pKa and Delta E

DRdotBEE

Hey everyone,

Im doin a drug design module and we used gaussian 03w to find the delta E of nevirapine and a protonated version of nevirapine. We were then asked to use this to calculate the pKa.... but i'm not sure how.

I've tried using the delta G of the system but it doesn't match any literature values! help please!

Dr.Bee

SOL

Delta G = RTLnK so if you know what temperature your model is supposed to be at then you should be able to calculate K right?

DRdotBEE

Yea using delta G = -RTlnK but using that K value for the pKa gives an answer = -0.04.....

whereas lit. says it is about 2.8, I don't know if this is a fault in the gaussian calculations or what. thanks for the post though

Well this is just a guess, I could be really really wrong.

The delta E was taken from the sum of electronic and thermal energies?
You can use the energies to calculate the enthalpy of the change from one to the other. Then put enthalpy, temperature etc into



I think, and then take the minus log of K to get pKa?

Gaussian measures in Hartrees if I remember right, so you'll probably have to convert to kJ/mol

DRdotBEE

Thanks for that,

I'm pretty sure our lecturer has somehow led us astray. The figures from gaussian even after conversion to KJ/mol (you were very correct) don't match any literature values (all lying at 2.8 ish)

All the theory you've posted makes sense though.

I asked the lecturer today and he just said work the relative basicity out from the delta G value of the protonation reaction (the more negative the more basic)

I think its his attempt to cover up his numerical errors.

Thanks for all the help though!