Cucurbit[7]uril-driven modulation of ligand-DNA interactions by ternary assembly.

The design of small organic molecules with a predictable and desirable DNA-binding mechanism is a topical research task for biomedicine application. Herein, we demonstrate an attractive supramolecular strategy for controlling the non-covalent ligand-DNA interaction by binding with cucurbituril as a synthetic receptor. With a combination of UV/vis, CD and NMR experiments, we demonstrate that the bis-styryl dye with two suitable binding sites can involve double stranded DNA and cucurbituril in the formation of the supramolecular triad. The ternary assembly is formed as a result of the interaction of macrocyclic cucurbituril with one pyridinium fragment of the bis-styryl dye, while the second pyridinium fragment of the dye is effectively associated with DNA backbones, which leads to a change in the ligand-DNA binding mode from aggregation to a minor groove. This exciting outcome was supported by molecular docking studies that help to understand the molecular orientation of the supramolecular triad and elucidate the destruction of dye aggregates caused by cucurbituril. These studies provide valuable information on the mechanisms of DNA binding to small molecules and recognition processes in bioorganic supramolecular assemblies constructed from multiple non-covalent interactions.

The regioselective [2 + 2] photocycloaddition reaction of 2-(3,4-dimethoxystyryl)quinoxaline in solution.

Herein, the [2 + 2] photocycloaddition between two molecules of (E)-2-(3,4-dimethoxystyryl)-quinoxaline (1) in an acetonitrile solution to form only one cyclobutane isomer out of eleven possible isomers is described. The observed photocycloaddition reaction is reversible; thus, the studied photocycloaddition reaction can be considered as a photoreversible photochromic process. The removal of two methoxy groups from the (E)-2-(3,4-dimethoxystyryl)quinoxaline (1) structure produces compound 2, which participates only in the photoisomerization reaction. The change of the quinoxaline residue in 1 to quinoline results in the formation of compound 3, which demonstrates the regioselective oxidization electrocyclic transformation through the formation of a novel C-N bond.

Regiospecific Photocyclization of Mono- and Bis-Styryl-Substituted N-Heterocycles: A Synthesis of DNA-Binding Benzo[c]quinolizinium Derivatives.

Regiospecific C-N photocyclization of mono- and bis-styryl-substituted N-heterocycles was investigated. We demonstrated that the C-N regiospecificity of the photoinduced electrocyclization is a general feature of ortho-styryl-substituted N-heterocycles comprising one and two nitrogen atoms. This phototransformation provides a straightforward synthesis of the pharmaceutically important benzo[c]quinolizinium cation and its aza-analogues. Noticeably, bis-styryl derivatives undergo only one-fold cyclization with the second styryl fragment remaining uninvolved in the cyclization process. Photocyclization products of monostyryl derivativatives intercalate into calf thymus DNA (ct DNA), whereas photocyclization products of bis-styryl derivativatives possess a mixed binding mechanism with ct DNA. The results can be used for development of novel DNA-targeting chemotherapeutics based on benzo[c]quinolizinium derivatives.

DNA-ligand interactions gained and lost: light-induced ligand redistribution in a supramolecular cascade.

A supramolecular five-component cascade is presented that enables light-controlled transport of an in situ modified ligand between three host systems based on the different complexation preferences of cyclodextrin, cucurbituril, and double-stranded DNA. The results point out novel approaches for the control of drug-DNA interactions in DNA-targeting therapy.

Regiospecific C-N photocyclization of 2-styrylquinolines.

Regiospecific C-N photocyclization of 2-styrylquinolines resulting in formation of potentially biologically active quino[1,2-a]quinolizinium derivatives was investigated. The presence of strong electron-donating groups in the phenyl ring reveals to be a crucial factor managing photocyclization effectiveness. Introduction of a crown ether moiety allows changing the photoreaction parameters by means of complexation with Mg(ClO4)2.