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Conformation/Tautomerization effect on the pK a values of lumazine and 6‐thienyllumazine
Author(s) -
Afaneh Akef T.,
Schreckenbach Georg
Publication year - 2014
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3320
Subject(s) - tautomer , chemistry , conformational isomerism , deprotonation , computational chemistry , density functional theory , aqueous solution , solvation , triazine , stereochemistry , crystallography , ion , molecule , organic chemistry
Density functional theory [B3LYP/6‐311+G(d,p)] was used in combination with the conductor‐like polarizable continuum model (CPCM) solvation model to investigate the relative stability and site‐specific p K a ijvalues of neutral and ionized tautomers of lumazine (LM) and 6‐thienylLM (TLM). Two types of populations should be taken into consideration when calculating the p K a ij , tautomers, and conformers. The major tautomer of neutral LM in aqueous solution is 13‐LM (the 13 notation refers to the acidic protons being in positions 1 and 3 of LM) TLM has decreased acidity at N 8 relative to LM. Further, the trans conformer of TLM is more acidic than cis . Similar to the case of LM, for TLM, N 1 is more acidic than N 3 in the uracil part. However, N 8 is predicted to be a stronger acid than N 1 for TLM. This acidity enhancement is essentially because of a specific stabilization of the anion when the thienyl group replaces H. Two factors are responsible for the acidity strength of N 8 : The thienyl ring upon deprotonation acts inductively as an electron‐withdrawing group, and the excess electron density is dispersed better when the system is trans and contains second‐row atoms. Accurate pK a calculation requires that all conformers/tautomers be included into the calculation. Copyright © 2014 John Wiley & Sons, Ltd.