Unimolecular net heterolysis of symmetric and homopolar σ-bonds.

The unimolecular heterolysis of covalent σ-bonds is integral to many chemical transformations, including SN1-, E1- and 1,2-migration reactions. To a first approximation, the unequal redistribution of electron density during bond heterolysis is governed by the difference in polarity of the two departing bonding partners1-3. This means that if a σ-bond consists of two identical groups (that is, symmetric σ-bonds), its unimolecular fission from the S0, S1, or T1 states only occurs homolytically after thermal or photochemical activation1-7. To force symmetric σ-bonds into heterolytic manifolds, co-activation by bimolecular noncovalent interactions is necessary4. These tactics are only applicable to σ-bond constituents susceptible to such polarizing effects, and often suffer from inefficient chemoselectivity in polyfunctional molecules. Here we report the net heterolysis of symmetric and homopolar σ-bonds (that is, those with similar electronegativity and equal leaving group ability3) by means of stimulated doublet-doublet electron transfer (SDET). As exemplified by Se-Se and C-Se σ-bonds, symmetric and homopolar bonds initially undergo thermal homolysis, followed by photochemically SDET, eventually leading to net heterolysis. Two key factors make this process feasible and synthetically valuable: (1) photoexcitation probably occurs in only one of the incipient radical pair members, thus leading to coincidental symmetry breaking8 and consequently net heterolysis even of symmetric σ-bonds. (2) If non-identical radicals are formed, each radical may be excited at different wavelengths, thus rendering the net heterolysis highly chemospecific and orthogonal to conventional heterolyses. This feature is demonstrated in a series of atypical SN1 reactions, in which selenides show SDET-induced nucleofugalities3 rivalling those of more electronegative halides or diazoniums.

Multiple Triplet Metal-Centered Jahn-Teller Isomers Determine Temperature-Dependent Luminescence Lifetimes in [Ru(bpy)3 ]2.

Understanding the factors that determine the luminescence lifetime of transition metal compounds is key for applications in photocatalysis and photodynamic therapy. Here we show that for [ Ru ( bpy ) 3 ] 2 + ${[{\rm{Ru}}({\rm{bpy}})_{\rm{3}} ]^{{\rm{2 + }}} }$ (bpy = 2,2'-bipyridine), the generally accepted idea that emission lifetimes can be controlled optimizing the energy barrier from the emissive triplet metal-to-ligand charge-transfer (3 MLCT) state to the thermally-activated triplet metal-centered (3 MC) state or the energy gap between both states is a misconception. Further, we demonstrate that considering a single relaxation pathway determined from the minimum that is lowest in energy leads to wrong temperature-dependent emission lifetimes predictions. Instead, we obtain excellent agreement with experimental temperature-dependent lifetimes when an extended kinetic model that includes all the pathways related to multiple Jahn-Teller isomers and their effective reaction barriers is employed. These concepts are essential to correctly design other luminescent transition metal complexes with tailored emission lifetimes based on theoretical predictions.

BitQT: a graph-based approach to the quality threshold clustering of molecular dynamics.

MOTIVATION: Classical Molecular Dynamics (MD) is a standard computational approach to model time-dependent processes at the atomic level. The inherent sparsity of increasingly huge generated trajectories demands clustering algorithms to reduce other post-simulation analysis complexity. The Quality Threshold (QT) variant is an appealing one from the vast number of available clustering methods. It guarantees that all members of a particular cluster will maintain a collective similarity established by a user-defined threshold. Unfortunately, its high computational cost for processing big data limits its application in the molecular simulation field. RESULTS: In this work, we propose a methodological parallel between QT clustering and another well-known algorithm in the field of Graph Theory, the Maximum Clique Problem. Molecular trajectories are represented as graphs whose nodes designate conformations, while unweighted edges indicate mutual similarity between nodes. The use of a binary-encoded RMSD matrix coupled to the exploitation of bitwise operations to extract clusters significantly contributes to reaching a very affordable algorithm compared to the few implementations of QT for MD available in the literature. Our alternative provides results in good agreement with the exact one while strictly preserving the collective similarity of clusters. AVAILABILITY AND IMPLEMENTATION: The source code and documentation of BitQT are free and publicly available on GitHub (https://github.com/LQCT/BitQT.git) and ReadTheDocs (https://bitqt.readthedocs.io/en/latest/), respectively. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Computation of Förster Resonance Energy Transfer in Lipid Bilayer Membranes.

