Ligand Complexes Research Articles

Ni(II) and Cu(II) Ion Coordination by the Novel (2E,2′E)-N,N′-(2-Hydroxypropane-1,3-diyl)bis[(2-hydroxyimino)propanamide] Ligand in the Solid State and in Aqueous Medium

In the process of a systematic study of the bis-chelate oxime-amide ligands with different polymethylene spacers and their transition metal complexes, two new Ni(II) and Cu(II) complexes of the mhiea2poh ligand have been isolated, and their molecular and crystal structures determined by single crystal X-ray diffraction. Potentiometric titrations were performed on a range of aqueous solutions in both systems, which allowed the identification of various complex species and afforded their stability constants. ESR spectra of samples with optimised concentrations of complexes in Cu(II)–L–H system were recorded. A distinguishing feature of both systems is the dimerization of anionic pseudo-macrocyclic complexes. The latter is caused either by centrosymmetric hydrogen bonding of the hydroxy group on the propane spacer to the oximato oxygen of the opposing unit or by back-to-back π-stacking of planar complex units. ESR measurements indicated likely coupling of Cu-Cu paramagnetic centres in the dimers.

A fluorescent probe for selective detection of Pd2+ combined with fluorescent composite membranes and bioimaging

Palladium, as a transition metal of the platinum group elements, plays an indispensable role in chemical, pharmaceutical, and industrial production. However, its potential toxicity can pose risks to our health and the environment. In this work, a novel parallel alkyne-amine naphthalene ring fluorescent probe LNA based on Pd2+ coordination has been developed. The basic structure and detection mechanism of the probe have been confirmed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS). The probe LNA has a fluorescence-off response to the Pd2+ with high sensitivity (as fast as 60 s) and excellent selectivity (with a detection limit as low as 0.12 μM). Due to the outstanding fluorescence properties of LNA and the low cytotoxicity of its ligand complexes, it has been successfully applied to carboxymethyl cellulose-based fluorescent composite membranes as well as Pd2+ imaging of living cells.

Metal complexes with selenium-based ligands in organic synthesis

Designing ligands is a crucial and significant element in homogeneous catalysis. Over the past two decades, a range of compounds with selenium substitutions have been employed as scaffolds for ligands in the development of transition metal catalytic systems. Air and moisture stability, good solubility in different solvents, stability toward oxidation and excellent electron-donating properties of selenium atom are some of the key features of organoselenium compounds that make them suitable candidates for application as ligands. The metal complexes of selenium ligands are widely acknowledged for their ability to catalyze diverse organic reactions, including but not limited to the Sonogashira coupling reaction, Heck coupling reaction, Suzuki-Miyaura coupling reaction, imidazole arylation, transfer hydrogenation reaction, oxidation of alcohols, and ortho-arylation of phenols. In certain instances, there has been notable observation of exceptionally high catalytic efficiency. Additionally, catalysis often enables a broad substrate range in numerous scenarios, as it is tolerant towards different functional groups. This review highlights the key synthetic methods employed in the design of recent instances of organoselenium compounds as ligands for synthesizing transition metal complexes. Additionally, it explores their utilization in various preparative organic transformations.<br> The bibliography includes 133 references.

Photo-electrochemical decomplexation of cobalt complexes and enhanced cobalt recovery through electrified membranes

The increasing presence of cobalt-chelated species in semiconductor manufacturing poses significant challenges for wastewater treatment because of their structural stability and high solubility. Efficient decomplexation of these metal–ligand complexes is critical for mitigating heavy metal pollution and enabling resource recovery. This study investigates the (photo)electrochemical decomplexation of cobalt-ethylenediaminetetraacetic acid (Co-EDTA) complexes using a TiO2-encapsulated electrified carbon membrane, with a focus on cobalt recovery. Compared to electrochemical oxidation alone, the photoelectrochemical (PEC) system with 365 nm UV-LED illumination demonstrated better performance, achieving over 90 % EDTA-Na2 removal within 20 min and approximately 50 % Co-EDTA decomposition within 180 min. Kinetic analysis confirmed enhanced reaction rates under PEC conditions, and system robustness was validated across varying applied voltages and electrolyte concentrations, as well as real-world semiconductor wastewater. Mechanistic studies revealed that the PEC process is driven by the generation of hydroxyl radicals (•OH), formed through the interaction of photoinduced electron-hole pairs with surface hydroxyl groups on the TiO2 membrane. These radicals facilitate stepwise decomplexation, breaking down Co-EDTA complexes and releasing cobalt ions. This work highlights the potential of TiO2 electrified membrane-based photo-electrochemical systems for efficient decomplexation and cobalt recovery, offering a sustainable solution for advanced wastewater treatment and resource recovery.

