Properties Of Ligands Research Articles

Crystal design, spectroscopic analyses and antibacterial study of new carbazate ligands and their Cu(II) complexes

The current work reports the synthesis and crystal structures of two carbazate ligands, 2-hydroxyacetophenone-methylcarbazate (HL1) and 2-hydroxyacetophenone-benzylcarbazate (HL2), and their Cu(II) complexes [Cu(L1)(CH3OH)]2 (1) and [Cu(L2)]n (2). All compounds were characterized by X-ray single-crystal analysis, spectroscopic and physicochemical methods. Intermolecular interactions were analyzed quantitatively with the 3D Hirshfeld surface and the 2D fingerprint plots. The dimeric complex (1) exhibits a μ2-oxo group located between the two metal ions, an ONO-donor system, and a coordinated methanol molecule with a square-pyramidal geometry to the metal ions. The polymeric complex (2) shows the Cu(II) atom tetracoordinate, bonded to two anionic carbazate, through the ONO-donor system of one molecule, and to a deprotonated nitrogen atom from the second molecule of the ligand. This one-dimensional network shows the metal center with a square planar geometry. The antibacterial properties of the free ligands and metal complexes have been evaluated against periodontopathogenic bacterial strains and were observed to increase the activity after the complexation of the carbazates.

Tuning the phase separation properties of HP1α through ligand interactions.

Heterochromatin protein 1α (HP1α) is a crucial component for gene repression and the structural integrity of heterochromatin. It is proposed that HP1α functions through a liquid-liquid phase separation (LLPS) mechanism where HP1α compacts nucleosome arrays into a liquid compartment and prevents transcription factors from accessing chromatin. HP1α can undergo LLPS via phosphorylation of the N-terminus extension (NTE) or through interactions with DNA/nucleosomes. The multidomain architecture of HP1α allows for simultaneous multivalent interactions with other HP1α proteins and multiple binding partners. These multivalent interactions are believed to be important for forming and maintaining heterochromatin structure but their exact role in HP1α LLPS is not well understood. In our study, we used experimental and computational approaches to investigate how a series of peptides from HP1α binding partners can fine tune the ability of the protein to undergo phase separation. Our results showed that in phosphorylation-driven LLPS, positively charged peptides enhance phase separation, while negatively or near neutral charged peptides disrupt the process. DNA-driven LLPS can also be inhibited by negatively or near neutral charged ligands. However, in this case, positively charged peptides compete with HP1α for DNA interactions, which also disrupts LLPS. Our results suggest that phosphorylation-driven LLPS has a larger tunability range compared to phase separation with DNA, and that the electrostatic properties of HP1α ligands play an important role in modulating this process. Our study provides insights into the potential mechanisms of heterochromatin regulation where binding partners may modulate the biophysical properties of HP1α to control access to chromatin and the genetic information in the cell.

Multi-target molecular dynamic simulations reveal glutathione-S-transferase as the most favorable drug target of knipholone in Plasmodium falciparum

Knipholone is an antiplasmodial phytocompound obtained from the roots of Kniphofia foliosa. Despite several available studies, the molecular drug targets of knipholone in P. falciparum remained unknown. Nowadays, in silico techniques are widely used to study the molecular interactions between compounds and proteins as they provide results quickly with high precision and accuracy. In this study, we aim to identify the potential molecular drug targets of knipholone in P. falciparum. We selected 10 proteins of P. falciparum with unique metabolic functions and we found that knipholone showed better binding affinity than the native ligands of 6 proteins. Out of the 6 proteins, knipholone showed better enzyme inhibitory potential than the native ligands of 4 proteins. We carried out a 100 ns MD simulations for knipholone and the native ligands of four proteins and this was followed by binding free energy calculations. In each step, the performance of knipholone was compared to the native ligands of the proteins. Knipholone outperformed the native ligand of Glutathione-S-Transferase (1OKT) at crucial computational studies as evidence from the lower protein–ligand root mean square deviation value, protein root mean square fluctuation value, and protein–ligand binding free energies. The ligand properties of knipholone provide additional evidence for its stability and it maintains adequate protein–ligand contacts during the entire simulation. The density functional theory study also supported the stability of knipholone at the active binding site of 1OKT. From the studied proteins, we conclude that Glutathione-S-Transferase is the most favorable drug target for knipholone in P. falciparum. Communicated by Ramaswamy H. Sarma