Calculations of Förster Resonance Energy Transfer (FRET) often neglect the influence of different chromophore orientations or changes in the spectral overlap. In this work, we present two computational approaches to estimate the energy transfer rate between chromophores embedded in lipid bilayer membranes. In the first approach, we assess the transition dipole moments and the spectral overlap by means of quantum chemical calculations in implicit solvation, and we investigate the alignment and distance between the chromophores in classical molecular dynamics simulations. In the second, all properties are evaluated integrally with hybrid quantum mechanical/molecular mechanics (QM/MM) calculations. Both approaches come with advantages and drawbacks, and despite the fact that they do not agree quantitatively, they provide complementary insights on the different factors that influence the FRET rate. We hope that these models can be used as a basis to optimize energy transfers in nonisotropic media.

Strong Ligand Stabilization Based on π-Extension in a Series of Ruthenium Terpyridine Water Oxidation Catalysts.

The substitution behavior of the monodentate Cl ligand of a series of ruthenium(II) terpyridine complexes (terpyridine (tpy)=2,2':6',2''-terpyridine) has been investigated. 1 H NMR kinetic experiments of the dissociation of the chloro ligand in D2 O for the complexes [Ru(tpy)(bpy)Cl]Cl (1, bpy=2,2'-bipyridine) and [Ru(tpy)(dppz)Cl]Cl (2, dppz=dipyrido[3,2-a:2',3'-c]phenazine) as well as the binuclear complex [Ru(bpy)2 (tpphz)Ru(tpy)Cl]Cl3 (3 b, tpphz=tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) were conducted, showing increased stability of the chloride ligand for compounds 2 and 3 due to the extended π-system. Compounds 1-5 (4=[Ru(tbbpy)2 (tpphz)Ru(tpy)Cl](PF6 )3 , 5=[Ru(bpy)2 (tpphz)Ru(tpy)(C3 H8 OS)/(H2 O)](PF6 )3 , tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine) are tested for their ability to run water oxidation catalysis (WOC) using cerium(IV) as sacrificial oxidant. The WOC experiments suggest that the stability of monodentate (chloride) ligand strongly correlates to catalytic performance, which follows the trend 1>2>5≥3>4. This is also substantiated by quantum chemical calculations, which indicate a stronger binding for the chloride ligand based on the extended π-systems in compounds 2 and 3. Additionally, a theoretical model of the mechanism of the oxygen evolution of compounds 1 and 2 is presented; this suggests no differences in the elementary steps of the catalytic cycle within the bpy to the dppz complex, thus suggesting that differences in the catalytic performance are indeed based on ligand stability. Due to the presence of a photosensitizer and a catalytic unit, binuclear complexes 3 and 4 were tested for photocatalytic water oxidation. The bridging ligand architecture, however, inhibits the effective electron-transfer cascade that would allow photocatalysis to run efficiently. The findings of this study can elucidate critical factors in catalyst design.

Diastereoselective Synthesis of Steroid-[60]Fullerene Hybrids and Theoretical Underpinning.

The reaction of C60 with pregnen-20-carboxaldehyde, a biologically active synthetic steroid, by using a 1,3-dipolar cycloaddition reaction (Prato's protocol) results in the formation of pyrrolidine rings bearing a new stereogenic center on the C2 of the five-membered ring. The formation of the fullerene-steroid hybrids proceeds with preference for the Re face of the 1,3-dipole, with formation of a diastereomeric mixture in 73:15 ratio. The investigation of the chiroptical properties of these conjugates allowed determining the absolute configuration of the new fulleropyrrolidines. In addition, a thorough spectroscopical study permitted to determine the structure of the two mono-cycloadducts. The electrochemical properties of the new hybrids were also evaluated by cyclic voltammetry, both systems exhibit three quasi-reversible reduction waves which are cathodically shifted in regard to the parent C60. Theoretical calculations help supporting the experimental data. A conformational study combining semiempirical methods and density functional theory has predicted the most stable diastereomer. On the basis of this agreement, a possible reaction mechanism is presented. Additionally, a molecular docking simulation has been carried out using the HIV-1 protease as receptor, thus paving the way to study the possible application of these stereoisomers in biomedicine.

Quality Threshold Clustering of Molecular Dynamics: A Word of Caution.

Clustering Molecular Dynamics trajectories is a common analysis that allows grouping together similar conformations. Several algorithms have been designed and optimized to perform this routine task, and among them, Quality Threshold stands as a very attractive option. This algorithm guarantees that in retrieved clusters no pair of frames will have a similarity value greater than a specified threshold, and hence, a set of strongly correlated frames are obtained for each cluster. In this work, it is shown that various commonly used software implementations are flawed by confusing Quality Threshold with another simplistic well-known clustering algorithm published by Daura et al. (Daura, X.; van Gunsteren, W. F.; Jaun, B.; Mark, A. E.; Gademann, K.; Seebach, D. Peptide Folding: When Simulation Meets Experiment. Angew. Chemie Int. Ed. 1999, 38 (1/2), 236-240). Daura's algorithm does not impose any quality threshold for the frames contained in retrieved clusters, bringing unrelated structural configurations altogether. The advantages of using Quality Threshold whenever possible to explore Molecular Dynamic trajectories is exemplified. An in-house implementation of the original Quality Threshold algorithm has been developed in order to illustrate our comments, and its code is freely available for further use by the scientific community.