Further transformation of fungal catalyzed transformed metabolite 11β-hydroxy-dianabol into new aromatase inhibitors

Secondary biotransformation of 11β-hydroxy-dianabol (11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one) (1), catalyzed by using two fungi Gibberella fujikuroi and Cunninghamella blakesleeana at ambient conditions, was carried out to synthesize its analogues. Transformation of compound 1 with G. fujikuroi yielded a new metabolite, 11β, 17β-dihydroxy-17α-methyl-5β-androst-1-ene-3-one (2), while four new derivatives, 6β, 17β-dihydroxy-17α-methylandrost-1,4-diene-3,11-dione (3), 15α,17β-dihydroxy-17α-methylandrost-1,4-diene-3,11-dione (4), 6β,11β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), and 7β,11β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6) were obtained by transformation with C. blakesleeana. Compounds 1–6 showed a significant aromatase inhibition with IC50 values in the range of 2.01–3.13 μM as compared to the standard drug, exemestane (IC50 = 0.21 ± 0.16 μM). Aromatase is a valid target for drug discovery against ER+ breast cancers. Compounds 1–6 were subjected to molecular docking studies to predict the key interactions, and the MMGBSA studies to analyze the binding affinity and thermal stability of the protein–ligand complexes. Further, the relationship between the metabolites 1–6 and breast tumor androgen receptors was evaluated by in silico approach to analyze the binding interactions between androgen receptors and metabolites. Moreover, compounds 1–6 were found as non-cytotoxic to BJ (Human fibroblast) normal cell line. Hence, these molecules can be further studied for optimization as potential aromatase inhibitors against breast cancer.

X-ray induced in-situ ferroptosis through the Fenton reaction of iron supplements for the cancer therapy

The potential of iron-based therapeutic agents in enhancing radiotherapy efficacy through catalyzing the Fenton reaction has garnered widespread interest. The inherent instability of ferrous ions requires the use of complex ligands for the ligand-dependent reduction from Fe3+ to Fe2+, thereby boosting ferroptosis through inducing the Fenton reaction. However, the reliance on complex redox systems and potential long-term toxicity have seriously limited the clinical application in cancer treatment. In this study, we propose an innovative approach that utilizes the reduction capabilities of hydrated electrons generated by X-ray to directly reduce both ferric ions (Fe3+) and Iron Proteinsuccinylate, a clinically used iron supplement. Our experiments showed that over 20 % of Fe3+, at a concentration of 23 μM, was reduced by X-ray without the need for ligand involvement. Furthermore, both in vitro and in vivo studies confirmed that Iron Proteinsuccinylate exhibited the highest tumor growth inhibition rate through the Fenton reaction and ferroptosis, offering a new and safer method for the in-situ reduction of Fe3+ and enhancing the efficacy of radiotherapy.

In Silico Molecular Dynamics and 3D‐QSAR Study on Thiazolidinedione Derivatives as Dual Inhibitors of DPP IV and PTP1B (DDPI's) for the Management of T2DM

AbstractSimultaneous inhibition of dipeptidyl peptidase IV and protein tyrosine phosphatase 1B as DDPI's emerged as a therapeutic intervention for the management of T2DM. In the present study, we have employed molecular dynamics simulation in conjugation with the field‐based 3D QSAR studies on a dataset having DDPI activities to identify the spatial fingerprints of target‐specific thiazolidinedione analogs. Separate contours were generated for both DPP IV and PTP1B showing respective pharmacophoric structural requirements for optimal inhibitory activity. These developed 3D QSAR models also showed good statistical measures (DPP IV: r2 = 0.9468; q2 = 0.7173, and PTP1B: r2 = 0.9718; q2 = 0.819) with the excellent predictive ability with PLS‐generated validation constraints. Comparative steric and electrostatic features were elucidated using respective contour maps for selective target‐specific favorable activity. Furthermore, molecular docking was used for elucidating the mode of binding as DDPI's to DPP IV and PTP1B, along with MD simulation (200 ns) analysis such as RMSD, RMSF, Rg, SASA, PCA, and FEL. These studies revealed that all the protein‐ligand docked complexes elicited an overall better stability as compared to reference ligand (vildagliptin or ertiprotafib) complexes. Molecular docking studies revealed that compound 24 (DPP IV: −150.667 kcal/mol; PTP1B: −142.792 kcal/mol) showed maximum affinity toward both the proteins DPP IV and PTP1B, as compared to their respective standard inhibitor, i.e., vildagliptin −99.9843 kcal/mol and ertiprotafib −125.399 kcal/mol, respectively. A comparative study of these developed multitargeted QSAR models along with molecular docking and dynamics study were employed for the optimization of drug candidates as DDPI's. Compound 24 showed most stable behavior in the binding pockets of both the enzymes, as compared to their respective standard inhibitors. This study will be helpful in designing novel DDPIs with appropriately substitute thiazolidinedione for the management of T2DM. The designed compound YSR‐14 exhibited the predicted IC50 values of 0.143 µM in DPP IV and 0.158 µM in PTP1B along with their excellent binding affinity against both targets.

