Dianionic and Neutral Diboron-Centered Classical Diradicaloids.

Herein, we report the syntheses and electronic structures of crystalline dianionic as well as neutral diboron-centered classical diradicaloids as boron analogues of classical Thiele, Chichibabin, and Müller (this only for dianionic diradicaloids!) hydrocarbons. These are based on borane radical anion and NHC-stabilized boryl radical spin carriers, respectively. All these dianionic diboron-centered diradicaloids exhibit triplet population at room temperature regardless of the π-conjugated spacer: p-phenylene, p,p'-biphenylene, or p,p″-terphenylene. In the case of neutral diboron-centered diradicaloids, the employed π-conjugated spacer plays a crucial role for the triplet population at room temperature: EPR inactive for p-phenylene vs EPR active for p,p'-biphenylene. The findings emphasize the importance of the spin carriers for the resulting ground-state: borane radical anion vs NHC-stabilized boryl radical along with the pivotal role of the π-conjugated spacer as spin-coupler between two spins. Notably, 100 years (a century) after the first report by Krause of the triphenyl borane radical-anion, being isoelectronic to the triphenylmethyl radical, we convey borane radical anion-based diradicaloids. Furthermore, while donor-stabilized boryl radicals were introduced in the 1980s by Giles and Roberts, said concept is herewith being extended to NHC-stabilized boryl radical-based diradicaloids.

Dynamics and Coordination of a P2N2 Ligand - from Twisted Conformation to Chelation.

Based on their general spacial flexibility, their Lewis and Brønsted basicity, and ability to mimic second sphere effects the 1,5-diaza-3,7-diphosphacyclooctane ligand family and their complexes have regained substantial scientific interest. It was now possible to structurally analyze a recently reported member of this family with p-tolyl and t-butyl substituents on P and N, respectively, (P2 p-tolN2 tBu). Notably, the ligand crystallizes with a 'twisted' backbone. This compound is the very first of its kind to have been unambiguously characterized with regard to its chemical and molecular structure as being in this conformation. A temperature-dependent NMR study provides insight into the molecular dynamics of two isomers in solution, which are most likely also both twisted, as judged by the observed limited reactivity. Despite the in principle unfavorable conformation of the free ligand, it was successfully chelated to tungsten and molybdenum centers in mononuclear carbonyl complexes. The ligand, a derivative thereof and four new complexes were comprehensively characterized and analyzed in comparison. This includes single crystal XRD molecular structures of P2 p-tolN2 tBu and all four complexes. P2 p-tolN2 tBu, regardless of its twisted conformation, is able to coordinate to metal centers given that enough energy (heat) for a conformational change is provided.

Comment on "Disclosing Cyclic(Alkyl)(Amino)Carbenes as a One-Electron Reductant: Synthesis of Acyclic(Amino)(Aryl)Carbene-Based Kekulé Diradicaloids".

This correspondence addresses a misassignment of an EPR spectrum of 2 in a recent publication (Chem. Eur. J. 2022, 28, e202104567) by Dr. Jana and co-workers. The original authors have prepared this correspondence together with Dr. Korth.

Carbodicarbenes and Striking Redox Transitions of their Conjugate Acids: Influence of NHC versus CAAC as Donor Substituents.

Herein, a new type of carbodicarbene (CDC) comprising two different classes of carbenes is reported; NHC and CAAC as donor substituents and compare the molecular structure and coordination to Au(I)Cl to those of NHC-only and CAAC-only analogues. The conjugate acids of these three CDCs exhibit notable redox properties. Their reactions with [NO][SbF6 ] were investigated. The reduction of the conjugate acid of CAAC-only based CDC with KC8 results in the formation of hydrogen abstracted/eliminated products, which proceed through a neutral radical intermediate, detected by EPR spectroscopy. In contrast, the reduction of conjugate acids of NHC-only and NHC/CAAC based CDCs led to intermolecular reductive (reversible) carbon-carbon sigma bond formation. The resulting relatively elongated carbon-carbon sigma bonds were found to be readily oxidized. They were, thus, demonstrated to be potent reducing agents, underlining their potential utility as organic electron donors and n-dopants in organic semiconductor molecules.

Liposomal formulation of model pentathiepin improves solubility and stability toward glutathione while preserving anticancer activity.

