Bioorganic Phosphorus: Forms of Phosphate

Uploaded by lamechivanes on 13.12.2010


We have encountered phosphorus
in a variety of organic functional groups
and transformations throughout the semester.
And in the last webcast we talked about the structure
of nucleic acids with their phosphodiester.
We want to go beyond structure in this series of webcasts
and actually pull together just about everything
that we’ve encountered with phosphorus chemistry
into one section.
And this is the section
on bioorganic phosphorus chemistry
– where unlike the last c- l- webcast
where our focus was on structure.
In this webcast our- our focus is going to be on reactivity.
And so the making for example of new bonds around phosphorus,
such as in the case of the formation of a strand of RNA,
[psk] that phosphodiester backbone is synthesized.
1i6h is the PDB code of RNA polymerase.
That’s the enzyme here that reads the DNA template
and uses that information as again it corkscrewed down
that DNA template.
Spitting out the new RNA strand
with the complimentary base pairing
that we talked about last time.
It’s the making of this phosphodiester backbone
that involves the reactivity that we’re interested in
in this webcast.
To get started talking about and bringing together
all of the bioorganic phosphorus chemistry,
let’s briefly look at the structure of phosphoric acid.
Phosphorus is in its oxidation state five,
phosphoric acid has three protons to lose,
they’re lost at pH- at a pKa, which has a ΔpKa
of about five units for each proton,
leading to the structure of this phosphate tri-anion.
The physiological form, the most common form
is the one that is the di-anion.
Just above physiological pH or right around physiological pH,
in fact what makes physiological pH buffered
is this orthophosphate group.
The ah tri-anion has a residence delocalized structure
I’ll let you look at these on your own,
but you can see that each of the oxygen atoms
can carry that negative charge.
There’s really no such thing
as a phosphorus-oxygen double bond,
all the bonds are equivalent,
we would draw the hybrid in this way
with partial negative charge,
not full negative charge on all four of the oxygen atoms.
So, it’s a fully resonance stabilized tri-anion.
[psk] Well, the successive increase in pKa
has to do with the build-up of negative charge,
resisting further the loss of the proton
because that will cause that negative charge to build up.
That’s the basic idea behind phosphorus-
the most important of the phosphorus building blocks.
And you can see-
and what’s most important about phosphorus
is that the functional groups
are going to phosphorus tetrahedral geometry,
centered around four oxygen atoms.
What we want to do next is begin to look at
variations of this
and we’re going to change the hydrogen atom
with an organic constituent.
If we only put one constituent on there,
that’ll be a phosphomonoester.
If we put two substituents on,
we’ll be talking about a phosphodiester,
as in the case of say RNA and DNA.
A phosphotriester um,
would have three of those hydrogens replaced
with organic constituents.
Let’s look at phosphomonoesters next.
We’ve encountered this already, for example,
when we talked about the shikimate pathway,
phosphoenol pyruvate showed up there.
And phosphoenol pyruvate has the ah, attachment
of this enol type group,
as an enol ether or an enol ester to phosphate-
to that phosphate group.
So it’s a phosphomonoester,
where that constituent is an enol.
We recently just encountered glucose 1-phosphate
which was a ah, good leaving group for glucose
making the glycosidic bond.
That bond is the bond that undergoes ah,
a bond breaking.
And I don’t really want you to pay too much attention to this,
but these are um, going to certainly be generally found
as they’re mono-anion or very often
as they’re dion- anion form.
That first proton is lost even more ah,
it’s a more powerful acid than is ah, phosphoric acid.
What I really want you to pay attention to
is what comes next
and that is the chemistry that takes place at phosphorus
and around phosphorus.
At phosphorus, hydrolysis can take place.
And if it takes place non-enzymatically,
so just in solution,
the process is thought to occur in a very SN2-like process.
So that what’s drawn in the brackets,
is actually a transition state-
a transition state where bonds are being made and broken.
This is not an intermediate, it’s ah,
in the act of bond-forming and bond-breaking.
And the key thing to note and the key thing to highlight
is the availability of this proton,
which can serve as an intramolecular general acid
to assist the breaking of that phosphorus oxygen bond.
So, as the nucleophile, in this case,
hydroxide approaches phosphorus,
this bond begins to weaken as it picks up the proton.
And you can see partial bond breaking
between that oxygen and that proton.
And upon making between that oxygen and the proton,
so that the leaving group is lost as the new alcohol
and the di-anion is created.
Notice charge neutrality is maintained
- negative charge, negative charge
and the di-anion on the product side.
So that’s the way that hydrolysis takes place.
And you’re going to notice that this SN2 like process,
for the phosphomonoester is much different
than the chemistry that takes place at phosphodiesters.
Phosphomonoesters, SN2, phosphodiesters -
they’ll take place by a different mechanism.

Chemistry can also take place around phosphorus,
not just at phosphorus.
So, at phosphorus is this hydrolysis reaction.
Around phosphorus, very much like we saw what takes place
in the case of glucose 1-phosphate,
there’s going to be a displacement
of that phosphorus-oxygen bond
where this serves as a leaving group.
It actually is a leaving group,
whose leaving group ability is comparable to a bromide.
For example, in an SN2 reaction
we can break that carbon-oxygen bond
and emitting that phosphate group as a leaving group.
So, SN2 chemistry can take place around phosphorus
with that phosphate group as a leaving group.