselves
and you could certainly do that,
it's not that crazy involved.
But it's involved enough that
I'm going to leave it out, OK?
So, this step here, don't worry
about, it involves UV light
but this gives us a
key building block
from which you can make
either adenine if you add
in HCN another hydrogen
cyanide or you can make guanine
if you add in urea, OK?
Two molecules again that
we suspect were available
on prebiotic conditions, OK?
So, in one step you can
go either here or here.
And question over there?
Yeah.
[ Inaudible Remark ]
OK. That's a good question.
There is a-- so, in
short, the answer is no.
Likely, both come from-- both
E and Z, the molecules, well,
that sounds funny,
are being formed, OK?
The ratio is, however, probably
not perfectly 50/50 do likely
to dipole effects, OK?
So, when molecules form, they'll
try to minimize having a dipole.
A dipole is a higher
energy state.
And you can imagine these
nitriles pulling electrons
in one direction.
In this case, both dipoles will
be pointing off to the left, OK?
Interesting question but don't
get too worked up about it, OK?
Other questions?
All right.
So, this gives us two
key building blocks,
two bases of DNA quite
straightforwardly.
And I'm gong to not show you
these two steps here, OK?
But, I suspect that
all of you can do them
and we have a worksheet
problem like that, OK?
Good. OK. So, we don't have to
necessarily go through it today.
All right.
In addition-- so these
types of molecules
that have two rings
are called pyrimidines.
We'll talk more about that
when we get to the DNA bases--
oh, you know, I'm realizing
next week is DNA not RNA, OK?
So, next week, we'll
be talking about DNA.
And we'll talk about more
about what this definition
of pyrimidine means.
Now, in terms of--
did I call this--
these are purines, OK, purines.
The pyrimidines have one
ring like these two guys.
OK. So, cytosine and uracil
are examples of pyrimidines.
And you could form
the pyrimidines
in a quite straight forward
manner using these simple
building blocks over here, OK?
And, this is-- I have-- this
is figure 223 in the text
that actually gives you
exactly the mechanism
and because I said the text,
I'd like you to just go
and learn it for yourself, OK?
I'm not going to spend
time actually doing
to the arrows today, OK?
But, it's a very straight
forward sequence, OK?
OK. In addition, so, OK?
So, from this, we can
form all the purines,
we can form all the pyrimidines
using these reactions
that involve hydrogen cyanide.
And on occasion,
this cyanoacetylene,
this is cyanoacetylene over here
but from there we can basically
derive all kinds of things.
In addition, in order to make
DNA or RNA we also need some way
of making ribose, OK, in the
case of RNA or deoxyribose
in the case of DNA, turns
out that you can actually make
ribose rings quite readily,
they are thermodynamically
very stable using a series
of formose reactions that form
these ribofuranose structure,
OK?
And this uses something
called the formose reaction.
Formose reaction
consists of aldol
and then two benzoin
reactions, OK?
So, we need to know
two reactions
to understand this
formose reaction,
the aldol which hopefully,
you know.
And then also the
benzoin reaction
which will be unfamiliar to
you and I'll go through it.
OK, every one still
with me so far?
Let's take a look first
at this benzoin reaction.
The benzoin reaction is one
that stitches together two
aldehydes using sodium cyanide
as a key reactive
intermediate, OK?
It's going to the cyanide, it's
going to form a key intermediate
and make possible this--
otherwise, kind of
unusual aldol reaction.
OK, every one still with me?
OK, good, why don't
we take a look first
at the benzoin reaction?
And then we'll take a look
at the formose reaction
for aldol, OK?
So, to recap, what I've shown
you is you can make the DNA
bases using the reactions
that are depicted here.
You can line them up
in different ways.
Now, I'm going to be showing
you how to make the ribose rings
that are also an integral
part of a DNA and RNA.
OK. So, let's get started first
with the benzoin reaction.
