Work

Photo-Reactivity of Binaphthalene Triphenylphosphonium Salts: DNA Interstrand Cross-Link Formation and Substituent Effects

Year: 2022

Type: article

Abstract: Five novel 1,1′-binaphthalene analogues 1a – 1e with triphenylphosphonium (TPP + ) salts as a leaving group have been synthesized and characterized as photo-activatable DNA alkylating agents. Phototriggered release of the TPP + group from 1a – 1e generated naphthalenylmethyl-free radicals that were spontaneously transformed to the corresponding cations directly producing DNA interstrand cross-link (ICL) formation via alkylation. The substituents at position 4 not only affect the efficiency of ICL formation but also influence the reaction rate for DNA cross-linking. Groups with small or medium size favor ICL formation, while a bulky substituent (e.g., phenyl group) prevents DNA interstrand cross-linking. DNA alkylation by the naphthalenylmethyl cations photo-generated from 1a – 1e occurs at dG, dC, and dA, while interstrand cross-linking took place with dG/dC base pairs. The TPP + salts ( 1a – 1e ) are cations with both lipophilic and hydrophilic properties, which have great potential for biological applications.

Source: Chemical Research in Toxicology

DOI: 10.1021/acs.chemrestox.1c00401

Authors: Qi Zhang, Zechao Lin, Xiaohua Peng

Institution: University of Wisconsin–Milwaukee

Language: English

Topic: Synthesis and pharmacology of benzodiazepine derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: University of Wisconsin-Milwaukee, Greater Milwaukee Foundation, National Institutes of Health, National Cancer Institute

Awards: G126510830, G2624940905, Novel DNA cross-linking agents and combination strategies for tumor-specific activation, New Radiation-Activated Antitumor Agents That Target Hypoxia