Structural and Molecular Determinants for Isoform Bias at Human Histamine H3 Receptor Isoforms

The human histamine H3 receptor (hH3R) is predominantly expressed in the CNS, where it regulates the synthesis and release of histamine and other neurotransmitters. Due to its neuromodulatory role, the hH3R has been associated with various CNS disorders, including Alzheimer's and Parkinson's disease. Markedly, the hH3R gene undergoes extensive splicing, resulting in 20 isoforms, of which 7TM isoforms exhibit variations in the intracellular loop 3 (IL3) and/or C-terminal tail. Particularly, hH3R isoforms that display variations in IL3 (e.g., hH3R-365) are shown to differentially signal via Gαi-dependent pathways upon binding of biased agonists (e.g., immepip, proxifan, imetit). Nevertheless, the mechanisms underlying biased agonism at hH3R isoforms remain unknown. Using a structure-function relationship study with a broad range of H3R agonists, we thereby explored determinants underlying isoform bias at hH3R isoforms that exhibit variations in IL3 (i.e., hH3R-445, -415, -365, and -329) in a Gαi-dependent pathway (cAMP inhibition). Hence, we systematically characterized hH3R isoforms on isoform bias by comparing various ligand properties (i.e., structural and molecular) to the degree of isoform bias. Importantly, our study provides novel insights into the structural and molecular basis of receptor isoform bias, highlighting the importance to study GPCRs with multiple isoforms to better tailor drugs.

Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications.

Insulin is a peptide responsible for regulating the metabolic homeostasis of the organism; it elicits its effects through binding to the transmembrane insulin receptor (IR). Insulin mimetics with agonistic or antagonistic effects toward the receptor are an exciting field of research and could find applications in treating diabetes or malignant diseases. We prepared five variants of a previously reported 20-amino acid insulin-mimicking peptide. These peptides differ from each other by the structure of the covalent bridge connecting positions 11 and 18. In addition to the peptide with a disulfide bridge, a derivative with a dicarba bridge and three derivatives with a 1,2,3-triazole differing from each other by the presence of sulfur or oxygen in their staples were prepared. The strongest binding to IR was exhibited by the peptide with a disulfide bridge. All other derivatives only weakly bound to IR, and a relationship between increasing bridge length and lower binding affinity can be inferred. Despite their nanomolar affinities, none of the prepared peptide mimetics was able to activate the insulin receptor even at high concentrations, but all mimetics were able to inhibit insulin-induced receptor activation. However, the receptor remained approximately 30% active even at the highest concentration of the agents; thus, the agents behave as partial antagonists. An interesting observation is that these mimetic peptides do not antagonize insulin action in proportion to their binding affinities. The compounds characterized in this study show that it is possible to modulate the functional properties of insulin receptor peptide ligands using disulfide mimetics.

