CCL: Help for partial charge of nitrogen atoms in pyrimidine, pyridine and pyrazine

Hello, Dear CCL'rs:

I calculated CHELPG partial charge on nitrogen atoms in pyridine, pyrimidine and pyrazine (also 4-azaindole, 4,6-diazaindole and 4,7-diazaindole) for later binding free energy caculation.

Based on their pKa and inductive effect, I would expect that the electron density on nitrogen atoms in pyrimidine or 4,6-diazaindole would be smaller than those in pyridine/4-azaindole.  (correct me if I am wrong) However, I got larger partial charge on nitrogen atoms in pyrimidine from gaussian calculation:



compound                CHELPG partial charge on Nitrogen                    pKa

pridine                                  -0.6043                                                5.1

pyrimidine                           ~ -0.77                                                 1.3

pyrazine                               -0.4395                                                0.6

I used B3LYP/6-31G(d) basis set in the above calculation. I had tried several other basis sets and charges (Mulliken and Merz-Kollman), and obtained the same obseration. Is my assumption wrong? Please share your experience with me. Thanks in advance for you help!

Best wishes,

Minghu Song

Locus Pharmaceuticals