posted on 2021-03-09, 06:32authored byBrett
C. Bookser, Quyen-Quyen Do, Yongsak Sritana-Anant, Kim K. Baldridge, Jay S. Siegel
The polar−π effect on
tetrazoles, medicinal chemistry
isosteres of carboxylate, is tested by a Hammett pKa (microtitration) analysis over a series of 5-(m-terphenyl-2′-yl)-1H-tetrazoles.
A comparison with m-terphenyl-2′-yl-carboxylic
acids supports the isostere analogy also in response to environmental
changes. Computational (B97D/def2TZVPPD) extension of the series plus
a scan of solvents (vacuum to water) demonstrates the trend with the
dielectric constant. The effect is energetically small but may make
statistically significant contributions to the tetrazole pharmacological
profile.