Non-canonical DNA structures are widely used for regulation of gene expression, in DNA nanotechnology and for the development of new DNA-based sensors. I-motifs (iMs) are two intercalated parallel duplexes that are held together by hemiprotonated C-C base pairs. Previously, iMs were used as an accurate sensor for intracellular pH measurements. However, iM stability is moderate, which in turn limits its in vivo applications. Here, we report the rational design of a new substituted phenoxazine 2′-deoxynucleotide (i-clamp) for iM stabilization. This residue contains a C8-aminopropyl tether that interacts with the phosphate group within the neighboring chain without compromising base pairing. We studied the influence of i-clamp on pH-dependent stability for intra- and intermolecular iM structures and found the optimal positions for modification. Two i-clamps on opposite strands provide thermal stabilization up to 10–11°C at a pH of 5.8. Thus, we developed a new modification that shows significant iM-stabilizing effect both at strongly and mildly acidic pH and increases iM transition pH values. i-Clamp can be used for tuning iM-based pH probes or assembling extra stable iM structures for various applications.

Despite the significance of H₂O₂-metal adducts in catalysis, materials science and biotechnology, the nature of the interactions between H₂O₂ and metal cations remains elusive and debatable. This is primarily due to the extremely weak coordinating ability of H₂O₂, which poses challenges in characterizing and understanding the specific nature of these interactions. Herein, we present an approach to obtain H₂O₂–metal complexes that employs neat H₂O₂ as both solvent and ligand. SnCl₄ effectively binds H₂O₂, forming a SnCl₄(H₂O₂)₂ complex, as confirmed by ¹¹⁹Sn and ¹⁷O NMR spectroscopy. Crystalline adducts, SnCl₄(H₂O₂)₂·H₂O₂·18-crown-6 and 2[SnCl₄(H₂O₂)(H₂O)]·18-crown-6, are isolated and characterized by X-ray diffraction, providing the complete characterization of the hydrogen bonding of H₂O₂ ligands including geometric parameters and energy values. DFT analysis reveals the synergy between a coordinative bond of H₂O₂ with metal cation and its hydrogen bonding with a second coordination sphere. This synergism of primary and secondary interactions might be a key to understanding H₂O₂ reactivity in biological systems.

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar ¹O₂ generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C_4-6 alkyl (SARS-CoV-2) and C_6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C_8-10 congeners and a significant aggregation tendency for the C₁₂ derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.