A Pyridyl-1,2-azaborine Ligand for Phosphorescent Neutral Iridium(III) Complexes

A novel 1,2-azaborine (i.e., 4-methyl-2-(pyridin-2-yl)-2,1-borazaronaphthalene, 1a) has been synthesized and used for the first time as a B-N alternative to common cyclometalating ligands to obtain neutral phosphorescent iridium(III) complexes (i.e., 2a, 3, and 4) of general formula [Ir(C∧N)2(N∧NB)], where C∧N indicates three different cyclometalating ligands (Hppy = 2-phenylpyridine; Hdfppy = 2-(2,4-difluoro-phenyl)pyridine; Hpqu = 2-methyl-3-phenylquinoxaline). Moreover, the azaborine-based complex 2a was compared to the isoelectronic C═C iridium(III) complex 2b, obtained using the corresponding 2-(naphthalen-2-yl)pyridine ligand 1b. Due to the dual cyclometalation mode of such C═C ligand, the isomeric complex 2c was also obtained. All new compounds have been fully characterized by NMR spectroscopy and high-resolution mass spectrometry (MS), and the X-ray structure of 2a was determined. The electronic properties of both ligands and complexes were investigated by electrochemical, density functional theory (DFT), and photophysical methods showing that, compared to the naphthalene analogues, the azaborine ligand induces a larger band gap in the corresponding complexes, resulting in increased redox gap (basically because of the highest occupied molecular orbital (HOMO) stabilization) and blue-shifted emission bands (e.g., λmax = 523 vs 577 nm for 2a vs 2b, in acetonitrile solution at 298 K). On the other hand, the 3LC nature of the emitting state is the same in all complexes and remains centered on the pyridyl-borazaronaphthalene or its C═C pyridyl-naphthalene analogue. As a consequence, the quantum yields of such azaborine-based complexes are comparable to those of the more classical C═C counterparts (e.g., photoluminescence quantum yield (PLQY) = 16 vs 22% for 2a vs 2b, in acetonitrile solution at 298 K) but with enhanced excited-state energy. This proves that such type of azaborine ligands can be effectively used for the development of novel classes of photoactive transition-metal complexes for light-emitting devices or photocatalytic applications.

On the Edge of the Known: Extremely Electron-Rich (Di)Carboranyl Phosphines.

The syntheses of the first B9-connected carboranylphosphines (B9-Phos) featuring two carboranyl moieties as well as access to B9-Phos ligands with bulky electron-donating substituents, previously deemed unattainable, is reported. The electrochemical properties of the B9-Phos ligands were investigated, revealing the ability of the mesityl derivatives to form stabilized phosphoniumyl radical cations. The B9-Phos ligands display an extremely electron-releasing character surpassing that of alkyl phosphines and commonly used N-heterocyclic carbenes. This is demonstrated by their very small Tolman electronic parameters (TEPs) as well as extremely low P-Se coupling constants. Cone angles and buried volumes attest to the high steric demand exerted by the (di)carboranyl phosphines. The dicarboranyl phosphine AuI complexes show superior catalytic performance in the hydroamination of alkynes compared to the monocarboranyl phosphine analogs.

Crystal structures, antioxidant, electrochemical and in-situ spectroelectrochemical properties of new bisthiocarbohydrazones and their Ni(II) complexes

Four new isatin bisthiocarbohydrazone ligands (H2L1, H2L2, H2L3, H2L4) were synthesized by the condensation of salicylaldehyde, 5-bromosalicylaldehyde, 5-chlorosalicylaldehyde and 5-nitrosalicylaldehyde with isatin monothiocarbohydrazone, respectively. The mixed ligand Ni(II) complexes {[NiL1(P)], [NiL2(P)], [NiL3(P)] and [NiL4(P)]} containing triphenylphosphine (P: triphenylphosphine, PPh3) of these bisthiocarbohydrazone ligands were synthesized. The synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR, UV–Vis spectroscopy techniques and conductivity measurements. In the complexes, the bisthiocarbohydrazone ligands coordinate to nickel through ONS mode. The complexes are diamagnetic and exhibit square planar geometry. The crystal structures of two ligands, H2L1 and H2L3, and two complexes, [NiL1(P)] and [Ni3(L3)2(P)2], whose single crystals were obtained, were determined by single crystal X-ray diffraction technique. The crystal structure of [NiL1(P)] complex is monomeric and compatible with the structure of the solid complex. A new trinuclear Ni(II) complex, [Ni3(L3)2(P)2], was obtained by the crystallization of monomeric solid [NiL3(P)] complex in a different solvent mixture. Redox properties of bisthiocarbohydrazone ligands (H2L1-H2L4) bearing S1 or S2 substituents and their nickel(II) complexes {[NiL1(P)]-[NiL4(P)]} were investigated with cyclic voltammetry and in situ spectroelectrochemistry. Voltammetric analyses indicated that all ligands exhibited four quasi-reversible reduction and one irreversible oxidation process. Complexation of the ligands with Ni(II) cation decreased the number of the reduction processes and caused these processes to have more negative potentials. Significant spectral changes were also observed in the in situ spectroelectrochemical analysis due to electron transfer reactions. In addition, electrochemical responses of monosubstituted salicylaldehyde derivative isatin bisthiocarbohydrazone ligands and their nickel(II) complexes were compared with their disubstituted derivatives.