Iron complex with multiple negative charges ligand for ultrahigh stability and high energy density alkaline all-iron flow battery

Alkaline all-iron flow batteries (AIFBs) are highly attractive for large-scale and long-term energy storage due to the abundant availability of raw materials, low cost, inherent safety, and decoupling of capacity and power. However, a stable iron anolyte is still being explored to address complex decomposition, ligand crossover, and energy density to improve battery performance. Herein, a promising metal-organic complex, Fe(NTHPS), consisting of FeCl3 and 3,3',3''-nitrilotris(2-hydroxypropane-1-sulfonate) (NTHPS), is specifically designed for alkaline all-iron flow battery. The NTHPS exhibits strong binding strength with iron ions, resulting in ultrahigh stability during the charge-discharge process. AIFB based on the [Fe(CN)6]4- catholyte and Fe(NTHPS) showcases an exceptionally high capacity retention of 97.8% after 2000 cycles (0.0011% per cycle), maintaining high coulombic efficiency near 100%. Furthermore, with a solubility as high as 1.82 mol L-1, the Fe(NTHPS) anolyte demonstrates an ultra-high theoretical capacity of 47.23 Ah L-1. This multiple negative charges ligand not only resolves existing barrier associated with AIFBs, but also provides valuable insight for their commercial application.

Synthesis, Spectral Characterization, Antimicrobial Activity, DFT Calculations, Molecular Docking and ADME Studies of Novel Schiff Base Co(II), Ni(II), Cu(II) and Zn(II) Complexes Derived from 4-nitro-ortho-phenylenediamine.

A condensation reaction was carried out between 4-nitro-ortho-phenylenediamine and 5-bromosalicyaldehyde to synthesize a novel Schiff base ligand 2,2'-[(1E,1'E)-(4-nitro-1,2-phenylene) bis (azaneylylidene) bis (methaneylylidene)] bis (4-bromophenol) [NB] in the current investigation. This was followed by the synthesis of metallic complexes comprising the Co(II), Ni(II), Cu(II) and Zn(II) transition metal ions. A hexadentate environment encircling metal complexes was corroborated by the results of varied spectroscopic methods that were employed to unravel the structure of the ligand and metal complexes. The Tauc's plot and Urbach energy were utilized for quantifying the optical energy band gap to provide insight into optical characteristics. The Coats-Redfern method of thermal analysis was implemented to do the kinetic and thermodynamic calculations. Furthermore, DFT studies were performed to predict geometrical structures and the stability of the compounds. Thorough investigation to evaluate their biological efficacies, docking studies was executed against COVID-19 main protease (PDB-7VAH), Dengue virus NS2B/NS3 protease (PDB-2FOM) and Mycobacterium Tuberculosis (PDB-5AF3). Apart from this, in silico ADMET studies were also accomplished for elucidation of drug likeness characteristics and the results attained disclose the significant proficiency of synthesized compounds. Besides this, antimicrobial studies were assessed with different microbial strains and result validates cobalt and zinc complexes as most potent against the selected bacterial and fungal strains.

Synthesis, characterization, X-ray structure, and DFT calculations of Zn complex encompassing HLN2O ligand: Relevance in cytotoxicity and antifungal photodynamic therapy.

