Comparison of the use of the MNDO and MINDO/3 methods with ab initio methods to study tautomerism in histamine, 2‐ and 4‐methylhistamine

The semiempirical MNDO and MINDO/3 methods are used to study the various tautomeric forms of histamine, 2‐methylhistamine, and 4‐methylhistamine. Comparisons of the optimized structures and tautomerization energies are made with values obtained from ab initio Hartree‐Fock calculations using the 3‐21G and STO‐3G basis sets. Based on these results and previous comparisons of STO‐3G results with x‐ray structures, the present results indicate that while there are some differences in the values of the structural parameters, the changes in structure upon tautomerization and/or protonation are very similar. Further analysis of the MNDO and MINDO/3 structures by means of their utilization in 3‐21G and STO‐3G calculations indicates that either of these semiempirical methods provides reliable values for the structural parameters. Both methods give good qualitative agreement with the ab initio calculations for the relative energies of the various tautomers in the three compounds. In these studies the MNDO method appears to give better quantitative agreement with the 3‐21G and STO‐3G results than the MINDO/3 method.