Studies on the circular dichroism of penam and penam sulfoxides

Abstract

Optical rotatory properties of models of 6-aminopenicillanic acid (6-AP A) as obtained from earlier molecular orbital and rotatory strength calculations are corroborated by new CD data for 6-AP A. The new spectra extend down to 180 nm, revealing a positive Cotton effect near 185 nm due to carbonyl π→π * transitions. The pH sensitivity of the optical activity of the β-lactam amide π→π * and the 203-nm n→π * transitions is explainable in terms of electrostatic effects and orbital interactions present in α-aminoketones and 4-membered rings which tend to flatten out the NH 2 group. These same interactions are responsible for the unusually low p K a of 4.75 for the amino group; (the carboxyl group of 6-AP A has a normal p K a of 2.5). The previous calculational procedures are extended to the sulfoxides of 6-AP A, and the predicted CD spectra are compared to new experimental curves and also to available data for penicillin sulfoxides. The MO's associated with the principal bands are illustrated with the aid of electron density maps. The positive Cotton effect observed and calculated near 230 nm is due to two charge transfer transitions within the asymmetric penam nucleus. Similar to the situation with the unoxidized penams, the sulfoxide of 6-AP A displays a very low p K a for the amino group (3.8) and a change toward a less positive CD band at 202 nm upon protonation of this group.