OK. The name isn't how you
solve, but I actually are
as so important, but I
actually find the names
of reactions you solve to
kind of organize in my head,
you know, a large
amount of material, OK?
So, in this reaction we're going
to start with formaldehydes.
And in the presence
of cyanide use this
to make this guy here, OK?
Just to make sure, we're
doing this right, yes.
OK. So, cyanide we've
seen an act
as a nucleophile
before right, OK?
Formaldehydes, terrific
electrophile, you can't go wrong
if you start lining up
the electrophiles together
with the nucleophiles, OK?
So, here we go.
So, here's cyanide, OK?
So, cyanide can attack
here, giving us-- oh boy.
All right.
[ Noise ]
OK.
[ Noise ]
So, cyanide attacks there
and that gives us an
alkoxide and a cyanide.
Now, amongst its many
properties they make cyanides
such a terrific intermedian
terrific reagent
as it is extremely
electron withdrawing.
So, that makes protons
that are alpha
to the cyanide very susceptible
to deprotonation, OK?
So, here is that
deprotonation, OK?
Now, the result into
electrons can be in residents
that will actually be
stabilized by virtue
of being adjacent
to this cyanide, OK?
So, I'm showing you
this is as a--
I'm showing you this
intermediate-- wait, wait, wait,
did I lose a iodide
carbonate, sorry.
[ Noise ]
OK. So, I'm showing you
this as a carbon ion
but really what's going on
here is a more corporate way
to describe this would be
as a resident structure
with the electrons bouncing
to the electro negative
nitrogen, OK?
I'm also a little
uncomfortable of the idea
that you have two negative
charges on the same molecule
and the pedantic part of
me would actually insists
that we redraw it but I
don't have time today.
So, I know that what was
working me into corner.
I'm going to get some
crazy thing on our midterm
and be forced to accept
it but-- so be it.
OK. Second molecule formaldehyde
can then be attacked
by this carbon ion.
Note that I'm drawing this arrow
in this rather convoluted
S configuration.
I'm doing that on
purpose because I want
to have the arrow attacking
the pi-star antibonding orbital
of the carbonyl.
If I don't draw the arrow going
zooming down here then zooming
up here, it's not going to land
on that pi-star antibonding
orbital.
And I think that's
important because again,
that's how I communicate
effectively
that I know what's going on.
[ Noise ]
OK. Last step here, picking
back out the cyanide.
And so, that gives us the
product gets us one step
from the product, product
then picks up another proton.
[ Noise ]
OK. And then this
is to the product.
OK. Now, here's the thing,
if we can form aldehydes--
like this one then we're in
good shape to actually be able
to start doing aldol
reactions to build
up to carbohydrates
likes ribose, OK?
So, this benzoin
reaction neatly sets us
up to actually start
building riboses, OK?
And again, the riboses are these
building blocks of life, OK?
Notice how close we are, right?
We have two carbons,
we have two oxygens.
This is starting to look very
much like a carbohydrate, right?
Where carbohydrates are
these hydrates of carbon
that have an equal number
of water molecules are--
an empirical formula
it has water
in addition to each carbon.
OK. So, let's do the aldol
part of the formose reaction.
So, in this reaction,
what we're going
to have is the same
starting material
up there are the same product up
there now as a starting material
for an aldol reaction, OK,
this is the second
part of the formose.
First part was up there,
that's the benzoin reaction,
second part has a--
doing a deprotonation.
This deprotonation is
likely stabilized by calcium
but I'm not going to show
the coordination to calcium.
So, if I had to say,
the addition
of calcium massively accelerates
this reaction but I'm going
to skip through that today.
This gives us a very popular
intermediate called an analyte.
And this analyte is
highly reactive, right?
So, we have analyte, we can
then line up another one
of these products from the
benzoin reaction up here.
And now do the famous
aldol reaction.
This is easily my favorite
reaction because 90 percent
or so of all the carbon
bonds that are found
in biology used this
aldol reaction, OK?