This article presents the synthesis, characterization, and X-ray crystallographic features of one new Zn complex derived from a Salen-type tridentate ligand (HLN2O). A single-crystal diffraction study determined the complex crystal structure, which confirms that it crystallizes in the orthorhombic space group P212121. The single-crystal structure is constructed using the unique mononuclear component [ZnLN2°] and supramolecular CH∙∙∙π type interaction, resulting in a 1D structure. The IR, HRMS, and NMR study also support the complex structure. The Zn metal centre has a distorted square pyramidal geometry with τ value of 0.49. The Hirshfeld surfaces and 2D fingerprint confirm predominant H…H (77.9 %) interactions, with minor H…O, H…C, and H…N (5.0 %, 4.9 %, and 0.2 %). DFT calculations employed the B3LYP-D3/Lanl2DZ class of theory. FMO/MEP explains the complex reactivity perspective, while IP (4.71 eV) and low EA (1.11 eV) suit biological applications. The bonding gateway was analysed using NBO/QTAIM-NCI and ELF-LOL plots. Cytotoxicity was assessed using the Trypan blue exclusion method and tested against the DLA cell line, showing effectiveness against the DLA cell and suggesting complex potential as an anticancer agent. Antifungal photodynamic therapy (APDT) explored that ligand and Zn complex have significant activity against C. albicans. Finally, molecular docking simulations substantiate the experimental findings.

Alkynyl Ligands Templated Assemblies of Silver Nanoclusters with Exceptional Electrochemiluminescence Activity for Pancreatic Cancer Specific tsRNAs Measurement.

Proper manipulation of the ligand complex on the motifs of metal nanoclusters (MNCs) to form an ordered self-assembly is an effective approach to enhance the electrochemiluminescence (ECL) emission of MNCs. We report a facile approach for the preparation of self-assembled AgNCs (AgNCsAssy) induced by alkynyl ligands with enhanced ECL and stability. The formation of these AgNCsAssy was simultaneously driven by the diverse coordination modes of alkynyl ligands with Ag and intercluster interactions, for which it was found that the para-substituted alkynyl ligands exhibited apparently irregular nanoparticles, while the monosubstituted counterparts were present in the form of ribbons. The calculations revealed that the energy gap between the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) played a crucial role in their ECL emissions because of the substituent effects, especially, the low-lying LUMO levels could help to enhance the ECL emission. Moreover, mechanistic studies revealed that both the coreactant and alkynyl ligands made significant contributions to the ECL performance. Concurrently, the CRISPR-associated proteins (CRISPR-Cas) 12a system shows great potential in biosensing applications due to the advantages of easy design and precise targeting. As a proof of concept, we integrated the cascade amplification of catalytic hairpin assembly (CHA) circuit and the collateral cleavage activity of CRISPR-Cas12a to construct an ultrasensitive ECL biosensor for pancreatic cancer (PC)-specific tsRNAs, with a detection limit of 3.33 fM. This work is not only instructive for the synthesis of self-assembled MNCs with high ECL activities but also contributes to the understanding of the ECL mechanism of self-assembled MNCs.

Synthesis, characterization, biological activity, and modelling protein docking of divalent, trivalent, and tetravalent metal ion complexes of new azo dye ligand (N,N,O) derived from benzimidazole

The ligand 2-[2′-(benzimidazole)azo]-4,6-dimethyl benzoic acid (BADMB) was employed to create coordination complexes with Pd(II), Co(III), and Pt(IV) ions. A variety of analytical methods were utilized to verify the structures of the synthesized chelates, including microanalysis, 1H NMR, 13C NMR, UV–Vis spectroscopy, FT-IR, mass spectrometry, magnetic susceptibility, molar conductivity, X-ray diffraction (XRD), and thermal analysis. The stoichiometry of the metal complexes was 1:1 [M:L] in the case of both Pd(II) and Pt(IV) complexes while that of the Co(III) complex was 1:2 [M:L]. The results of molar conductivity measurements confirmed that all of the complexes are electrolytes and that they fall within the range 15.74–40.11 Ω−1 cm2 mol−1. The findings indicated that the Co(III) and Pt(IV) complexes adopt an octahedral geometry, with the formulas [Co(BADMB)2]Cl·H2O and [Pt(BADMB)Cl3]·H2O, respectively. In contrast, the Pd(II) complex, represented by the general formula [Pd(BADMB)Cl]·H2O, has a square planar geometry. BADMB acts as a trident (N,N,O) ligand through two nitrogen atoms from the benzimidazole ring and an azo group and one oxygen atom of the carboxyl group. The antimicrobial activity of these compounds was evaluated against a variety of microorganisms, including Streptococcus, Staphylococcus aureus, Penicillium spp., and Aspergillus, as well as multidrug resistance. In addition, all compounds were active against Penicillium spp. fungi compared to the other microorganisms examined. Moreover, the cytotoxic effects of the BADMB, Pd(II), and Pt(IV) complexes were evaluated in a human hepatocellular carcinoma cell line (HepG2) and a normal cell line (WRL68). A molecular docking study was performed using MOE 2015 software and the PDBsum online server. The compounds showed a binding free energy greater than 5 kcal/mol and an RMSD value was present in the range of 1.41 to 2.01 Å, indicating their potential as ligands for further molecular studies with selected targets.