The biological properties of pentathiepins have been attracting increased attention in recent years. Experiments have shown a wide range of effects of pentathiepins in vitro, such as induction of apoptosis and alteration of mitochondrial membrane potential in cancer cells, and inhibition of antioxidant enzymes, for example, glutathione peroxidase 1 (GPx1). Biological evaluation is sometimes limited due to low aqueous solubility, high lipophilicity, and poor stability toward thiols, for example, glutathione (GSH). To assess whether liposomes are suitable as drug carriers to overcome these drawbacks, a model pentathiepin was formulated in a liposomal preparation. The success of loading liposomes with pentathiepins was evaluated by using ultraviolet-visible light (UV-Vis) spectroscopy, dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC). Through inclusion into 100-nm-sized 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes, the aqueous solubility of a representative pentathiepin could be increased by several orders of magnitude to ca. 400 µM. The stability of the pentathiepin in the presence of GSH was increased fourfold as determined by UV-Vis spectroscopy. In antiproliferation experiments with two human cancer cell lines, no decrease in potency in the liposomal loaded pentathiepin compared to the free pentathiepin was found. In conclusion, liposomes are a suitable carrier for pentathiepins and improve both solubility and stability in the presence of thiols without compromising anticancer activity.

The Mechanism of Metal-Containing Formate Dehydrogenases Revisited: The Formation of Bicarbonate as Product Intermediate Provides Evidence for an Oxygen Atom Transfer Mechanism.

Mo/W-containing formate dehydrogenases (FDH) catalyzed the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. While in the reaction of formate oxidation, the product is CO2, which exits the active site via a hydrophobic channel; bicarbonate is formed as the first intermediate during the reaction at the active site. Other than what has been previously reported, bicarbonate is formed after an oxygen atom transfer reaction, transferring the oxygen from water to formate and a subsequent proton-coupled electron transfer or hydride transfer reaction involving the sulfido ligand as acceptor.

Synthesis of Seven Indolizine-Derived Pentathiepines: Strong Electronic Structure Response to Nitro Substitution in Position C-9.

Seven new 1,2,3,4,5-pentathiepino[6,7-a]indolizines were synthesized in which the pentathiepine moieties bear an indolizine backbone that is derivatized from C-H to F-, Cl-, Br-, I-, NO2-, and CH3-substitutions, respectively, in a meta position relative to the aza group on the pyridine moiety. Their preparation took place via two common steps: (i) a Sonogashira coupling between (4-substituted) 2-bromo- or 2-chloropyridines and propynyl 3,3-diethylacetal, and (ii) a ring closing reaction mediated by a molybdenum oxo-bistetrasulfido complex and elemental sulfur. The latter simultaneously facilitates the 1,2,3,4,5-pentathiepino chain/ring- and indolizine ring-formations. The fluoro derivative was addressed with 2-bromo-5-aminopyridine as the starting material via a Sandmeyer reaction. The iodo derivative was obtained from 5-bromo-2-alkynylpiridine using a metal-assisted variation of the Finkelstein reaction. The requirement to explore different reaction conditions and the varied respective yields of the final products are discussed. The influence of the distinct substitutions on the pyridine moieties, their electronic structures, and respective chemical properties was investigated through a set of spectroscopic/analytical characterizations. Intriguingly, in all cases, the nitro-substituted derivative exhibited a distinct behavior compared to the six other investigated derivatives, which was also addressed computationally. All seven new pentathiepines were crystallized, and their respective molecular structures were determined using single crystal X-ray diffraction. These structures are compared and discussed as are their respective packing patterns.

Fine-Tuning Redox Properties of Heteroleptic Molybdenum Complexes through Ligand-Ligand-Cooperativity.

Heteroleptic molybdenum complexes bearing 1,5-diaza-3,7-diphosphacyclooctane (P2 N2 ) and non-innocent dithiolene ligands were synthesized and electrochemically characterized. The reduction potentials of the complexes were found to be fine-tuned by a synergistic effect identified by DFT calculations as ligand-ligand cooperativity via non-covalent interactions. This finding is supported by electrochemical studies combined with UV/Vis spectroscopy and temperature-dependent NMR spectroscopy. The observed behavior is reminiscent of enzymatic redox modulation using second ligand sphere effects.

Bis-Olefin Based Crystalline Schlenk Hydrocarbon Diradicals with a Triplet Ground State.

A modular approach for the synthesis of isolable crystalline Schlenk hydrocarbon diradicals from m-phenylene bridged electron-rich bis-triazaalkenes as synthons is reported. EPR spectroscopy confirms their diradical nature and triplet electronic structure by revealing a half-field signal. A computational analysis confirms the triplet state to be the ground state. As a proof-of-principle for the modular methodology, the 4,6-dimethyl-m-phenylene was further utilized as a coupling unit between two alkene motifs. The steric conjunction of the 4,6-dimethyl groups substantially twists the substituents at the nonbonding electron bearing centers relative to the central coupling m-phenylene motif. As a result, the spin delocalization is decreased and the exchange coupling between the two unpaired spins, hence, significantly reduced. Notably, 108 years after Schlenk's m-phenylene-bis(diphenylmethyl) synthesis as a diradical, for the first time we were able to isolate its derivative with the same spacer, i.e. m-phenylene, between two radical centers in a crystalline form.

