A Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line.

DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity.

Development of 4,4'-dibromobinaphthalene analogues with potent photo-inducible DNA cross-linking capability and cytotoxicity towards breast MDA-MB 468 cancer cells.

Photoinduced DNA cross-linking process showed advantages of high spatio-temporal resolution and control. We have designed, synthesized, and characterized several 4,4'-dibromo binaphthalene analogues (1a-f) that can be activated by 350 nm irradiation to induce various DNA damage, including DNA interstrand cross-links (ICL) formation, strand cleavages, and alkaline labile DNA lesions. The degree and types of DNA damage induced by these compounds depend on the leaving groups of the substrates, pH value of the buffer solution, and DNA sequences.

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

Five novel 1,1'-binaphthalene analogues - 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 - 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.

Design, Synthesis, and Characterization of Binaphthalene Precursors as Photoactivated DNA Interstrand Cross-Linkers.

Most recently, alkylation via photogenerated carbocations has been identified as a novel mechanism for photoinduced DNA interstrand cross-link (ICL) formation by bifunctional aryl compounds. However, most compounds showed a low efficiency for DNA cross-linking. Here, we have developed a series of new 1,1'-binaphthalene analogues that efficiently form DNA ICLs upon 350 nm irradiation via generated 2-naphthalenylmethyl cations.

Hydrogen peroxide activated quinone methide precursors with enhanced DNA cross-linking capability and cytotoxicity towards cancer cells.

Quinone methide (QM) formation induced by endogenously generated HO is attractive for biological and biomedical applications. To overcome current limitations due to low biological activity of HO-activated QM precursors, we are introducing herein several new arylboronates with electron donating substituents at different positions of benzene ring and/or different neutral leaving groups. The reaction rate of the arylboronate esters with HO and subsequent bisquinone methides formation and DNA cross-linking was accelerated with the application of Br as a leaving group instead of acetoxy groups.

Photochemical Generation of Benzyl Cations That Selectively Cross-Link Guanine and Cytosine in DNA.

UV irradiation of several aryl boronates efficiently produced bifunctional benzyl cations that selectively form guanine-cytosine cross-links in DNA. Photoinduced homolysis of the C-Br bond took place with the aryl boronate bromides 3a and 4a, generating free radicals that were oxidized to benzyl cations via electron transfer. However, photoirradiation of the quaternary ammonium salts 3b and 4b led to heterolysis of C-N bond, directly producing benzyl cations.

Photoinduced DNA Interstrand Cross-Link Formation by Naphthalene Boronates via a Carbocation.

Most photoinduced DNA cross-link formation by a bifunctional aryl derivative is through a bisquinone methide. DNA cross-linking via a bisarylcarbocation remains a less explored area. We designed and synthesized a series of naphthalene boronates that produce DNA interstrand cross-links via a carbocation upon UV irradiation.

Chiral surfactant-type catalyst: enantioselective reduction of long-chain aliphatic ketoesters in water.

A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2.