Nickel-Catalyzed Ligand-Controlled Selective Reductive Cyclization/Cross-Couplings.

ConspectusThe use of quaternary stereocenters during lead candidate optimization continues to grow because of improved physiochemical and pharmacokinetic profiles of compounds with higher sp3 fraction. Pd-catalyzed redox-neutral alkene difunctionalization involving carbopalladation of alkenes followed by nucleophilic-trapping σ-alkyl-palladium intermediates has been developed as an efficient method to construct quaternary stereocenters. However, the low chemoselectivity and air sensitivity of organometallic nucleophiles, as well as their low availability and accessibility, limit the scope of application of this elegant strategy. Recently, Ni-catalyzed reductive cross-coupling has evolved into a privileged strategy to easily construct valuable C(sp3)-C bonds. Despite great progress, the enantioselective coupling of C(sp3) electrophiles still relies on activated or functionalized alkyl precursors, which are often unstable and require multiple steps to prepare. Therefore, Ni-catalyzed reductive difunctionalization of alkenes via selective cyclization/cross-coupling was developed. This strategy not only offers a robust and practical alternative for traditional redox-neutral alkene difunctionalization but also provides strategic complementarity for reductive cross-coupling of activated alkyl electrophiles. In this Account, we summarize the latest results from our laboratory on this topic. These findings mainly include our explorations in modulating the enantioselectivity and cyclization mode of reductive cyclization/cross-couplings.We will first discuss Ni-catalyzed enantioselective reductive cyclization/cross-coupling to construct valuable chiral heterocycles with quaternary stereocenters and focus on the effects of ligands, reductants, and additives and their roles in reductive cross-coupling. A wide range of electrophiles have been explored, including aryl halides, vinyl halides, alkynyl halides, gem-difluoroalkenes, CO2, trifluoromethyl alkenes, and cyano electrophiles. The synthetic potential of this approach has also been demonstrated in the synthesis of biologically active natural products and drug molecules. Second, we will detail how to tune the steric effects of nickel catalysts by modifying bipyridine ligands for regiodivergent cyclization/cross-couplings. Specifically, the use of bidentate ligands favors exo-selective cyclization/cross-coupling, while the use of a carboxylic acid-modified bipyridine ligand permits endo-selective cyclization/cross-coupling. We will also show how to activate the amide substrate by altering the electronic and steric properties of substituents on the nitrogen, thereby enabling the nucleophilic addition of aryl halides to amide carbonyls. Further investigation of ligand properties has led to tunable cyclization/cross-couplings (addition to the amide carbonyl vs 7-endo-cyclization) for the divergent synthesis of pharmacologically important 2-benzazepine frameworks. Finally, we serendipitously discover that modifying the ligands of nickel catalysts and changing the oxidation state of nickel can control the migratory aptitude of different groups, thus providing a switchable skeletal rearrangement strategy. This transformation is of high synthetic value because it represents a conceptually unprecedented new approach to C-C bond activation. Thus, this Account not only summarizes synthetic methods that allow the formation of valuable chiral heterocycles with quaternary stereocenters using a wide variety of electrophiles but also provides insight into the relationship between ligand structure, substrate, and cyclization selectivity.