Disclosing Cyclic(Alkyl)(Amino)Carbenes as One-Electron Reductants: Synthesis of Acyclic(Amino)(Aryl)Carbene-Based Kekulé Diradicaloids.

Herein, we disclose cyclic(alkyl)(amino)carbenes (CAACs) to be one-electron reductants under the formation of a transient radical cation as indicated by EPR spectroscopy. The disclosed CAAC reducing reactivity was used to synthesize acyclic(amino)(aryl)carbene-based Thiele and Chichibabin hydrocarbons, a new class of Kekulé diradicaloids. The results demonstrate CAACs to be potent organic reductants. Notably, the acyclic(amino)(aryl)carbene-based Chichibabin's hydrocarbon shows an appreciable population of the triplet state at room temperature, as evidenced by both variable-temperature NMR and EPR spectroscopy.

Heteroatom-Assisted Regio- and Stereoselective Palladium-Catalyzed Carboxylation of 9-Allyl Adenine.

Strategy for the synthesis of acyclic nucleoside analogs of biological relevance via highly regio- and stereoselective C-H functionalization employing heteroatom-assisted palladium-catalyzed carboxylation of 9-allyl adenine is disclosed. Substrate scope with different carboxylic acids was performed giving decent to good yields of the desired products. The method also allowed for the synthesis of deuterated analogs.

Synthesis, characterization, antioxidant, antileishmanial, anticancer, DNA and theoretical SARS-CoV-2 interaction studies of copper(II) carboxylate complexes.

Copper(II) carboxylate complexes [Cu2(OOCR)4L2] (1) and [Cu2(OOCR`)4OCO(R`)CuL2]n (2), where L = 2-methyl pyridine, R = 2-chlorophenyl acetate and R` = 2-fluorophenyl acetate were synthesized and characterized by FT-IR spectroscopy and single crystal X-ray analysis. Complex 1 exhibits the typical paddlewheel array of a dinuclear copper(II) complex with carboxylate ligands. In complex 2, this scaffold is further extended into a polymeric arrangement based on alternate paddlewheel and square planar moieties with distinct coordination spheres. The complexes showed better 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activities and have been found to be more potent antileishmanial agents than their corresponding free ligand acid species. UV-Vis absorption titrations revealed good DNA binding abilities {Kb = 9.8 × 104 M-1 (1) and 9.9 × 104 M-1 (2)} implying partial intercalation of the complexes into DNA base pairs along with groove binding. The complexes displayed in vitro cytotoxic activity against malignant glioma U-87 (MG U87) cell lines. Computational docking studies further support complex-DNA binding by intercalation. Molecular docking investigations revealed probable interactions of the complexes with spike protein, the nucleocapsid protein of SARS-CoV-2 and with the angiotensin converting enzyme of human cells.

Inspired by Nature-Functional Analogues of Molybdenum and Tungsten-Dependent Oxidoreductases.

Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build functional active site analogues. These studies not only led to an ever more detailed mechanistic understanding of the biological template, but also paved the way to atypical selectivity and activity, such as catalytic hydrogen evolution. This review is aimed at representing the last decade's progress in the research of and with molybdenum and tungsten functional model compounds. The portrayed systems, organized according to their ability to facilitate typical and artificial enzyme reactions, comprise complexes with non-innocent dithiolene ligands, resembling molybdopterin, as well as entirely non-natural nitrogen, oxygen, and/or sulfur bearing chelating donor ligands. All model compounds receive individual attention, highlighting the specific novelty that each provides for our understanding of the enzymatic mechanisms, such as oxygen atom transfer and proton-coupled electron transfer, or that each presents for exploiting new and useful catalytic capability. Overall, a shift in the application of these model compounds towards uncommon reactions is noted, the latter are comprehensively discussed.

Realizing 1,1-Dehydration of Secondary Alcohols to Carbenes: Pyrrolidin-2-ols as a Source of Cyclic (Alkyl)(Amino)Carbenes.

