Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen‐Dependent Photodynamic Cancer Therapy

Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene‐derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light‐sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV‐generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light.     

Nanoscopic Visualization of Soft Matter Using Fluorescent Diarylethene Photoswitches

The in situ imaging of soft matter is of paramount importance for a detailed understanding of functionality on the nanoscopic scale. Although super‐resolution fluorescence microscopy methods with their unprecedented imaging capabilities have revolutionized research in the life sciences, this potential has been far less exploited in materials science. One of the main obstacles for a more universal application of super‐resolved fluorescence microscopy methods is the limitation of readily available suitable dyes to overcome the diffraction limit. Here, we report a novel diarylethene‐based photoswitch with a highly fluorescent closed and a nonfluorescent open form. Its photophysical properties, switching behavior, and high photostability make the dye an ideal candidate for photoactivation localization microscopy (PALM). It is capable of resolving apolar structures with an accuracy far beyond the diffraction limit of optical light in cylindrical micelles formed by amphiphilic block copolymers.     

Design,Synthesis, and Application of an Optimized Monofluorinated Aliphatic Label for Peptide Studies by Solid‐State 19F NMR Spectroscopy

A conformationally restricted monofluorinated α‐amino acid, (3‐fluorobicyclo[1.1.1]pentyl)glycine (F‐Bpg), was designed as a label for the structural analysis of membrane‐bound peptides by solid‐state ¹⁹F NMR spectroscopy. The compound was synthesized and validated as a ¹⁹F label for replacing natural aliphatic α‐amino acids. Calculations suggested that F‐Bpg is similar to Leu/Ile in terms of size and lipophilicity. The ¹⁹F NMR label was incorporated into the membrane‐active antimicrobial peptide PGLa and provided information on the structure of the peptide in a lipid bilayer.     

Ab initio comprehensive conformational analysis of 2'-deoxyuridine, the biologically significant DNA minor nucleoside, and reconstruction of its low-temperature matrix infrared spectrum

A comprehensive conformational analysis of isolated 2'-deoxyuridine (dU), a minor DNA nucleoside, has been performed by means of ab initio calculations at the MP2/6-311++G (d,p)//DFT B3LYP/6-31G (d,p) level of theory. At 298.15 and 420 K, all 94 allowed conformers of dU are within 8.96 and 7.91 kcal/mol Gibbs energy ranges, respectively. Syn orientation for the base and South (S) conformers for the sugar dominate at 298.15 K: syn/anti=62.3%:37.7% and S/N=77.2%:22.8%. At 420 K in the majority of conformers, the base is anti oriented and the population of North (N) sugars increases: syn/anti=39.3%:60.7% and S/N=63.0%:37.0%. Values of all conformational parameters and correlations between them, as well as their correlations with valence bonds, and also correlations between valence bonds and angles were estimated. In general, 14 types of intramolecular H-bonds were detected (1-3 H-bonds per conformer, the total number 175), namely, C1'H...O2 (16 H-bonds), C2'H1...O5' (9), C2'H2...O2 (21), C3'H...O2 (21), C5'H1...O2 (14), C5'H2...O2 (11), C6H...O4' (37), C6H...O5' (22), C3'H...HC6 (4), O5'H...HC6 (2), O3'H...O5' (5), O5'H...O4' (1), O5'H...O3' (4), and O5'H...O2 (8). Geometric, vibrational, structural-topological, and energetic features of the OH...O intramolecular H-bonds in dU conformers were determined. The close similarity between energetic and geometric characteristics of dU and thymidine DNA-like conformers in anti and relevant syn conformations and their transition states of the anti-->syn interconversion implies that mismatch DNA glycosylase discriminates between the two nucleosides, mainly because of the difference in the shapes of their bases. Convolution of calculated IR spectra of all the dU conformers within the limits 3400-3700 cm(-1) appears to be consistent with its low-temperature matrix IR spectrum (Ivanov et al. Spectrochim. Acta, Part A 2003, 59, 1959), wavenumber discrepancy not exceeding 1%. It was concluded that, for a reliable reproduction of the experimental spectrum, the whole set of conformers should be taken into consideration. The suggested method makes reconstruction of the isolated nucleoside IR spectrum at a physiological interval of temperature reasonably possible.     

Excited-state intramolecular proton transfer distinguishes microenvironments in single- and double-stranded DNA

Herein, the efficient interaction of an environment-sensitive fluorophore that undergoes excited-state intramolecular proton transfer (ESIPT) with DNA has been realized by conjugation of a 3-hydroxychromone (3HC) with polycationic spermine. On binding to a double-stranded DNA (dsDNA), the ratio of the two emission bands of the 3HC conjugates changes up to 16-fold, so that emission of the ESIPT product increases dramatically. This suggests an efficient screening of the 3HC fluorophore from the water molecules in the DNA complex, which is probably realized by its intercalation into dsDNA. In sharp contrast, the 3HC conjugates show only moderate changes in the dual emission on binding to a single-stranded DNA (ssDNA), indicating a much higher fluorophore exposure to water at the binding site. Thus, the 3-hydroxychromone fluorophore being conjugated to spermine discriminates the binding of this polycation to dsDNA from that to ssDNA. Consequently, ESIPT-based dyes are promising for monitoring the interaction of polycationic molecules with DNA and probing the microenvironment of their DNA binding sites.     

Design of Furan-Based Acceptors for Organic Photovoltaics

We explore a series of furan-based non-fullerene acceptors and report their optoelectronic properties, solid-state packing, photodegradation mechanism and application in photovoltaic devices. Incorporating furan building blocks leads to the expected enhanced backbone planarity, reduced band gap and red-shifted absorption of these acceptors. Still, their position in the molecule is critical for stability and device performance. We found that the photodegradation of these acceptors originates from two distinct pathways: electrocyclic photoisomerization and Diels–Alder cycloaddition of singlet oxygen. These mechanisms are of general significance to most non-fullerene acceptors, and the photostability depends strongly on the molecular structure. Placement of furans next to the acceptor termini leads to better photostability, well-balanced hole/electron transport, and significantly improved device performance. Methylfuran as the linker offers the best photostability and power conversion efficiency (>14 %), outperforming all furan-based acceptors reported to date and all indacenodithiophene-based acceptors. Our findings show the possibility of photostable furan-based alternatives to the currently omnipresent thiophene-based photovoltaic materials.     

Blocked Phosphates as Photolatent Catalysts for Dynamic Photopolymer Networks

While latent catalysts are a well-established strategy for initiating and controlling the rate of polymerization reactions, their use in dynamic polymer networks is still in its infancy. The ideal latent catalyst should be thermally stable and release a highly active species in response to an external trigger. Here, we have synthesized a temperature resistant (>200 °C) organic phosphate with a photolabile o-nitrobenzyl protecting group that can be cleaved by UV light. Introduced in a visible light curable thiol-click photopolymer, the sequence-dependent λ-orthogonality of the curing and cleavage enables an efficient network formation at 451 nm, without premature release of the catalyst. Once cured, irradiation at 372 nm spatiotemporally activates the phosphate, which catalyzes transesterifications at elevated temperature. The formed catalyst has no effect on the thermal stability of the polymeric network and allows the activation of bond exchange reactions in selected domains of printed 3D objects.     

By how many tautomerisation routes the Watson–Crick-like A·C* DNA base mispair is linked with the wobble mismatches? A QM/QTAIM vision from a biological point of view

Here for the first time we present four novel routes of the tautomerisation via the sequential DPT that links biologically important A·C*(WC) DNA base mispair with Watson–Crick (WC) geometry and wobble (w) A*·C*(w), A·C*_O2(w), A*·C*(w ₁) and A·C(w _⊥) mismatches, pursuing the goal of estimation of their contribution into the transition mutations during DNA biosynthesis. These processes occur without opening of the pairs and are accompanied by the substantial changes in their geometry. A detailed analysis of these pathways leads to an identification of the A·C*(WC)?A*·C*(w) tautomerisation route as the most suitable among these processes from the point of view of the spontaneous point mutagenesis, since it proceeds via the time that is significantly less than the time used by the replicative DNA-polymerase for the incorporation of one incoming nucleotide into the synthesised DNA double helix. This non-dissociative transition occurs through the planar, highly stable, zwitterionic \( {\text{TS}}_{{{\text{A}} \cdot {\text{C*(WC)}} \leftrightarrow {\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} (w )}}^{{{\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} }} \) transition state and dynamically unstable intermediate A⁺·C^?(w) ion pair and is accompanied by the consistent rearrangement of the 10 unique patterns of the specific intermolecular interactions, among which there are from 2 to 4 AH···B H-bonds and 2 loosened A–H–B covalent bridges. Basic physico-chemical properties of this mutual tautomeric transformation, which is internally inherent to the A·C*(WC) and A*·C*(w) base mispairs, are documented, and its possible biological assignment is discussed here.