Recent Overview of Potent Antioxidant Activity of Coordination Compounds

During recent decades, the complexation of organic ligands toward several metal ions of s-p and d-block has been applied as a plan to enhance its antioxidant performance. Due to their wide range of beneficial impacts, coordination compounds are widely used in industries, specifically in the medicinal and pharmaceutical fields. The activity is generally improved by chelation consequently knowing that the characteristics of both ligands and metals can lead to the development of greatly active compounds. Chelation compounds are a substitute for using the traditional synthetic antioxidants, because metal chelates present benefits, including a variety in geometry, oxidation states, and coordination number, that assist and favor the redox methods associated with antioxidant action. As well as understanding the best studied anti-oxidative assets of these compounds, coordination compounds are involved in the free radical scavenging process and protecting human organisms from the opposing effects of these radicals. The antioxidant ability can be assessed by various interrelated systems. The methodological modification offers the most knowledge on the antioxidant property of metal chelates. Colorimetric techniques are the most used, though electron paramagnetic resonance (EPR) is an alternative for metallic compounds, since color does not affect the results. Information about systems, with their benefits, and restrictions, permits a dependable valuation of the antioxidant performance of coordination compounds, as well as assisting application in various states wherever antioxidant drugs are required, such as in food protection, appropriate good-packaged foods, dietary supplements, and others. Because of the new exhaustive analysis of organic ligands, it has become a separate field of research in chemistry. The present investigation will be respected for providing a foundation for the antioxidant properties of organic ligands, future tests on organic ligands, and building high-quality antioxidative compounds.

Ligand Decomposition during Nanoparticle Synthesis: Influence of Ligand Structure and Precursor Selection.

Aliphatic amine and carboxylic acid ligands are widely used as organic solvents during the bottom-up synthesis of inorganic nanoparticles (NPs). Although the ligands' ability to alter final NP properties has been widely studied, side reactivity of these ligands is emerging as an important mechanism to consider. In this work, we study the thermal decomposition of common ligands with varying functional groups (amines and carboxylic acids) and bond saturations (from saturated to polyunsaturated). Here, we investigate how these ligand properties influence decomposition in the absence and presence of precursors used in NP synthesis. We show that during the synthesis of inorganic chalcogenide NPs (Cu2ZnSnS4, Cu x S, and SnS x ) with metal acetylacetonate precursors and elemental sulfur, the ligand pyrolyzes, producing alkylated graphitic species. Additionally, there was less to no ligand decomposition observed during the sulfur-free synthesis of ZnO and CuO with metal acetylacetonate precursors. These results will help guide ligand selection for NP syntheses and improve reaction purity, an important factor in many applications.

Deciphering the interaction mechanism of natural actives against larval proteins of Aedes aegypti to identify potential larvicides: a computational biology analysis

Aedes aegypti is the target for repellents to curb incidences of vector-borne diseases. Stopping breeding of this mosquito species at its larval stages helps in controlling spread of insect-borne diseases. Therefore, the present study focused on deciphering the mechanism of interaction of selected natural actives against larval proteins of A. aegypti to identify potential natural alternative larvicides. 65 larval proteins were identified from literature, whose structures were modelled and validated using RaptorX and ProCheck. 11 natural actives were selected for predicting their ligand properties and toxicities via Toxicity Estimation Software Tool and ProTox-II. Molecular docking studies were carried out using POAP followed by 100 ns molecular dynamic simulation studies for top three best docked complexes to better understand the robustness of docking, complex stabilities and molecular mechanisms of interactions. Toxicity predictions revealed that 6 molecules belonged to toxicity class 4, and five to toxicity class 5, implying that they were all safe to use. Complexes goniothalamin-translation elongation factor (−10 kcal/mol), andrographolide-acetyl-CoA C-myristoyltransferase (−9.2 kcal/mol) and capillin-translation elongation factor (−8.4 kcal/mol) showed best binding energies. When simulated, capillin-translation elongation factor showed most stability, while the remaining two also evidenced robust docking. Evolutionary studies for top two larval proteins disclosed 100 other insect species in which these proteins can be targeted using various larvicides. Protein-protein interaction network analysis revealed several protein pathways that might be affected due to aforesaid naturals. Therefore, this study provides computational insights into the molecular interaction of naturals against larval proteins, acting as potential natural larvicides. Communicated by Ramaswamy H. Sarma

Phenylimido complexes of rhenium: fluorine substituents provide protection, reactivity, and solubility.

