Unraveling Multicopper [Cu3] and [Cu6] Clusters with Rare µ3-Sulfato and Linear µ2-Oxido-Bridges as Potent Antibiofilm Agents against Multidrug-Resistant Staphylococcus aureus.

In this research article, two multicopper [Cu3] and [Cu6] clusters, [Cu3(cpdp)(µ3-SO4)(Cl)(H2O)2]·3H2O (1) and [Cu6(cpdp)2(µ2-O)(Cl)2(H2O)4]·2Cl (2) (H3cpdp = N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol), have been explored as potent antibacterial and antibiofilm agents. Their molecular structures have been determined by a single-crystal X-ray diffraction study, and the compositions have been established by thermal and elemental analyses, including electrospray ionization mass spectrometry. Structural analysis shows that the metallic core of 1 is composed of a trinuclear [Cu3] assembly encapsulating a µ3-SO42- group, whereas the structure of 2 represents a hexanuclear [Cu6] assembly in which two trinuclear [Cu3] motifs are exclusively bridged by a linear µ2-O2- group. The most striking feature of the structure of 2 is the occurrence of an unusual linear oxido-bridge, with the Cu3-O6-Cu3' bridging angle being 180.00°. Whereas 1 can be viewed as an example of a copper(II)-based compound displaying a rare µ3:η1:η1:η1 bridging mode of the SO42- group, 2 is the first example of any copper(II)-based compound showing an unsupported linear Cu-O-Cu oxido-bridge. Employing variable-temperature SQUID magnetometry, the magnetic susceptibility data were measured and analyzed exemplarily for 1 in the temperature range of 2-300 K, revealing the occurrence of antiferromagnetic interactions among the paramagnetic copper centers. Both 1 and 2 exhibited potent antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA BAA1717) and the clinically isolated culture of methicillin-resistant S. aureus (MRSA CI1). The mechanism of antibacterial and antibiofilm activities of these multicopper clusters was investigated by analyzing and determining the intracellular reactive oxygen species (ROS) generation, lipid peroxidation, microscopic observation of cell membrane disruption, membrane potential, and leakage of cellular components. Additionally, 1 and 2 showed a synergistic effect with commercially available antibiotics such as vancomycin with enhanced antibacterial activity. However, 1 possesses higher antibacterial, antibiofilm, and antivirulence actions, making it a potent therapeutic agent against both MRSA BAA1717 and MRSA CI1 strains.

Ancillary-Ligand-Assisted Variation in Nuclearities Leading to the Formation of Di-, Tri-, and Tetranuclear Copper(II) Complexes with Multifaceted Carboxylate Coordination Chemistry.

