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 fro m density-functional theoretical and semiempirical calculations on leinamyc in 1 and model systems 2-5 provide evidence for the 1,5-S-O nonbonded inter action. 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 conformat ion and stabilizes the 1,2-dithiolan-3-one 1-oxide heterocycle. The attract ive interaction induces S1 of leinamycin to adopt a distorted trigonal bipy ramidal geometry. The magnitude of this stabilizing interaction is similar to 6 kcal/mol.