具有DNA切割活性的抗肿瘤抗生素连氮霉素中引人注目的空间S-O相互作用。

Attractive through-space S-O interaction in the DNA-cleaving antitumor antibiotic leinamycin.

作者信息

Wu S, Greer A

机构信息

Department of Chemistry, Graduate School and University Center & The City University of New York (CUNY), Brooklyn College, Brooklyn, New York 11210, USA.

出版信息

J Org Chem. 2000 Aug 11;65(16):4883-7. doi: 10.1021/jo000145o.

DOI:10.1021/jo000145o

PMID:10956467

Abstract

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.

摘要

我们在此描述了一项关于抗肿瘤抗生素链黑菌素1中分子内非键合1,5-硫-氧（S-O）相互作用的研究。对链黑菌素1以及模型体系2-5进行密度泛函理论和半经验计算的结果，为1,5-S-O非键合相互作用提供了证据。我们的结果用于解释先前关于链黑菌素1的X射线结构的实验数据（平山，N.；松泽，E. S. 《化学通讯》，1993年，1957页）。酰胺氧（O5）改变了硫代亚磺酸酯的构象，并稳定了1,2-二硫杂环戊烷-3-酮1-氧化物杂环。这种吸引相互作用促使链黑菌素的S1采取扭曲的三角双锥几何构型。这种稳定相互作用的强度约为6千卡/摩尔。