The self-assembly of a carboxylate-based dinucleating ligand, N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp), and copper(II) ions in the presence of various exogenous ancillary ligands results in the formation of the new dinuclear complex [Cu2(cpdp)(µ-Hisophth)]4·2H2isophth·21H2O (1), trinuclear complex [Cu3(Hcpdp)(Cl)4] (2), and tetranuclear complex [Cu4(cpdp)(µ-Hphth)(µ4-phth)(piconol)(Cl)2]·3H2O (3) (H2phth = phthalic acid; H2isophth = isophthalic acid; piconol = 2-pyridinemethanol; Cl- = chloride). In methanol-water, the reaction of H3cpdp with CuCl2·2H2O at room temperature leads to the formation of 2. On the other hand, 1 and 3 have been obtained by carrying out the reaction of H3cpdp with CuCl2·2H2O/m-C6H4(CO2Na)2 and CuCl2·2H2O/o-C6H4(CO2Na)2/piconol, respectively, in methanol-water in the presence of NaOH at ambient temperature. All three complexes have been characterized by elemental analysis, molar electrical conductivity and magnetic moment measurements, FTIR, UV-vis spectroscopy, and PXRD, including single-crystal X-ray structural analyses. The molecular structure of 1 is based on a µ-alkoxide and µ-isophthalate-bridged dimeric [Cu2] core; the structure of 2 represents a trimeric [Cu3] core in which a µ-alcohol-bridged dinuclear [Cu2] unit is exclusively coupled with a [CuCl2] species by two µ:η1:η1-syn-anti carboxylate groups forming a triangular motif; the structure of 3 embodies a tetrameric [Cu4] core, with two copper(II) ions in a distorted-octahedral coordination environment, one copper(II) ion in a distorted-trigonal-bipyramidal coordination environment, and the other copper(II) ion in a square-planar coordination environment. In fact, 2 and 3 represent rare examples of copper(II)-based multinuclear complexes showing outstanding features of rich coordination chemistry: (i) using a symmetrical dinucleating ligand, trinuclear complex 2 is generated with four- and five-coordination environments around copper(II) ions; (ii) the unsymmetrical tetranuclear complex 3 is obtained by using the same ligand with four-, five- and six-coordination environments around copper(II) ions; (iii) tetracopper(II) complex 3 shows four different bridging modes of carboxylate groups simultaneously such as µ:η2, µ:η1:η1, µ3:η2:η1:η1, and µ4:η1:η1:η1:η1, the µ4:η1:η1:η1:η1 mode of phthalate being unprecedented. The formation of these [Cu2], [Cu3], and [Cu4] complexes can be controlled by changing the exogenous ancillary ligands and pH of the reaction solutions, thus allowing an effective tuning of the self-assembly. The magnetic susceptibility measurements suggest that the copper centers in all three complexes are antiferromagnetically coupled. The thermal properties of 1-3 have been investigated by thermogravimetric and differential thermal analytical (TGA and DTA) techniques, indicating that the decomposition of all three complexes proceeds via multistep processes.

A Family of [Zn6] Complexes from the Carboxylate-Bridge-Supported Assembly of [Zn2] Building Units: Synthetic, Structural, Spectroscopic, and Systematic Biological Studies.

The three discrete [Zn6] complexes [Na3Zn6(cpdp)3(µ-Bz)3(CH3OH)6][ZnCl4][ZnCl3(H2O)]·3CH3OH·1.5H2O (1), [Na3Zn6(cpdp)3(µ-p-OBz)3(CH3OH)6]·2H2O (2), and [Na3Zn6(cpdp)3(µ-p-NO2Bz)3(CH3OH)6]Cl3·2H2O (3), supported by the carboxylate-based multidentate ligand N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp), have been successfully synthesized and fully characterized (Bz = benzoate; p-OBz = dianion of p-hydroxybenzoic acid; p-NO2Bz = p-nitrobenzoate). The complexes have been characterized by elemental analysis, FTIR, UV-vis, NMR spectroscopy, PXRD, and thermal analysis, including single-crystal X-ray crystallography of 1 and 2. The molecular architectures of 1-3 are built from the self-assembly of their corresponding [Zn2] units, which are interconnected to the central [Na3(CH3OH)6]3+ core by six endogenous benzoate groups, with each linking one Zn(II) and one Na(I) ion in a µ2:η1:η1-syn-anti bidentate fashion. The composition of the (cpdp3-)3/(Zn2+)6 complexes in 1-3 has been observed to be 1:2, on the basis of the UV-vis titration and NMR spectroscopic results, which is further supported by X-ray crystallography. Systematic biological studies performed with a mice model suggested possible antidiabetic efficacy as well as anticancer activities of the complexes. When complexes 1-3 were administered intraperitoneally in mice, 1 showed a lowering in the blood glucose level, overall maintenance of the pancreatic tissue mass, restriction of DNA damage in pancreatic cells, and retention of lipid droplet (LD) frequency, whereas 2 and 3 showed hepatic tissue mass consistency by inhibiting the DNA damage in hepatic cells, prior to the exposure to a potent diabetic inducer, alloxan (ALX). Similar trends of results were observed in inhibiting the generation of reactive oxygen species (ROS) in the pancreatic and hepatic cells, as examined by spectrofluorometric methods. Thus, 1 seems to be a better compound for overall diabetic management and control, whereas 2 and 3 seem to be promising compounds for designing chemopreventive drugs against hepatic carcinoma.

