Oxygen-Dependent Light-Induced Lipid Membrane Perturbation by TLD1433 as a Potential Contributor to Phototoxicity

Abstract. TLD1433 (Ruvidar®) is a Ru(II) polypyridyl complex currently in phase II clinical trials for the treatment of non-muscle invasive bladder cancer

doi.org

uv.es

Synthetic Mechanism of a Fe(II) N-Heterocyclic Carbene Bidentate Complex Revealed by Electronic Structure Methods

Octahedral Fe(II) complexes with bidentate N-heterocyclic (NHC) ligands are solid candidates for photoactive materials based on first-row transition metals. Despite the remarkable advances in ligand d...

doi.org

Intercalation Favors DNA Covalent Photobinding in Photoresponsive Dual PDT/PCT Bimetallic Assemblies

The local treatment of solid tumors through photoactivated therapies demands the development of alternative strategies independent of oxygen levels, which are often very low in cancerous tissues. In this regard, the combination of an efficient reactive oxygen species (ROS) photogenerator with a drug that covalently targets DNA represents a valuable approach due to the in situ combination of type I/II photodynamic reactions with the covalent blockage of the DNA biological function. In this context, the theoretical framework of the chemical events that cause the observed phototoxicity is far from being fully understood, especially the dynamic factors, timescales, and environmental effects. This work sheds light on the molecular basis of these events by studying the DNA photoreactivity of a Ru(II)/Os(II) and a Pt(II) bimetallic assembly via microsecond molecular dynamics and multiscale biased quantum mechanics/molecular mechanics (QM/MM) MD simulations. Analysis of the DNA interaction modes reveals persistent major/minor groove interactions of the photosensitizer and a thermodynamically favored DNA intercalation. On the other hand, the free energy landscapes reveal kinetically fast (energy barriers ca. 6 kcal·mol–1) ligand exchange reactions between the N7 position of guanine and the platinum center in the triplet excited state, clearly highlighting the role of light in accelerating the chemical process. Additional analyses suggest that DNA intercalation, often associated with high cellular toxicity, could instead be seen as an opportunity to increase phototoxicity indexes by reducing the DNA conformational space available for photoreactions and improving absorption properties.

doi.org

Predicting Molecular Laser Properties from First-Principles Using Machine Learning-Based Nuclear Ensemble Approach Spectra

The accurate prediction of absorption and emission spectra of molecular compounds using quantum mechanical (QM) methods is essential for understanding and designing laser materials, especially when ex...

doi.org

easyPARM v4.00: A Python-based tool for the automated parameterization of metalloproteins and metal-organic polyhedra with multiple metal centers

Force-field parameters for classical molecular dynamics simulations of metal centers are often derived from electronic structure calculations due to the inexist

doi.org

π-Extended Ru–COUBPY Photosensitizers for In Vivo Anticancer Phototherapy Using One-Photon 780 nm Near-Infrared Light

Photodynamic therapy (PDT) is a promising cancer treatment modality, offering precise spatial and temporal control of drug activation using light. However, clinical translation of current photosensiti...

doi.org

Low-load Θ-metallacarboranes as safe and efficient photoredox catalysts for UVA-driven oxidation in water

Guerrero et al. report two efficient 3d6 and 3d5 metallacarborane photoredox catalysts with identical structures that selectively oxidize alcohols and alkenes in water at low catalyst loadings. UVA irradiation enhances performance despite weak absorption, demonstrating that earth-abundant metals can rival precious metal catalysts in photoredox applications.

cell.com

Openings

huixrotllant.github.io

Achieving red-light anticancer photodynamic therapy under hypoxia using Ir(III)-COUPY conjugates

Despite the potential of photodynamic therapy (PDT), this oxygen-dependent oncological treatment is greatly restricted in the clinic by the well-known hypoxic feature of solid tumors. Here we provide ...

doi.org

Geneva Centre for Inflammation Research - UNIGE on LinkedIn: #psoriasis #interleukin #il38 #inflammation #cytokine #researcharticle…

🔬 What if IL-38 could unlock new ways to treat inflammatory diseases like #psoriasis? After the discovery of interleukin (IL)-38 in 2001, early studies…

linkedin.com

easyPARM: Automated, Versatile, and Reliable Force Field Parameters for Metal-Containing Molecules with Unique Labeling of Coordinating Atoms

The dynamics of metal centers are challenging to describe due to the vast variety of ligands, metals, and coordination spheres, hampering the existence of general databases of transferable force field parameters for classical molecular dynamics simulations. Here, we present easyPARM, a Python-based tool that can calculate force field parameters for a wide range of metal complexes from routine frequency calculations with electronic structure methods. The approach is based on a unique labeling strategy, in which each ligand atom that coordinates the metal receives a unique atom type. This design prevents parameter shortage, labeling duplication, and the necessity to post-process output files, even for very complicated coordination spheres, whose parametrization process remain automatic. The program requires the Cartesian Hessian matrix, the geometry xyz file, and the atomic charges to provide reliable force-field parameters extensively benchmarked against density functional theory dynamics in both the gas and condensed phases. The procedure allows the classical description of metal complexes at a low computational cost with an accuracy as good as the quality of the Hessian matrix obtained by quantum chemistry methods. easyPARM v2.00 reads vibrational frequencies and charges in Gaussian (version 09 or 16) or ORCA (version 5 or 6) format and provides refined force-field parameters in Amber format. These can be directly used in Amber and NAMD molecular dynamics engines or converted to other formats. The tool is available free of charge in the GitHub platform (https://github.com/Abdelazim-Abdelgawwad/easyPARM.git).

doi.org

GitHub - Abdelazim-Abdelgawwad/easyPARM: easyPARM is a computational tool developed to simplify the derivation of force field parameters for metal-containing molecular systems and to enable charge res...

easyPARM is a computational tool developed to simplify the derivation of force field parameters for metal-containing molecular systems and to enable charge restraints on specific atoms. - Abdelazim...

github.com