T. Koetzle, G. Williams
Apr 14, 1976
Citations
6
Influential Citations
77
Citations
Quality indicators
Journal
Journal of the American Chemical Society
Abstract
Neutron diffraction data from a colorless 58 mg single crystal of trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (C/sub 14/H/sub 18/N/sub 4/O/sub 3/) were used to obtain a high-precision description of the structure. Crystallographic data: space group P anti 1, a = 10.523 (4) A, b = 11,222 (4) A, c = 8.068 (3) A, ..cap alpha.. = 101.22(1)/sup 0/, ..beta.. = 112.15 (1)/sup 0/, ..gamma.. = 112.65 (2)/sup 0/, Z = 2. A multisolution method was used to solve the phase problem and the structure was refined by least-squares techniques on F/sub 0//sup 2/ (all 4039 reflections) with parameters grouped in two blocks to yield agreement factors, R = 0.045 and R/sub w/ = 0.071. The 2,4-diaminopyrimidine tautomer is confirmed. The bases form an extended hydrogen-bonded ribbon with N(1) and N(2) acting as acceptor and donor respectively across one center of symmetry. Atoms N(3) and N(4) interact similarly across another inversion center. This hydrogen-bonding pattern supports a previously postulated model for binding of the drug to the receptor. No base-stacking interactions of the pyrimidine rings were observed and so no conclusions could be reached regarding the role of this associative mode in the receptor binding. A conformational energy calculation indicates considerable rotational freedom aboutmore » the two bonds linking the aryl groups. The trimethoxybenzyl systems do not participate in any specific nonbonded interactions. (auth)« less