Reactions of [Re(NPhF)Cl3(PPh3)2] ({NPhF}2- = p-fluorophenylimide) with a variety of alkyl and aryl isocyanides have been studied. Different reactivity patterns and products have been obtained depending on the steric and electronic properties of the individual ligands. This involves the formation of 1 : 1 and 1 : 2 exchange products of Re(V) with the general formulae mer-[Re(NPhF)Cl3(PPh3)(isocyanide)] and cis- or trans-[Re(NPhF)Cl3(isocyanide)2]. The stability of the obtained products is correlated with the substitution pattern of the isocyanide ligands. The products have been studied by single-crystal X-ray diffraction and spectroscopic methods, including IR and multinuclear NMR spectroscopy as well as mass spectrometry. The use of partially fluorinated starting materials and ligands allows the modulation of the solubilities of the starting materials and the products as well as the monitoring of the reactions by means of 19F NMR. The attachment of the CF3 or F substituent on the isocyanides gives control over the steric bulk and the electronic properties of the ligands and, thus, their reactivity.

The coordination chemistry of 2,4,6-oxy functionalised 1,3,5-triphosphinines.

A number of stable group 6 metal complexes bearing 2,4,6-oxy functionalised 1,3,5-triphosphinines, phosphorus containing heterocyclic ligands with a central C3P3 core, were synthesised such that a complete series of [M{P3C3(OX)3}(CO)3] compounds is obtained [M = Cr(0), Mo(0), W(0); X = H, SitBuPh2, B(ipc)2]. In all complexes, the triphosphinine coordinates in a η6-binding mode via the delocalized 6π-system of the ring. The ligand properties can be tuned by changing the substituent on the oxygen centre. The π-electron accepting properties of the ligand increases in the following order: P3C3(OH)3 < P3C3(OSitBuPh2)3 < P3C3(OB(ipc)2)3. This trend is reflected in the structures determined by X-ray crystallography, and the ν(CO) stretching frequencies determined by IR spectroscopy. The collected data raise questions with respect to the frequently made assumption that phosphinines act as stronger π-acceptors with respect to arenes and thereby deplete electron density at the metal centres. With P3C3(OH)3 as an η6-coordinated ligand further molecules can be coordinated in the second coordination sphere via hydrogen bonds, which may be of interest for the construction of coordination polymers.

Nitron-derivative-based palladium carbene complexes: structural characterization, theoretical calculations, and catalytic applications in the Mizoroki-Heck coupling reaction.

New palladium(0) and palladium(ii) complexes with N-heterocyclic carbene (NHC) ligands derived from nitron and its derivatives were synthesized. The structures of most of these complexes were established by single-crystal X-ray diffraction studies. Among the new complexes, the palladium complex with a monodentate NHC ligand derived from nitron demonstrated the highest efficacy as a catalyst precursor in the Mizoroki-Heck coupling reaction of aryl chlorides with alkenes. Theoretical calculations provide valuable insights into the electronic parameters of both the ligands and the palladium complexes, highlighting the significance of a robust Pd-C bond and the π-accepting property of the NHC ligand in achieving enhanced catalytic activity. Notably, catalyst activation occurred much more rapidly with the preformed palladium(0) complex compared to its palladium(ii) counterpart.

Influence of ligands on the optical properties of rod-shaped Au25 nanoclusters.

