today we're going to talk about a
molecule which really changed the world
it's called penicillin and today well it
happens to be penicillins 82nd birthday
which is completely by chance we didn't
plan this well on September the 28th
1928
so Alexander Fleming was working in
hospital in London he'd just come back
off his holidays
I need previous before Gyllenhaal he
left some works or some agar plates or
culture plate or he's playing around
with bacteria and he came back and he
noticed what he's doing is washing up
that one of the plates had a mold growth
on it and around the mold growth there
was no presence of bacteria whereas the
rest of the plate had bacteria on it and
he had a Eureka moment he said my
goodness I've just found as an
antibiotic so what it is it's a really
interesting natural product I mean it's
beautiful in its construction you think
about some really interesting features
got this square ring here with an oxygen
double bond to a knight to a carbon to a
nitrogen this is called a beta lactam
and the beta lactam beyond antibiotics
are very well known now this is the
first one really and then we got this
five membered ring here there's a sulfur
there and it's a carboxylic acid group
here's like an acid a carbon to a double
bond oxygen and a cabin to a single bond
with a hydrogen office that's a
carboxylic acid so that's penicillin I
like to think of penicillin as a
molecular mousetrap so when bacteria
evade a host they replicate that means
they more than reproduce and to do that
they need machinery so like a builder
build the house puts bricks together
bacteria produce enzymes and easie like
the builders the building and they used
bits in building materials like bricks
and the enzyme sticks things together
like build this house so bacteria have
instead of walls that well brick walls
they have cell walls now in the cell
wall construction they have an enzyme
like the Builder and stitches together
building blocks and one of these
building blocks is this amino acid
sequence alanine alanine so but don't
need to worry exactly the structure of
that well what happens penicillin is
going to fool the enzyme because if you
look here well if you can get it right
this part of a is alanine alanine is
here in this penicillin molecule too or
very similar so it fools the enzyme the
enzyme comes along like a mousetrap
it smells the cheese it feels it here
because yeah like that it goes to eat
the cheese and all of a sudden this
beautiful four membered ring
opens up pop and eats the enzyme
essentially it stops the enzyme from
working so it traps it out irreversibly
stops it from working the Builder has to
down tools and the implication is that
the cell wall has not been completely
constructed properly so it's quite weak
so the bacteria has its pressure inside
it and all of a sudden pop bacteria
explodes the cell wall collapses and it
dies it can't replicate anymore so
that's how penicillin works it's a real
neat mechanism once we discovered the
structure of penicillin then it became
the synthetic chemists job to find out
ways to make it because okay so okay
having one molecule but let's try and
modify it so if you look at the
structure we can modify here we can
change this bit of the molecule
perhaps we can change this part of the
molecule here but we really want to keep
this course drop just four membered ring
with the beta-lactam ring which we call
it is really important so we can't get
rid of that really that's the spring in
the mousetrap yeah
so it turns out after a lot of hard work
we figured out ways to make it and in
modern days we've made a heck of a lot
of variants or derivatives in using
medicinal chemistry and here's one
example
it's amoxicillin now perhaps you've
heard of this this is a really powerful
antibiotic it's broad-spectrum that
means attack slots or kills lots of
different types of bacteria one of the
technicians in the labs of Florey and
chain who were two scientists who helped
develop the penicillin story now he had
an eye infection apparently he had to go
to a shooting competition so the
scientists decided let's try out our
special mold juice this is before the
new is penicillin of course and they put
it in his eyes and he found out that
yeah hey presto his eye infection
disappeared so I said I think that's a
quite a funny story I wouldn't try that
in a lab technician these days I don't
think would be allowed well cost
thousands of years ago hundreds of years
ago we could didn't have the technology
to make the molecules or know what
that's going on but the
Egyptians apparently used to treat their
sores on their arms or their body with
moldy bread now the bread has been
affected by a mold and probably a
penicillin mold maybe I'm speculating
but I'm guessing something like that
what produced the natural product like
penicillin
and it treated the infection so you can
think there's no smoke without fire so
it's interesting that hundreds of years
later we actually know on a molecular
level what's going on it's a molecule
that really changed society I mean
people were dying of infections hundred
years ago in early Victorian times the
average life was a expectancy was about
45 I think I mean this molecule really
extended human - allowed us to allow the
infections that would kill you at one
time to be treated and people could live
a healthy life I mean just one molecule
did that I think it's spectacular and it
just shows you the power of chemistry
and what can be achieved mean who knows
what's going to be achieved in a future
with chemistry I mean it's just I think
that's just exciting in itself