Attractive through-space S-O interaction in the DNA-cleaving antitumor antibiotic leinamycin.
We describe here a study on the intramolecular nonbonded 1, 5-sulfur-oxygen (S-O) interaction in the antitumor antibiotic leinamycin 1. The results from density-functional theoretical and semiempirical calculations on leinamycin 1 and model systems 2-5 provide evidence for the 1,5-S-O nonbonded interaction. Our results are used to explain previous experimental data on the X-ray structure of leinamycin 1 (Hirayama, N.; Matsuzawa, E. S. Chem. Lett. 1993, 1957). The amide oxygen (O5) alters the thiosulfinate ester conformation and stabilizes the 1,2-dithiolan-3-one 1-oxide heterocycle. The attractive interaction induces S1 of leinamycin to adopt a distorted trigonal bipyramidal geometry. The magnitude of this stabilizing interaction is approximately 6 kcal/mol.
Wu
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Department of Chemistry, Graduate School and University Center & The City University of New York (CUNY), Brooklyn College, Brooklyn, New York 11210, USA.
Greer
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D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D007769:Lactams; D018942:Macrolides; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013844:Thiazoles; D013871:Thiones
D000903:Antibiotics, Antineoplastic; D007769:Lactams; D018942:Macrolides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin