Electron-Rich EDOT Linkers in Tetracationic bis-Triarylborane Chromophores: Influence on Water Stability,Biomacromolecule Sensing,and Photoinduced Cytotoxicity

Three novel tetracationic bis-triarylboranes with 3,4-ethylenedioxythiophene (EDOT) linkers, and their neutral precursors, showed significant red-shifted absorption and emission compared to their thiophene-containing analogues, with one of the EDOT-derivatives emitting in the NIR region. Only the EDOT-linked trixylylborane tetracation was stable in aqueous solution, indicating that direct attachment of a thiophene or even 3-methylthiophene to the boron atom is insufficient to provide hydrolytic stability in aqueous solution. Further comparative analysis of the EDOT-linked trixylylborane tetracation and its bis-thiophene analogue revealed efficient photo-induced singlet oxygen production, with the consequent biological implications. Thus, both analogues bind strongly to ds-DNA and BSA, very efficiently enter living human cells, accumulate in several different cytoplasmic organelles with no toxic effect but, under intense visible light irradiation, they exhibit almost instantaneous and very strong cytotoxic effects, presumably attributed to singlet oxygen production. Thus, both compounds are intriguing theranostic agents, whose intracellular and probably intra-tissue location can be monitored by strong fluorescence, allowing switching on of the strong bioactivity by well-focused visible light.     

Substituent effects on the photophysical properties of 2,9-substituted phenanthroline copper(I) complexes: a theoretical investigation

The electronic and nuclear structures of a series of [Cu(2,9-(X)₂-phen)₂]⁺ copper(I) complexes (phen=1,10-phenanthroline; X=H, F, Cl, Br, I, Me, CN) in their ground and excited states are investigated by means of density functional theory (DFT) and time-dependent (TD-DFT) methods. Subsequent Born-Oppenheimer molecular dynamics is used for exploring the T₁ potential energy surface (PES). The T₁ and S₁ energy profiles, which connect the degenerate minima induced by ligand flattening and Cu−N bond symmetry breaking when exciting the molecule are calculated as well as transition state (TS) structures and related energy barriers. Three nuclear motions drive the photophysics, namely the coordination sphere asymmetric breathing, the well-documented pseudo Jahn-Teller (PJT) distortion and the bending of the phen ligands. This theoretical study reveals the limit of the static picture based on potential energy surfaces minima and transition states for interpreting the luminescent and TADF properties of this class of molecules. Whereas minor asymmetric Cu−N bonds breathing accompanies the metal-to-ligand-charge-transfer re-localization over one or the other phen ligand, the three nuclear movements participate to the flattening of the electronically excited complexes. This leads to negligible energy barriers whatever the ligand X for the first process and significant ligand dependent energy barriers for the formation of the flattened conformers. Born-Oppenheimer (BO) dynamics simulation of the structural evolution on the T₁ PES over 11 ps at 300 K confirms the fast backwards and forwards motion of the phenanthroline within 200–300 fs period and corroborates the presence of metastable C₂ structures.     

Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100–400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol’s mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.     

Unexpected Efficiency of a Luminescent Samarium(III) Complex for Combined Visible and Near‐Infrared Biphotonic Microscopy

An original samarium(III) complex based on a triazacyclononane platform functionalized with a charge‐transfer antenna chromophore exhibited optimized brightness and was successfully used as an emissive species for two‐photon microscopy experiments in both the visible and near‐infrared spectral ranges.     

The Conformation of a Peptidyl Methyl Ketone Inhibitor Bound to the Human Cytomegalovirus Protease

A weak inhibitor means faster exchange! Since the methyl ketone MK2 is a weak noncovalent peptidyl inhibitor of the human cytomegalovirus protease, exchange between the free and enzyme-bound forms is rapid. This allows for the use of transferred NOE NMR methods and molecular modeling, which show that the bound conformation of MK2 is an extended peptide. This is confirmed by the results of an X-ray crystallographic analysis of a related enzyme–inhibitor complex.     

Applying the hydrodistillation process to Pentadiplandra brazzeana Baill. root: a chemical assessment

A chemical study of the volatile components obtained by applying the hydrodistillation and reflux processes to Pentadiplandra brazzeana roots was performed by GC-FID and GC-MS. The hydrodistillation process showed a total yield of 0.97% with 0.11% of essential oil and 0.86% of volatile compounds from the aqueous reaction medium; in the reflux process, the volatile extract yield was 1.03%. Benzylic-type isothiocyanates were the major degradation products of glucosinolates in the essential oil (95.0%); the CH₂Cl₂ extracts obtained from the aqueous solutions were characterised by alcohols and amines in both processes. This study has shown that during hydrodistillation, only 10% of the glucosinolate degradation products are recovered in the essential oil whereas 90% remain in the aqueous medium, being converted into alcohols and amines. The relative percentages of the different chemical classes recovered in our experimental conditions are discussed in relation with the glucosinolate composition in the raw material.     

Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N¹-([¹¹C]-methyl)-2-bromo-LSD ([¹¹C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [¹¹C]-MBL specific binding was to serotonin 5-HT_2A receptors. However, interactions at serotonin 5HT_1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT_2A/2C agonist N-(2[¹¹CH₃O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([¹¹C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([¹⁵O]-water) or metabolism ([¹⁸F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.     

Benzothiadiazole-Substituted Aza-BODIPY Dyes: Two-Photon Absorption Enhancement for Improved Optical Limiting Performances in the Short-Wave IR Range

Aza-boron dipyrromethenes (aza-BODIPYs) presenting a benzothiadiazole substitution on upper positions are described. The strong electron-withdrawing effect of the benzothiadiazole moiety permits enhancement of the accepting strength and improves the delocalization of the aza-BODIPY core to attain a significant degree of electronic communication between the lower donating groups and the upper accepting groups. The nature of the intramolecular charge transfer is studied both experimentally and theoretically. Linear spectroscopy highlighted the strongly redshifted absorption and emission of the synthesized molecules with recorded fluorescence spectra over 1000 nm. Nonlinear optical properties were also investigated. Strong enhancement of the two-photon absorption of the substituted dyes compared with the unsubstituted one (up to 4520 GM at 1300 nm) results in an approximately 15–20 % improvement of the optical power limiting performances. These dyes are therefore a good starting point for further improvement of optical power limiting in the short-wave IR range.