BitClust: Fast Geometrical Clustering of Long Molecular Dynamics Simulations.

The growing computational capacity allows the investigation of large biomolecular systems by increasingly extensive molecular dynamics simulations. The resulting huge trajectories demand efficient partition methods to discern relevant structural dissimilarity. Clustering algorithms are available to address this task, but their implementations still need to be improved to gain in computational speed and to reduce the consumption of random access memory. We propose the BitClust code which, based on a combination of Python and C programming languages, performs fast structural clustering of long molecular trajectories. BitClust takes advantage of bitwise operations applied to a bit-encoded pairwise similarity matrix. Our approach allowed us to process a half-million frame trajectory in 6 h using less than 35 GB, a task that is not affordable with any of the similar alternatives.

Alignment and photooxidation dynamics of a perylene diimide chromophore in lipid bilayers.

We present a method of enabling photochemical reactions in water by using biomimetic, water-soluble liposomes and a specifically functionalized perylene diimide chromophore. Linking two flexible saturated C4-alkyl chains with terminal positively charged trimethylammonium groups to the rigid perylene diimide core yielded [1]2+ allowing for its co-assembly at the lipid bilayer interface of DOPG liposomes (DOPG = 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) with a preferred orientation and in close proximity to the water interface. According to molecular dynamics simulations the chromophore aligns preferably parallel to the membrane surface which is supported by confocal microscopy. Irradiation experiments with visible light and in the presence of a negatively charged, water-soluble oxidant were slower in the DOPG-membrane than under acetonitrile-water reaction conditions. The generated radical species was characterized by EPR spectroscopy in an acetonitrile-water mixture and associated to the DOPG-membrane. Time-resolved emission studies revealed a static quenching process for the initial electron transfer from photoexcited [1]2+ to the water soluble oxidant. The findings presented in this study yield design principles for the functionalization of lipid bilayer membranes which will be relevant for the molecular engineering of artificial cellular organelles and nano-reactors based on biomimetic vesicles and membranes.

Activation by oxidation and ligand exchange in a molecular manganese vanadium oxide water oxidation catalyst.

Despite their technological importance for water splitting, the reaction mechanisms of most water oxidation catalysts (WOCs) are poorly understood. This paper combines theoretical and experimental methods to reveal mechanistic insights into the reactivity of the highly active molecular manganese vanadium oxide WOC [Mn4V4O17(OAc)3]3- in aqueous acetonitrile solutions. Using density functional theory together with electrochemistry and IR-spectroscopy, we propose a sequential three-step activation mechanism including a one-electron oxidation of the catalyst from [Mn2 3+Mn2 4+] to [Mn3+Mn3 4+], acetate-to-water ligand exchange, and a second one-electron oxidation from [Mn3+Mn3 4+] to [Mn4 4+]. Analysis of several plausible ligand exchange pathways shows that nucleophilic attack of water molecules along the Jahn-Teller axis of the Mn3+ centers leads to significantly lower activation barriers compared with attack at Mn4+ centers. Deprotonation of one water ligand by the leaving acetate group leads to the formation of the activated species [Mn4V4O17(OAc)2(H2O)(OH)]- featuring one H2O and one OH ligand. Redox potentials based on the computed intermediates are in excellent agreement with electrochemical measurements at various solvent compositions. This intricate interplay between redox chemistry and ligand exchange controls the formation of the catalytically active species. These results provide key reactivity information essential to further study bio-inspired molecular WOCs and solid-state manganese oxide catalysts.

Conceptual DFT analysis of the regioselectivity of 1,3-dipolar cycloadditions: nitrones as a case of study.

The regioselectivity of the 1,3-dipolar cycloaddition of a model nitrone with a set of dipolarophiles, presenting diverse electronic effects, is analyzed using conceptual density functional theory (DFT) methods. We deviate from standard approaches based on frontier molecular orbitals and formulations of the local hard/soft acid/base principle and use instead the dual descriptor. A detailed analysis is carried out to determine the influence of the way to calculate the dual descriptor, the computational procedure, basis set and choice of method to condensate the values of this descriptor. We show that the qualitative regioselectivity predictions depend on the choice of "computational conditions", something that indicates the danger of using black-box computational set-ups in conceptual DFT studies.