Abstract

CRITICAL REVIEW ON COMPUTATIONAL STUDY OF THE PROTONATION ON PHENOXYMETHYLPENICILLIN TAUTOMERS BY AUSTIN MODEL-1 METHOD

Bojja Rajeshwar Rao*

ABSTRACT

Significance of β-Lactam ring of penicillin has been identified to block the activity irreversible and their derivatives studied extensively as broad anti-microbial spectra to reducing undesirable side effects. Isolation of the important intermediate, 6-aminopenicillanic acid from enzymatic splitting of natural penicillin’s (G & V) was led the preparation of several semi-synthetic penicillins. The tautomerism of phenoxymethylpenicillin reveals with the shifting of hydrogen atom from α-carbon atom of β-lactam (-HC-C=O) group to the oxygen atom for the formation of enol (-C=C-O-H) group or shifting of hydrogen atom from nitrogen atom of lactam (-HN-C=O) group to the oxygen atom for the formation of lactim (-N=C-O-H) group. The geometry, conformation and electronic structure of phenoxymethylpenicillin(1) with its lactim (2), enol (3) and lactim-enol (4) systems and their protonated systems were optimized and calculated by semi-empirical molecular orbital AM1 method which includes experimental parameters and extensive simplification of the Schrodinger’s equation (HΨ=EΨ) for calculation of various properties in the gas phase. In this way quantum chemistry simulates chemical structure and reactions numerically and allows studying chemical phenomena by running calculations on computer rather than by examining reactions experimentally. In this connection, the heats of formation (ΔHfo), dipole moment (μ), quantum chemical descriptors and full atomic charges have been discussed. It is observed that all tautomers exist within the range of heats of formation (ΔHfo) as -90.6115 to -118.4089 kcal/mol and dipole moment (μ) as 2.3445 to 2.8946 D. The conformational analyses of mono-, di-protonated and anions of phenoxymethylpenicillin have also been evaluated.

Keywords: AM1, phenoxymethylpenicillin, chemical descriptors, tautomerism, induction effect, frontier molecular orbital energy.