Virtual Screening and Biological Evaluation of Natural Products as Novel VPS34 Inhibitors that Modulate Autophagy.

VPS34 is a sole member of class III phosphoinositide 3-kinase involved in endosomal trafficking and autophagosome formation, making it an interesting target for cancer treatment. Here, we investigated 5,774 natural products using structure-based virtual screening against human VPS34. 10 natural products identified by virtual screening were purchased and tested in VPS34 ADP-Glo assay, yielding several potential VPS34 inhibitors. Amongst, Salvianolic acid A (4) and Ellagic acid (8) inhibited VPS34 with IC50 values of 2.46 and 3.12 uM, respectively, more potent than the positivity control 3-MA. Moreover, in vitro assays demonstrated that both of the compounds suppressed vesicle trafficking in cell-based assay. Significantly, Salvianolic acid (4) effectively prevented autophagy in Hela cells induced either by starvation or Rapamycin, an mTOR inhibitor. In addition, in silico analysis was done to elucidate the binding mechanisms of the ligand in complex with VPS34. Overall, this study highlights the efficacy of structure-based virtual screening and presents several natural products as VPS34 inhibitors that modulate autophagy.

Synthesis of derived Cu(II) complex from Schiff base of Vitamin B6 and antihypertensive hydralazine: DNA interaction, biological application and molecular docking studies

A novel Schiff base ligand (E)-5-(hydroxymethyl)-2-methyl-4-((2-(phthalazin-1-yl)hydrazineylidene)methyl)pyridin-3-ol was synthesized through the condensation of antihypertensive hydralazine and Pyridoxal (Vitamin B6) ligands. This fabricated Schiff base (L) was a precursor for developing a unique Cu(II) complex. TheSchiff base ligand and Cu(II) complex structureswere characterized using various analytical tools, including IR, UV–Vis Spectroscopy and NMR. An octahedron geometry of this complex was proposed for the assigned molecular formula [Cu(L)2].3H2O. The molecular structures of theSchiff base ligand and its Cu(II) complex have been optimized using the B3LYP functional and the 6-311G++(d,p) basis set. Investigating the interaction of this prepared Cu(II) complex with calf thymus DNA (CT-DNA) molecules was operated using UV–Vis spectrophotometry, viscosity measurement, electrochemical studies, gel electrophoresis, and molecular docking. In vitro cytotoxicity was conducted using the MTT assay on four human tumor cell lines including hepatocellular carcinoma, estrogen-dependent breast cancer, melanoma, triple-negative breast cancer as well as healthy human skin fibroblasts.

Exploring potential therapeutic candidates against COVID-19: a molecular docking study

The COVID-19 pandemic, caused by SARS-CoV-2, has made it urgently necessary to develop effective therapeutic options, and in recent years, computational biological tool assisted to achieve this goal. We conducted MD simulations using six SARS-CoV-2 proteins and 31 ligands to identify possible inhibitors as well as evaluate the binding efficiency of them. Post simulation study showed that 6VSB-Dactinomycin complex reveals the most stable binding, protein flexibility, and robust structural integrity, making it a promising model for therapeutic studies. Our study assessed the therapeutic potential of antiviral candidates against covid-19 virus using computational and experimental method, including the flexibility and stability of twelve docked protein–ligand complexes using normal mode analysis (NMA) and molecular dynamics (MD) simulations. After MD simulation, Dactinomycin and Ivermectin showed significant deformability and high binding affinities for Spike protein and RNA-dependent RNA polymerase, respectively. Remarkably, Dactinomycin showed greater binding to the Helicase protein, but Hesperidin and Epigallocatechin gallate (EGCG) exhibited encouraging interactions with the Nucleocapsid protein and Main protease. Analysis of docking experiments and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) showed the toxicity profiles and binding affinity of various drugs with key viral proteins. Toxicity of major drugs exhibited low to moderate although Dactinomycin, Ivermectin and vitamin-D exhibited higher degree of toxicity. Carcinogenicity observed in Quercetin, Baricitinib, Luteolin, Berberine, and Favipiravir while hepatotoxicity was not found in most case. Although EGCG and Hesperidin exhibit potential, more studies are required to evaluate effectiveness against approved drugs such as Remdesivir. This integrated approach shows that an integration of computational predictions with experimental data can help to support the development of antiviral drugs by adding novel perspectives in the safety profiles and efficiency of potential drugs.