Herein we report secondary pyrrolidin-2-ols as a source of cyclic (alkyl)(amino)carbenes (CAAC) for the synthesis of CAAC-CuI -complexes and cyclic thiones when reacted with CuI -salts and elemental sulfur, respectively, under reductive elimination of water from the carbon(IV)-center. This result demonstrates a convenient and facile access to CAAC-based CuI -salts, which are well known catalysts for different organic transformations. It further establishes secondary alcohols to be a viable source of carbenes-realizing after 185 years Dumas' dream who tried to prepare the parent carbene (CH2 ) by 1,1-dehydration of methanol. Addressed is also the reactivity of water towards CAACs, which proceeds through an oxidative addition of the O-H bond to the carbon(II)-center. This emphasizes the ability of carbon-compounds to mimic the reactivity of transition-metal complexes: reversible oxidative addition and reductive elimination of the O-H bond to/from the C(II)/C(IV)-centre.

1,3,5-Triaza-7-phosphaadamantane (PTA) Derived Caged Phosphines for Palladium-Catalyzed Selective Functionalization of Nucleosides and Heteroarenes.

Phosphines have, in combination with transition metals, played a pivotal role in the rapid development of efficient catalytic processes. Caged phosphines constitute a class of three-dimensional scaffolds providing unique control over steric and electronic properties. The versatility of the caged phosphine ligands has been demonstrated elegantly by the groups of Verkade, Gonzalvi as well as Stradiotto. Our research group has also been working extensively for the past several years in the development of 1,3,5-triaza-7-phosphaadamantane-based caged ligands and in this personal note we have summarized these applications pertaining to the modification of biologically useful nucleosides and heteroarenes.

α,α'-Diamino-p-tetrafluoroquinodimethane: Stability of One- and Two-Electron Oxidized Species and Fixation of Molecular Oxygen.

Herein, we report the synthesis, characterization, and reactivity of α,α'-diamino-p-tetrafluoroquinodimethane, a p-tetrafluorophenylene-bridged monosubstituted carbene-based Thiele's hydrocarbon A. The compound exhibits a reversible two-step one-electron oxidation with a marginally stable radical cation state B. The in situ formation of the radical cation could be confirmed by electron paramagnetic resonance spectroscopy. Interestingly, α,α'-diamino-p-tetrafluoroquinodimethane fixates atmospheric oxygen to form a 16-membered peroxide-bridged macrocyclic compound C.

Twisted Push-Pull Alkenes Bearing Geminal Cyclicdiamino and Difluoroaryl Substituents.

The systematic combination of N-heterocyclic olefins (NHOs) with fluoroarenes resulted in twisted push-pull alkenes. These alkenes carry electron-donating cyclicdiamino substituents and two electron-withdrawing fluoroaryl substituents in the geminal positions. The synthetic method can be extended to a variety of substituted push-pull alkenes by varying the NHO as well as the fluoroarenes. Solid-state molecular structures of these molecules reveal a notable elongation of the central C-C bond and a twisted geometry in the alkene motif. Absorption properties were investigated with UV-vis spectroscopy. The redox properties of the twisted push-pull alkenes were probed with electrochemistry as well as UV-vis/NIR and EPR spectroelectrochemistry, while the electronic structures were computationally evaluated and validated.

A computational probe granting insight into intra and inter-stacking interactions in squaraine dye derivatives.

In order to decipher structure function relationships regarding the optoelectronic properties of organic functional materials, two sets of anilinosquaraine dye derivatives were analysed computationally. 2,4-Bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl]squaraine exhibits orthorhombic and monoclinic polymorphs (motif-1 and motif-2) in bulk and spin coated films, respectively, and concomitant J- and H-aggregate spectral features. In the second set, in spite of variation in the n-alkyl chain of the anilinosquaraine derivatives (n-propyl vs. n-butyl; motif-3 and motif-4), both acquired triclinic morphology and intermolecular charge transfer had been identified as the origin of their panchromaticity. The differences between these motifs were closely inspected at the theoretical level including geometrical parameters, internal reorganization energies, charge transfer integrals, drift mobilities, interaction energies and lattice energies along with a comprehensive Hirshfeld surface analysis. A correlation was established between C⋯C type intra-stack interactions with the observed red-shifted absorption patterns in the order motif-1 > motif-3 > motif-4. Hydrophobic interactions, π-π interactions and hydrogen bonds were found to influence the crystal packing patterns and concomitantly the overall molecule planarity and thereby the extent of π-bond delocalization/resonance. Insights into intra-stack and inter-stack interactions based on crystal packing effects are provided, which support and potentially guide the experimentalists' key ideas for shaping and encompassing the applications of promising squaraine derivative materials.

Correction: A computational probe granting insight into intra and inter-stacking interactions in squaraine dye derivatives.

Correction for 'A computational probe granting insight into intra and inter-stacking interactions in squaraine dye derivatives' by Krishna Chaitanya Gunturu et al., Phys. Chem. Chem. Phys., 2021, DOI: .

Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action.

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.