博来霉素激活态向铁（Ⅲ）博来霉素的低温光解作用

Cryogenic photolysis of activated bleomycin to ferric bleomycin.

作者信息

Burger Richard M, Usov Oleg M, Grigoryants Vladimir M, Scholes Charles P

机构信息

Public Health Research Institute, 225 Warren Street, Newark, New Jersey 07103-3535, USA.

出版信息

J Phys Chem B. 2006 Oct 19;110(41):20702-9. doi: 10.1021/jp064906o.

DOI:10.1021/jp064906o

PMID:17034262

Abstract

Activated bleomycin (ABLM) is a drug--Fe(III)-hydroperoxide complex kinetically competent in DNA attack (via H4' abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(III).BLM) is poorly characterized because no observable intermediate product accumulates. Light was shown to trigger ABLM attack on DNA in liquid at -30 degrees C, so ABLM was irradiated (at its 350 nm ligand-to-metal charge-transfer transition) at 77 K to stabilize possible intermediates. ABLM photolysis (quantum yield, Phi = 0.005) generates two kinds of product: Fe(III).BLM (with no detectable intermediate) and one or more minor (1-2%) radical O-Fe-BLM byproduct, photostable at 77 K. Adding DNA, even without its target H4', increases the quantum yield of ABLM conversion >10-fold while suppressing the observed radical yield. Since cryogenic solid-phase reactions can entail only constrained local rearrangement, the reaction(s) converting ABLM to Fe(III).BLM must be similarly constrained.

摘要

活化博来霉素（ABLM）是一种药物——铁（III）-氢过氧化物复合物，在动力学上能够攻击DNA（通过夺取H4'）。这种中间体相对稳定，但其自发转化为铁博来霉素（Fe(III).BLM）的过程却缺乏充分的表征，因为没有可观察到的中间产物积累。研究表明，在-30℃的液体中，光会引发ABLM对DNA的攻击，因此在77K下对ABLM进行辐照（在其350nm的配体到金属的电荷转移跃迁处）以稳定可能的中间体。ABLM光解（量子产率，Φ = 0.005）产生两种产物：Fe(III).BLM（没有可检测到的中间体）和一种或多种次要的（1-2%）自由基O-Fe-BLM副产物，在77K下光稳定。即使没有其靶标H4'，加入DNA也会使ABLM转化的量子产率提高10倍以上，同时抑制观察到的自由基产率。由于低温固相反应只能进行有限的局部重排，将ABLM转化为Fe(III).BLM的反应也必然受到类似的限制。