In this study, we successfully synthesized rod-shaped [Au25(PPh3)10(S-Adm)5Cl2]2+ nanoclusters using kinetic controls. The complete molecular structure was determined by single-crystal X-ray crystallography and electrospray ionization mass spectrometry. In comparison with the previously reported [Au25(PPh3)10(PET)5Cl2]2+ clusters, both nanoclusters have an icosahedral composition of Au13 linked by Au atoms that share a vertex, but [Au25(PPh3)10(S-Adm)5Cl2]2+ clusters appear elongated due to the rigidity of adamantane. We conducted ultraviolet-visible spectrophotometry (UV-vis) measurements of [Au25(PPh3)10(PET)5Cl2]2+ and [Au25(PPh3)10(S-Adm)5Cl2]2+ in dichloromethane solvent to elucidate the modulation of the cluster properties of different ligands. The lowest energy absorption peak of [Au25(PPh3)10(S-Adm)5Cl2]2+ shifted to lower energies compared to the [Au25(PPh3)10(PET)5Cl2]2+ clusters in UV-vis measurements. Temperature-dependent absorption measurements revealed that [Au25(PPh3)10(S-Adm)5Cl2]2+ clusters were less affected by temperature compared to [Au25(PPh3)10(PET)5Cl2]2+. This result is attributed to the exciton phonon coupling of [Au25(PPh3)10(S-Adm)5Cl2]2+ clusters being weaker than [Au25(PPh3)10(PET)5Cl2]2+ clusters. Furthermore, the absorption spectra of [Au25(PPh3)10(PET)5Cl2]2+ and [Au25(PPh3)10(S-Adm)5Cl2]2+ clusters were measured using different types of solutions, and it was found that the lowest energy absorption peaks of [Au25(PPh3)10(S-Adm)5Cl2]2+ were shifted and affected by the solution at room temperature, which suggested that the [Au25(PPh3)10(S-Adm)5Cl2]2+ clusters with solution hydrogen bonds also interacted strongly at room temperature. Theoretical calculations show that changes in ligands affect the differences in the molecular orbitals and structures of the clusters, which cause changes in the optical properties.

Polarized Au(I)/Rh(I) bimetallic pairs cooperatively trigger ligand non-innocence and bond activation.

The combination of molecular metallic fragments of contrasting Lewis character offers many possibilities for cooperative bond activation and for the disclosure of unusual reactivity. Here we provide a systematic investigation on the partnership of Lewis basic Rh(I) compounds of type [(η5-L)Rh(PR3)2] (η5-L = (C5Me5)- or (C9H7)-) with highly congested Lewis acidic Au(I) species. For the cyclopentadienyl Rh(I) compounds, we demonstrate the non-innocent role of the typically robust (C5Me5)- ligand through migration of a hydride to the Rh site and provide evidence for the direct implication of the gold fragment in this unusual bimetallic ligand activation event. This process competes with the formation of dinuclear Lewis adducts defined by a dative Rh → Au bond, with selectivity being under kinetic control and tunable by modifying the stereoelectronic and chelating properties of the phosphine ligands bound to the two metals. We provide a thorough computational study on the unusual Cp* non-innocent behavior and the divergent bimetallic pathways observed. The cooperative FLP-type reactivity of all bimetallic pairs has been investigated and computationally examined for the case of N-H bond activation in ammonia.

Efficient emission of Zn(II) and Cd(II) complexes with nopinane-annelated 4,5-diazafluorene and 4,5-diazafluoren-9-one ligands: how slight structural modification alters fluorescence mechanism.

Zinc(II) and cadmium(II) chlorido complexes with an N,N-chelating nopinane-annelated 4,5-diazafluoren-9-one ligand (LO) were synthesized. While the zinc(II) complex is mononuclear and adopts a tetrahedral ZnN2Cl2 coordination geometry, its cadmium(II) analogue features a 1D polymeric structure due to the bridging coordination of chlorido ligands with Cd2+ ions having an octahedral CdN2Cl4 coordination geometry. The photophysical properties of the oxygen-containing LO ligand and its zinc(II) and cadmium(II) complexes were studied in solution and in the solid state and matched against the properties of its oxygen-free 4,5-diazafluorene congener L and its complexes of the same metal ions. Comprehensive experimental and theoretical studies revealed the impact of the oxygen atom in the ligand core on the luminescence of the ligands and the complexes. For the oxygen-free L ligand and L-based complexes, the structural differences between the S0 and S1 geometries are small, which leads to fluorescence with extraordinarily small Stokes shifts. The emission of these compounds is of locally excited character for L and of mixed locally excited + ligand-to-halide charge transfer character for the L-based complexes. The introduction of the oxygen atom in the ligand core results in a drastic red-shift of the emission band due to short-range charge transfer. The differences between the S0 and S1 geometries are much more pronounced for LO and LO-based compounds than those of their oxygen-free analogues, leading to an order of magnitude larger Stokes shifts. On going from solution to the solid state, LO and its complexes exhibit aggregation-induced emission (AIE) behaviour with photoluminescence quantum yields (PLQYs) reaching tens of percent.