5-(Diarylimino)- and 5-(sulfoximido)dibenzothiophenium triflates: syntheses and applications as electrophilic aminating reagents.

The one-pot synthesis of well-defined 5-(diarylimino) and 5-(sulfoximido)dibenzothiophenium triflates, respectively from diarylimines or sulfoximines, is reported and the structures of a series of these compounds are elucidated by X-ray crystallography. In analogy to their hypervalent I(iii) analogues, the iminoyl and sulfoximidoyl groups of these compounds can be selectively transferred to organic substrates. Specifically, the uncatalyzed imination of thiols or sulfinates proceeds with good yields, while under the mild reaction conditions offered by visible light photoredox catalysis, the radical amination of hydrazones or the sulfoximidation of benzylic, allylic and propargylic C-H bonds takes place satisfactorily.

Storing redox equivalent in the phenalenyl backbone towards catalytic multi-electron reduction.

Storing and transferring electrons for multi-electron reduction processes are considered to be the key steps in various important chemical and biological transformations. In this work, we accomplished multi-electron reduction of a carboxylic acid via a hydrosilylation pathway where a redox-active phenalenyl backbone in Co(PLY-O,O)2(THF)2, stores electrons and plays a preponderant role in the entire process. This reduction proceeds by single electron transfer (SET) from the mono-reduced ligand backbone leading to the cleavage of the Si-H bond. Several important intermediates along the catalytic reduction reaction have been isolated and well characterized to prove that the redox equivalent is stored in the form of a C-H bond in the PLY backbone via a ligand dearomatization process. The ligand's extensive participation in storing a hydride equivalent has been conclusively elucidated via a deuterium labelling experiment. This is a rare example where the ligand orchestrates the multielectron reduction process leaving only the metal to maintain the conformational requirements and fine tunes the electronics of the catalyst.

A phenalenyl-based nickel catalyst for the hydroboration of olefins under ambient conditions.

In this report, nickel-catalyzed hydroboration of vinylarenes and aliphatic alkenes is investigated. The non-innocent phenalenyl ligand moiety in the nickel complex Ni(PLY)2(THF)2 (1) was utilized as an electron reservoir for the selective hydroboration reaction in the presence of pinacolborane under ambient conditions. The mechanistic investigations revealed that the alkene hydroboration reaction takes place through a single electron transfer (SET) from the phenalenyl ligand backbone leading to the cleavage of the B-H bond.

Transforming atmospheric CO2 into alternative fuels: a metal-free approach under ambient conditions.

This work demonstrates the first-ever completely metal-free approach to the capture of CO2 from air followed by reduction to methoxyborane (which produces methanol on hydrolysis) or sodium formate (which produces formic acid on hydrolysis) under ambient conditions. This was accomplished using an abnormal N-heterocyclic carbene (aNHC)-borane adduct. The intermediate involved in CO2 capture (aNHC-H, HCOO, B(OH)3) was structurally characterized by single-crystal X-ray diffraction. Interestingly, the captured CO2 can be released by heating the intermediate, or by passing this compound through an ion-exchange resin. The capture of CO2 from air can even proceed in the solid state via the formation of a bicarbonate complex (aNHC-H, HCO3, B(OH)3), which was also structurally characterized. A detailed mechanism for this process is proposed based on tandem density functional theory calculations and experiments.

A safe and efficacious Pt(ii) anticancer prodrug: design, synthesis, in vitro efficacy, the role of carrier ligands and in vivo tumour growth inhibition.

Diaminocyclohexane-Pt(ii)-phenalenyl complexes (1 and 2) showed an appropriate balance between efficacy and toxicity. Compound 2 showed nearly two-fold higher tumour growth inhibition than oxaliplatin in a murine NSCLC tumour model, when a combined drug development approach was used. The fluorescent properties of phenalenone were utilized to understand the mechanistic details of the drug.

Phosphatase-like Activity of Tetranuclear Iron(III) and Zinc(II) Complexes.

