13- Lactam physicochemical studies

Boyd DB. Theoretical and physicochemical studies on P-lactam antibiotics. In Morin RB, Gorman M, eds. P-Lactam Antibiotics Chemistry and Biology. Vol. 1. New York Academic Press, 1982 437-545. 

D. B. Boyd, in Beta-Lactam Antibiotics Chemistry and Biology, Vol. 1. R. B. Morin and M. Gorman, Eds., Academic Press, New York, 1982, pp. 437-545. Theoretical and Physicochemical Studies on Beta-Lactam Antibiotics. 

V. Other Physicochemical Studies of B-Lactams and Relevant Structures 500... 

The accumulating evidence from both theoretical and other physicochemical studies of p-lactam antibiotics points toward the importance of the reactivity of the p-lactam ring as one determinant of antibacterial activity. The relationship between reactivity and activity is seen in the structural data from X-ray analysis, in hydrolysis rate measurements, and in computer experiments on theoretical reactivity. 

The physicochemical properties of azacytosines, and the corresponding azacytidines and their derivatives have been studied.116-123 It was shown by IR, NMR, and UV spectroscopy116-118,123 that 6-azacytosine, iV,IV-dimethyl-6-azacytosine, and their 1-methyl derivatives as well as 6-azacytidine, possess the lactam-amine form 14, like cytosine itself. Similar studies118 have shown that 3-methyl-6-azacytosine possesses the lactam-imine form 6, in contrast to 3-methylcytosine, which has the lactam-amine form 3.102... 

In summary, the pattern recognition studies indicate that the reactivity of the p-lactam ring is a crucial determinant of the in vitro antibacterial activity of a related series of cephalosporins. Physicochemical properties that do not reflect reactivity appear to be less useful indicators of activity. 

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