So, here is the product.
[ Noise ]
OK. And then in the last
step we can readily pick
up a proton from HA.
OK. So, this starts to give us
something that really does start
to look carbohydrate like.
[ Noise ]
OK. Questions?
OK. Pretty straight forward
series of steps using reactions
that we've seen before at least
that you saw back
when you took 51C.
If this aldol reaction is
unfamiliar to you, go back
and read about the
aldol reaction
in your reference
Organic Chemistry text.
It is essential that
you get comfortable
with the aldol reaction.
It is one we're going
to be using repeatedly
this quarter, OK?
This reaction here is going
to be an essential
reaction for you.
OK. Let's now see how we can
take these building blocks
and build it into something more
complicated, OK, no questions?
All right.
[ Noise ]
OK. So, there is
however a step here.
OK. So, you can build this
using the formose reaction
that I just showed you.
And then you go from
the aldehyde form
to this hemiacetal form.
Review carbohydrates
in your O chem book
if this reaction here
is unfamiliar to you.
But I'm hoping that everyone
is comfortable with this idea
that aldehydes have
either a ketone--
or sorry, carbohydrates have
either an aldehyde ketone form
or hemiacetal form, and this
hemiacetal form is the ring form
of the aldehydes.
Again, reread the
chapter on carbohydrates
if you're not ready for that,
by like chapter seven I
think we'll be into glycans
and carbohydrates
in a really big way.
OK. So, long before then, get
familiar with this concept
with the structures and
reactivities of carbohydrates.
OK. So, we can now
build the ribose rings,
we can peel the bases.
Let's put things together, OK?
So, in the first step, you could
do a glycosylation reaction
whereby you go from
this ribose ring
to actually having a base
attached to this ribose ring.
The key step to this reaction
is shown here in this key step,
there's an oxonium ion, OK?
So, these hemiacetals
can form an oxonium ion.
This oxonium ion is like a
positively charged carbonyl.
It is a fantastic electrophile
to which a nucleophile
can attack,
if the nucleophile happens to
be a base, say this adenine,
then the result will be
adenosine as shown here.
Furthermore, these things could
be stitched together into chains
that have a phosphodiester
backbone akin to what's seen
in RNA and DNA, actually not
akin, identical to what's seen
in RNA and DNA using
reactions that can be--
that can involve long polymers
of phosphate that are found
for example on calcium
phosphate crystals, OK?
So, phosphate is a
fascinating little molecule.
It forms all kinds of
interesting polymers
and crystals but in any case,
you can make the
triphosphate version
and the triphosphate version
could be then stitched together
into this oligomer.
It turns out using what I told
you, you can synthesize all
of the-- pretty much
all of the biopolymers
that are found in biology, OK?
That we can now-- you're
now ready to synthesize all
of the RNA bases, all the
RNAs attached to ribose.
It turns out that DNAs are a
little bit more complicated,
getting rid of that deoxy
is kind of a challenge
and to us chemists,
that raises a contrary
and at the same time
poses a solution.
OK. So, our thought is
that since we can readily
synthesize RNA, our thoughts are
that the very first biopolymer
to emerge on this planet,
might have been RNA and
it turns out that RNA a--
has sufficient reactivity to
really handle that role, OK?
So, for example, the proteins
that are being synthesized
by your cells right now are
being synthesized using RNA
as the catalytic biopolymer.
The RNA portion of your
ribosome is what's responsible
for translation of
RNA into proteins, OK?
So, RNA is an amazingly
capable molecule
and that's not a
totally crazy experiment.
We haven't talked about the
prebiotic synthesis of proteins.
It turns out that you can also
use very basic building blocks
and build amino acids and
there's a now classic experiment
that was done in the 1950s
called the Urey Miller
Experiment that I think
every one as learned
about it some point
in their lives.
But it basically consists of
having very simple precursors
and electrical spark
meant to mimic lightning.