Three new tetranuclear iron(III) and zinc(II) complexes, [Fe4(cpdp)2(phth)2(OH)2]·8H2O (1), [Fe4(cpdp)2(terephth)2(OH)2] (2), and [Zn4(Hcpdp)2(suc)]Br2·12H2O (3), have been synthesized as models for the active site of phosphoester hydrolases by utilizing a polydentate ligand, N, N'-bis[2-carboxybenzomethyl]- N, N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp) in combination with exogeneous phthalate (phth), terephthalate (terephth), and succinate (suc). Single crystal X-ray analyses reveal that the metallic core of complex 1 consists of four distorted octahedral iron(III) ions with average intraligand Fe---Fe separation of 3.656(2) Å, while the structure 3 represents a tetranuclear metallic core containing four distorted trigonal bipyramidal zinc(II) ions with average intraligand Zn---Zn separation of 3.472(2) Å. The molecular structure of complex 2 has been optimized by the DFT method which shows that its core arrangement is similar to that of 1. Complex 1 has a very interesting centrosymmetric structure that includes two crystallographically equivalent [Fe2(cpdp)]3+ dinuclear units, connected together by a pair of syn-syn bridging phthalates and a pair of bridging hydroxides to generate a "dimer of dimers" structural motif. In complex 3, a succinate group connects two crystallographically equivalent [Zn2(Hcpdp)]2+ dinuclear units in a syn-syn bidentate manner forming a "dimer of dimers" structural design. All three complexes show phosphatase-like activity that has been examined in methanol-water (1:1; v/v) using bis( p-nitrophenyl) phosphate (BNPP) as model substrate by applying the UV-vis spectrophotometric technique. In each case, the kinetic data have been analyzed by the Michaelis-Menten approach. The order of catalytic efficiency for the conversion of substrate to product follows the trend 1 > 2 > 3 with turnover rates ( kcat) of (2.73 ± 0.13) × 10-5 for 1, (1.06 ± 0.07) × 10-5 for 2, and (2.33 ± 0.18) × 10-6 s-1 for 3. These kcat values are comparable to, albeit slightly lower than, the values reported for similar iron(III)- and zinc(II)-based model complexes in the literature. DFT calculations have been carried out to support the proposed mechanism for phosphatase-like activity.

Tuning the redox non-innocence of a phenalenyl ligand toward efficient nickel-assisted catalytic hydrosilylation.

In this report, a ligand-redox assisted catalytic hydrosilylation has been investigated. A phenalenyl ligand coordinated nickel complex has been utilized as an electron reservoir to develop a base metal-assisted catalyst, which very efficiently hydrosilylates a wide variety of olefin substrates under ambient conditions. A mechanistic investigation revealed that a two-electron reduced phenalenyl based biradical nickel complex plays the key role in such catalysis. The electronic structure of the catalytically active biradical species has been interrogated using EPR spectroscopy, magnetic susceptibility measurements, and electronic structure calculations using a DFT method. Inhibition of the reaction by a radical quencher, as well as the mass spectrometric detection of two intermediates along the catalytic loop, suggest that a single electron transfer from the ligand backbone initiates the catalysis. The strategy of utilising the redox reservoir property of the ligand ensures that the nickel is not promoted to an unfavorable oxidation state, and the fine tuning between the ligand and metal redox orbitals elicits smooth catalysis.

Accessing Heterobiaryls through Transition-Metal-Free C-H Functionalization.

Herein we report a transition-metal-free synthetic protocol for heterobiaryls, one of the most important pharmacophores in the modern drug industry, employing a new multidonor phenalenyl (PLY)-based ligand. The current procedure offers a wide substrate scope (24 examples) with a low catalyst loading resulting in an excellent product yield (up to 95%). The reaction mechanism involves a single electron transfer (SET) from a phenalenyl-based radical to generate a reactive heteroaryl radical. To establish the mechanism, we have isolated the catalytically active SET initiator, characterizing by a magnetic study.

Highly Active Carbene Potassium Complexes for the Ring-Opening Polymerization of ε-Caprolactone.

