6
$\begingroup$

NAD+ and NADH

We could draw a resonance form with the pi electrons shifting, placing a positive charge on C-4, to which a $\ce{H+}$ along with 2 electrons are added. Thus we get an NADH molecule as shown in the picture.

If this is how the reaction happens, then why doesn't the hydrogen get added to C-2 (or C-6 which is equivalent)? There's also a resonance form where C-2 has a positive charge and could accept a hydride ion. Why doesn't this happen?

$\endgroup$
2
  • 3
    $\begingroup$ In a synthetic setting, they could add to C-2. But in the body, these reactions are mediated by enzymes which hold the reactants in a very specific orientation. I'd guess that the regioselective delivery of hydride to C-4 is controlled in that way. $\endgroup$ Jan 27, 2017 at 17:50
  • $\begingroup$ I'm sure that additions to pyridinium rings are well studied and should be well documented in the literature. $\endgroup$
    – Zhe
    Jan 27, 2017 at 18:53

1 Answer 1

6
$\begingroup$

Living organisms utilize protein based enzymes to catalyze otherwise unfavorable reactions under very mild conditions. They achieve this by bringing the substrates together in a very specific manner. Dehydrogenases are a class of oxidoreductases that oxidize substrates using NAD$^+$. Here is the active site of lactate dehydrogenase:

lactate reductase

As you can see, carbon-4 of the nicotinamide ring is oriented towards the substrate. The orientation of the molecules is why carbon-4 is selectively reduced.

$\endgroup$
0

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.