Computational and experimental insights into glycyrrhizin-loaded nanostructured lipid carriers: docking, dynamics, design optimization, and anticancer efficacy in lung cancer cells

BackgroundLung cancer (LC) remains a predominant global health concern, especially with escalating tobacco-smoking rates. Present study provides computational screening, molecular dynamics, DFT and simulation analysis of phytoconstituents on EGFR receptors (2ITY and W2O), followed by selection of highest docking score phytoconstituents among 45 for further analysis. The formulation was optimized by Central composite design. Nanostructured-lipid carriers were prepared by high-speed homogenization, combining a 1:1 ratio of liquid lipid (Castor oil) and melted solid lipid (glyceryl monostearate) with 4% surfactant (tween 80) in a water phase containing Glycyrrhizin. The resulting mixture underwent high-speed homogenization at 8000 rpm for 40 min, followed by sonication for 15 min to achieve formulation development of GNLC. The anticancer potential of GNLC have been proved by experimental analysis through MTT assay using A549 Cell lines.ResultsGlycyrrhizin was found to possess maximum docking score − 8.863 and − 8.837 on both 2ITY and W2O respectively. The study unveils Glycyrrhizin’s interactions with EGFR pivotal in cancer progression and treatment. Molecular dynamics simulations highlighted the structural and dynamic interactions within a protein–ligand complex, indicating both stability and flexibility characteristics. DFT analysis of Glycyrrhizin revealed its molecular properties, suggesting stability and potential reactivity. Glycyrrhizin loaded nanostructured lipid carriers (GNLC) have been developed and analysed by various parameters like particle size and drug release zeta potential, SEM analysis, and solubility analysis reveals critical insights into their optimization for effective drug delivery. Both GNLC and Doxorubicin (0.78–50 µg/ml) were used for the activity. The anticancer potential at 12.50, 25 and 50 µg/ml pf GNLC was found to be statistically significant and was comparable with that of standard group Doxorubicin. The observed structural transformations in Glycyrrhizin into a lipid matrix indicate potential enhancements in its drug release.ConclusionsGNLC shows promising anti-cancer potential in lung cancer, further pre-clinical and clinical studies, is crucial to validate its efficacy, safety, and integration into standard therapeutic regimens.Graphical abstract

Zwitterionic 2-Phosphaethene-thiolates [(LC)P=CS(LC/P)]+ as PCS Building Blocks (LC=NHC, LP=PR3).

The zwitterionic compounds [(LC)P=CS(LC/P)]+ (3+, LC=NHC, LP=PR3), featuring cationic substituents at the phosphorus and carbon atoms, are synthesized as their triflate salts at a multi-gram scale from the reaction of Lewis base adducts of CS2, namely LC/P-CS2 (4), with a combination of [(LCP)4][OTf]4 (1[OTf]4) and Ph3P. The feasibility of using 3+ as PCS building blocks is showcased in their reactions with representative electrophiles (MeOTf) and nucleophiles (MesMgBr, Ph3PCH2), leading to selective functionalization of the PCS core at the S- and P-terminus, respectively. Additionally, it is reported that 3+ can function as ambident nucleophiles with AgOTf (2 equivalents), affording unprecedented linear coordination polymer [Ag2(OTf)3-μ2:κP,κS-((LC)P=CS(PCy3))]+ (6 b), where the PCS moiety acts as a bridging ligand in transition metal complexes for the first time. Reduction of 3+ facilitates the cleavage of the P- and C-bound substituents leading to the formation of the [PCS]- anion. Moreover, cycloaddition reactions of 3+ with 1[OTf]4 are shown to selectively yield five- and eight-membered polyphosphorus heterocycles. Preliminary results suggest the possibility of activating the C-S bond in [(LC)P=CS(LC)]+, resulting in the formation of [(LC)P=C(LC)-P(LC)][OTf]2, 12[OTf]2, which may serve as a synthon for the PCP unit in future studies.