An investigation of steric influence on the reactivity of FeV(O)(OH) tautomers in stereospecific C-H hydroxylation.

Two new tetradentate N4 ligands (LN4), LN4 = Me2,Me2PyzTACN (1-(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-4,7-dimethyl-1,4,7-triazacyclononane) and Me2,MeImTACN (1-((1-methyl-1H-imidazol-1-yl)methyl)-4,7-dimethyl-1,4,7-triazacyclononane) have been synthesized and their corresponding Fe(II) complexes [FeII(Me2,Me2PyzTACN)(CF3SO3)2], 1Pz, and [FeII(Me2,MeImTACN)(CF3SO3)2], 1Im, have been prepared and characterized. Complexes 1Pz and 1Im catalyse the hydroxylation of C-H bonds of alkanes with excellent efficiencies, using hydrogen peroxide as oxidant. The high H/D kinetic isotope effect values for C-H hydroxylation, large normalized tertiary/secondary C-H (C3/C2) bond selectivities in adamantane oxidation, and high degrees of stereoretention in the oxidation of cis-1,2-dimethylcyclohexane are indicative of metal-based oxidation processes. The complexes also catalyse the oxidation of cyclooctene to form its corresponding epoxide and syn-diol. For 1Pz the epoxide is the main product, while for the analogous complex 1Im the syn-diol predominates. The active oxidant is proposed to be an [(LN4)FeV(O)(OH)]2+ species (2Pz, LN4 = Me2,Me2PyzTACN and 2Im, LN4 = Me2,MeImTACN) which may exist in two tautomeric forms related by a proton shift between the oxo and hydroxo ligands. Isotope labelling experiments show that the oxygen atom in the hydroxylated products originates from both water and hydrogen peroxide, and labelling experiments involving oxygen atom transfer to sterically bulky substrates provide indirect information on the steric influence exerted by the two ligands in the relative reactivities of the two hypervalent iron tautomers. Based on these labelling studies, the steric influence exerted by each of the ligands towards the relative reactivity of the oxo ligands of the corresponding pair of Fe(V)(O)(OH) tautomers can be derived. Furthermore, this steric influence can be gauged relative to related complexes/ligands.

In-silico study for the identification of potential destabilizers between the spike protein of SARS-CoV-2 and human ACE-2

The emergence of the new SARS-CoV-2 virus, which causes the disease known as COVID-19, has generated a pandemic that has plunged the world into a health crisis. The infection process is triggered by the direct binding of the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) of the host cell. In the present study, virtual screening techniques such as molecular docking, molecular dynamics, calculation of free energy using the GBSA method, prediction of drug similarity, pharmacokinetic, and toxicological properties of various ligands interacting with the RBD-ACE2 complex were applied. The ligands radotinib, hinokiflavone, and ginkgetin were identified as potential destabilizers of the RBD-ACE2 interaction, which could produce their pharmacological effect by interacting at an allosteric site of ACE2, with affinity energy values of −10.2 ± 0.1, −9.8 ± 0.0, and −9.4 ± 0.0 kcal/mol, indicating strong receptor affinity. The complex with hinokiflavone showed the highest conformational stability and rigidity of the dynamic simulation and also obtained the best binding free energy of the three molecules, with an energy of −215.86 kcal/mol.