Herein we report the synthesis of two complexes of potassium employing strongly nucleophilic carbenes, such as cyclic "(alkyl)(amino)carbene (cAAC) and abnormal N-heterocyclic carbene (aNHC). Both complexes are dimeric in the solid state and the two potassium centers are bridged by trimethylsilylamide. In these complexes, the carbene- - -K interaction is predominantly electrostatic in character, which has been probed thoroughly by NBO and AIM analyses. Indeed, the delocalization energy of the cAAC lone pair calculated from the second-order perturbation theory was only 5.21 kcal mol-1, supporting a very weak interaction. The solution-state behavior of these molecules, as inferred from NOESY spectra, hints that the weak carbene- - -K interaction is retained in nonpolar solvents, and the bond is not dissociated at least on the NMR time scale. We took advantage of such a weak interaction to develop highly effective ring-opening polymerization catalysts for ε-caprolactone and rac-lactide. The efficacy of these catalysts is prominent from a very high substrate/metal-initiator ratio as well as very low dispersity index of the obtained polymer chains, reflecting significant control over polymerization.

A new face of phenalenyl-based radicals in the transition metal-free C-H arylation of heteroarenes at room temperature: trapping the radical initiator via C-C σ-bond formation.

The radical-mediated transition metal-free approach for the direct C-H bond functionalization of arenes is considered as a cost effective alternative to transition metal-based catalysis. An organic ligand-based radical plays a key role by generating an aryl radical which undergoes a subsequent functionalization process. The design principle of the present study takes advantage of a relatively stable odd alternant hydrocarbon-based phenalenyl (PLY) radical. In this study, the first transition metal-free catalyzed direct C-H arylation of a variety of heteroarenes such as azoles, furan, thiophene and pyridine at room temperature has been reported using a phenalenyl-based radical without employing any photoactivation step. This protocol has been successfully applied to the gram scale synthesis of core moieties of bioactive molecules. The phenalenyl-based radical initiator has been characterized crystallographically by trapping it via the formation of a C-C σ-bond between the phenalenyl radical and solvent-based radical species.

ICT-Isomerization-Induced Turn-On Fluorescence Probe with a Large Emission Shift for Mercury Ion: Application in Combinational Molecular Logic.

A unique turn-on fluorescent device based on a ferrocene-aminonaphtholate derivative specific for Hg2+ cation was developed. Upon binding with Hg2+ ion, the probe shows a dramatic fluorescence enhancement (the fluorescence quantum yield increases 58-fold) along with a large red shift of 68 nm in the emission spectrum. The fluorescence enhancement with a red shift may be ascribed to the combinational effect of C═N isomerization and an extended intramolecular charge transfer (ICT) mechanism. The response was instantaneous with a detection limit of 2.7 × 10-9 M. Upon Hg2+ recognition, the ferrocene/ferrocenium redox peak was anodically shifted by ΔE1/2 = 72 mV along with a "naked eye" color change from faint yellow to pale orange for this metal cation. Further, upon protonation of the imine nitrogen, the present probe displays a high fluorescence output due to suppression of the C═N isomerization process. Upon deprotonation using strong base, the fluorescence steadily decreases, which indicates that H+ and OH- can be used to regulate the off-on-off fluorescence switching of the present probe. Density functional theory studies revealed that the addition of acid leads to protonation of the imine N (according to natural bond orbital analysis), and the resulting iminium proton forms a strong H-bond (2.307 Å) with one of the triazole N atoms to form a five-membered ring, which makes the molecule rigid; hence, enhancement of the ICT process takes place, thereby leading to a fluorescence enhancement with a red shift. The unprecedented combination of H+, OH-, and Hg2+ ions has been used to generate a molecular system exhibiting the INHIBIT-OR combinational logic operation.

Inorganic Phosphate and Arsenate within New Tetranuclear Copper and Zinc Complexes: Syntheses, Crystal Structures, Magnetic, Electrochemical, and Thermal Studies.