Zwitterionic 2‐Phosphaethene‐thiolates [(LC)P=CS(LC/P)]+ as PCS Building Blocks (LC = NHC, LP = PR3)

The zwitterionic compounds [(LC)P=CS(LC/P)]+ (3+, LC = NHC, LP = PR3), featuring cationic substituents at the phosphorus and carbon atoms, are synthesized as their triflate salts at a multi‐gram scale from the reaction of Lewis base adducts of CS2, namely LC/P–CS2 (4), with a combination of [(LCP)4][OTf]4 (1[OTf]4) and Ph3P. The feasibility of using 3+ as PCS building blocks is showcased in their reactions with representative electrophiles (MeOTf) and nucleophiles (MesMgBr, Ph3PCH2), leading to selective functionalization of the PCS core at the S‐ and P‐terminus, respectively. Additionally, it is reported that 3+ can function as ambident nucleophiles with AgOTf (2 equivalents), affording unprecedented linear coordination polymer [Ag2(OTf)3‐μ2:κP,κS–((LC)P=CS(PCy3))]+ (6b), where the PCS moiety acts as a bridging ligand in transition metal complexes for the first time. Reduction of 3+ facilitates the cleavage of the P‐ and C‐bound substituents leading to the formation of the [PCS]– anion. Moreover, cycloaddition reactions of 3+ with 1[OTf]4 are shown to selectively yield five‐ and eight‐membered polyphosphorus heterocycles. Preliminary results suggest the possibility of activating the C–S bond in [(LC)P=CS(LC)]+, resulting in the formation of [(LC)P=C(LC)–P(LC)][OTf]2, 12[OTf]2, which may serve as a synthon for the PCP unit in future studies.

Formally Zerovalent Bis(arene) Germylene Complexes of Zirconium and Hafnium.

Tetrachlorides of zirconium- and hafnium form adducts (2,3) with an intramolecular germylene phosphine Lewis pair. Two electron reduction treating the adducts with [MesNacnacMg]2 gives the low valent metal complexes (4, 5) featuring η6-Trip coordination at the Zr(II) and Hf(II) metal atom. Reduction of the M(II)-complexes gives the zerovalent metal complexes of zirconium (6) and hafnium (7), which have been structurally characterized. Two arene moieties and the germylene exhibit metal coordination. Puckered coordination of a P-phenyl unit was observed for both derivatives 6 and 7. Four electron reduction of a reaction mixture of metal tetrachloride with the germylene-phosphine Lewis pair also gives the zerovalent complexes in good yield. Carbonyl complexes were synthesized treating the reduced metal complexes with carbon monoxide. Dimethylbutadiene shows a reaction with an arene moiety and the coordinated germylene ligand of the zerovalent complexes. A cyclohexadienyl and a triorganogermate ligand are formed. For zirconium this reaction is reversible at room temperature.

GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models of physiological ligand complexes.

G protein-coupled receptors (GPCRs) are membrane-spanning transducers mediating the actions of numerous physiological ligands and drugs. The GPCR databaseGPCRdb supports a large global research community with reference data, analysis, visualization, experiment design and dissemination. Here, we describe our sixth major GPCRdb release starting with an overview of all resources for receptors and ligands. As a major addition, all ∼400 human odorant receptors and their orthologs in major model organisms can now be studied across the various data and tool resources. For the first time, a Data mapper page enables users to map their own data onto receptors visualized as a GPCRome wheel, tree, clusters, list or heatmap. The structure model data have been expanded with models of physiological ligand complexes and updated with new state-specific structure models of all human GPCRs (built using AlphaFold, RoseTTAFold and AlphaFold-Multistate). Furthermore, a structure or model (pdb file) can now be queried against GPCRdb's entire structure/model collection through a Structuresimilarity search page implementing FoldSeek. Finally, for ligands, new search tools can query names, database identifiers, similarities or substructures against integrated entries from the ChEMBL, Guide to Pharmacology, PDSP Ki, PubChem, DrugCentral and DrugBank databases. GPCRdb is available at https://gpcrdb.org.