And from this, you get out, you
can extract out amino acids.
In fact, I have to know this
was done at UC Irvine as-- an--
as a-- this was one of the
experiments that's done one
of the-- the teaching
labs, right?
Has anyone in the room
done this experiment?
Darn. They stop running that.
OK. That's too bad.
It's a really fun experiment
to do, I recommend it.
Maybe not in your
garage, but it works.
It actually works.
You can extract out
pretty readily amino acids
in great quantities.
Recently, the original samples
from the 1950s were found,
and then retested using more
modern analytical techniques
and in addition to amino
acids that are shown here.
You can actually find lots
of other amino acids as well.
OK. So, this involves a Strecker
synthesis of amino acids.
And I'm going to refer you
to a figure in the book
that actually depicts
the-- this mechanism.
The figure is 231
in the book, OK?
So, the mechanism
is in the book,
it's actually pretty
straight forward.
And is this on the
worksheet as well?
OK, good. OK.
So, you will have a chance
to do arrow pushing involving
amino acids synthesis.
I want you to do it.
I think it's really important.
I'd like you to be
ready to do it, OK?
But its familiar players,
aldehydes, hydrogen cyanides,
ammonia's new, but
everything else is familiar,
the reaction are very similar
to what I've shown you today.
And then finally, you can stitch
together amino acids using
into peptides and proteins
using this reactive molecule
as a peptide coupling agent
and this actually found
in volcanic vents, OK?
OK. I need to switch
gears though.
I want to talk to you about
noncovalent interactions.
We've been talking about
covalents interactions.
It's now time for us to talk
about that other super
duper important topic
of noncovalent bonding.
Pretty much, everything in
biology involves nonbinding,
nonbonding or what are called
noncovalent interactions.
So, these are crucially
important.
They also tend to
be very, very weak.
So, what we find is that small
differences in energy lead
to very big effects, OK?
So, this is for example,
an enzyme and it's going
to in a noncovalent way
bind to a starting material
and catalyze the transformation
of that starting
material into product.
It's never going to
form a covalent bond
to the starting material.
The substrate or starting
material, the reactant
of this reaction, no covalent
bond, yet, this transformation,
this catalysis has really
important implications
for the cell.
So, we definitely need
to understand how
noncovalent interactions work
because they really
dominate biology.
And to give you an idea
of the strengths of these,
these are on the order of
10 to 100 times less strong
that a covalent interaction, OK?
So, a simple covalent
bond might be 90 kcals
or so of bonding energy.
But, a noncovalent interaction
between receptor and ligand
over here or receptor
and ligand over here
or another receptor ligand,
it's going to have a delta G
for that noncovalent
interaction on the order
of maybe 10 kcals for all.
So, it's going to be
considerably weaker, OK?
And this makes a transient,
this means it's not
going to last forever.
Now, this kind of a spectrum
of bonding that we use
to describe interactions
between two molecules.
So, here is two molecules
cozying up next to each other.
They have a choice
of what they can do.
On the one hand, they can
decide to form covalent bonds
if they decide to
share electrons
and that's what we've
been talking about, OK?
That requires a HOMO
and a LUMO that are kind
of appropriately positioned
and matched the energy to allow
that reaction to take place.
That doesn't always
happen, right?
Not all molecules decides
to react with each other.
And so, at the other extreme
or much weaker interactions
involving charges,
if these two molecules
have charges on them,
then you will get
charge-charge interactions
or ionic interactions.
And then somewhere in
between the spectrum
of really strong interactions
to very weak are Van Der
Waals interactions, OK,
where the molecules
interact to each other
through London dispersion
forces.
OK. I'm going to talk to you
about equations that govern all
of those interactions, OK?
You guys ready?
Questions so far?
All right.
Here is an equation that
I like you to memorize
because it describes the terms
for noncovalent interactions,
OK?
So, noncovalent,
the energy involved
in a noncovalent interaction
is proportional to,
in the first term,
Coulomb's law, OK?
So, Coulomb's law is the energy
between two point charges, OK?
So, how much energy
is that worth?
How much do those guys want
to interact with each other?
How much potential
energy is available?
OK. So, if Q1 and Q2
are the same sign,
if they're both negative
charges, Q1 times Q2 is going
to give us a positive term here.
If, however, they're
opposite charges,
we'll get a negative
term and note
that negative terms means a
more stable interaction, OK?
So, energy over here is starting
up here and we want to go
down lower to be
more stable, OK?
The big goal in life
for molecules
like this is stability, OK?
That's what these
molecules crave.
That's what makes
them run to work, OK?
They are looking for a
more stable situation, OK?
They're like skiing down ski
slopes and they're looking
to get to the bottom
as readily as possible
or the bottom is
lower in energy.
In addition, there is a--
there are two other terms
which embody the Van
Der Waals interaction.
So, this one is a
charge-charge interactions,
this one includes
repulsive interactions
which are proportional to R--
the inverse R distance
between the two molecules raise
to the 12th power or
attractive interactions
where it's raised
to the 6th power.
And these numbers here
start to tell us quite a bit
about the distance dependence
of these different terms
where this one's
raised to the inverse 1,
inverse 12, inverse 6.
That makes a really
big difference.
OK. Let's dissect each of
these interactions in turn.
Let's start with
the charge-charge
interactions first.
Charge-charge interactions,
again, are governed
by this coulombic potential
where we have the charges
up here, and then we have
epsilon term over here.
This is the dielectric constant.
OK. This dielectric
constant is very environment
and context dependent.
So, in different
portions of the cell,
you might have different
salt concentrations
which dramatically
affects the strength
of this charge-charge
interaction, OK?
So, for example, if the two
charges happen to be present
where there's no water,
and there's no ions,
this term over here is
going to be a lot lower
and in turn that's going to make
the charge-charge interaction
much stronger, OK?
So, this is going to be very
dependent upon the surrounding
environment, OK?
Now, as we said earlier,
atoms with the opposite charge
are going to attract each other
and so in turn, this means that
the potential energy is going
to go down as the distance
between the two decreases.
On the other hand, atoms of
the same charge are going
to repel each other and that's
going to force them apart
as they get closer and
closer to each other.
Notice that this does not go
all the way down, you know,
to run into like some
ridiculously low number.
Eventually, you'll get, you
know, fusion between the atoms
and that doesn't happen,
that requires some insane
amount of potential energy.
So, its going to drop down here
and then all the sudden it's
going to blast out to the moon
over here and then draw
back down again, OK?
So, that's why we're leaving
off what happens over here.
OK. Last thought of the day,
formal charges are not the same
as the partial charges
that actually dominate
when we look at molecules, OK?
So, I've been drawing
formal charges all day.
It's a useful shorthand
but it doesn't tell you
exactly where the charge is.
And the location of the
charge is critically important
to determining really what the
coulombic interaction tells you,
OK?
So, for example here is some
Lewis structures over here.
Here is an ammonium ion.
It would be quite proper
to put the positive charge
on the nitrogen and have the
hydrogens just hanging out.
Here is a resident structure
for a ketone, acetone,
and when we actually look
at where the charges are
distributed, we find something
as kind of mind blowing,
really weird, OK?
So, rather than having neatly
a single positive charge,
just set the nitrogen.
Instead, what ends up
happening is these hydrogens end
up picking up a little
bit of positive charge
and the nitrogen ends up
with the negative charge.
Similarly, with the
ketone over here,
the situation is more
complicated as well,
and what's going on
here is a redistribution
of charge based upon
the reorientation
of the molecular orbitals
that govern this complicated
molecule over here.
So, when we come back next time.
We'll be looking at how those
molecular orbitals interact
with each other in other
noncovalent interactions.
And then we'll be
talking about DNA.
Have a good weekend.
[ Silence ]
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