Three, PO4 3-/HPO4 2- and AsO4 3--incorporated, new tetranuclear complexes of copper(II) and zinc(II) ions have been synthesized and fully characterized. In methanol-water, reactions of H3cpdp (H3cpdp = N,N'-Bis[2-carboxybenzomethyl]-N,N'-Bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol) with copper(II) chloride in the presence of either NaOH/Na2HPO4·2H2O or KOH/Na2HAsO4·7H2O lead to the isolation of the tetranuclear complexes Na3[Cu4(cpdp)2(µ4-PO4)](OH)2·14H2O (1) and K2[Cu4(cpdp)2(µ4-AsO4)](OH)·162/3H2O (2), respectively. Similarly, the reaction of H3cpdp with zinc(II) chloride in the presence of NaOH/Na2HPO4·2H2O yields a tetranuclear complex, Na(H3O)2[Zn4(cpdp)2(µ4-HPO4)]Cl3·121/2H2O (3). All complexes are characterized by single-crystal X-ray diffraction and other analytical techniques, such as Fourier transform infrared and UV-vis spectroscopy, thermogravimetric and electrochemical studies. The solid-state molecular framework of each complex contains two monocationic [M2(cpdp)]+ (M = Cu, Zn) units, which are exclusively coordinated to either phosphate/hydrogen phosphate or arsenate groups in a unique mode. All three complexes exhibit a µ4:η1:η1:η1:η1 bridging mode of the PO4 3-/HPO4 2-/AsO4 3- groups, with each bridging among four metal ions. The thermal properties of all three complexes have been investigated by thermogravimetric analysis. Low-temperature magnetic studies of complexes 1 and 2 disclose moderate antiferromagnetic interactions mediated among the copper centers through alkoxide and phosphate/arsenate bridges. Electrochemical studies of complexes 1 and 2 in dimethylformamide using cyclic voltammetry reveal the presence of a fairly assessable one-electron metal-based irreversible reduction and one quasireversible oxidation couple.

Metal-Free Reduction of CO2 to Methoxyborane under Ambient Conditions through Borondiformate Formation.

An abnormal N-heterocyclic carbene (aNHC) based homogeneous catalyst has been used for the reduction of carbon dioxide to methoxyborane in the presence of a range of hydroboranes under ambient conditions and resulted in the highest turnover number of 6000. A catalytically active reaction intermediate, [aNHC-H⋅9BBN(OCOH)2 ] was structurally characterized and authenticated by NMR spectroscopy. A detailed mechanistic cycle of this catalytic process via borondiformate formation has been proposed from tandem experimental and computational experiments.

An abnormal N-heterocyclic carbene based nickel complex for catalytic reduction of nitroarenes.

Herein we report the synthesis of a nickel(ii) dichloro complex bearing an abnormal N-heterocyclic carbene (aNHC). The NiCl2(aNHC)2 complex has been used as an efficient catalyst for the reduction of nitroarenes with hydrosilanes to give aromatic amines in good to excellent yields. This catalytic protocol can tolerate functional groups such as halides, alkenes or nitriles. Furthermore, the longevity of the catalyst was tested in successive catalytic cycles, which indicates a sustained catalytic activity over multiple catalytic cycles.

Switching closed-shell to open-shell phenalenyl: toward designing electroactive materials.

Open-shell phenalenyl chemistry started more than half a century back, and the first solid-state phenalenyl radical was realized only 15 years ago highlighting the synthetic challenges associated in stabilizing carbon-based radical chemistry, though it has great promise as building blocks for molecular electronics and multifunctional materials. Alternatively, stable closed-shell phenalenyl has tremendous potential as it can be utilized to create an in situ open-shell state by external spin injection. In the present study, we have designed a closed-shell phenalenyl-based iron(III) complex, Fe(III)(PLY)3 (PLY-H = 9-hydroxyphenalenone) displaying an excellent electrocatalytic property as cathode material for one compartment membraneless H2O2 fuel cell. The power density output of Fe(III)(PLY)3 is nearly 15-fold higher than the structurally related model compound Fe(III)(acac)3 (acac = acetylacetonate) and nearly 140-fold higher than an earlier reported mononuclear Fe(III) complex, Fe(III)(Pc)Cl (Pc = pthalocyaninate), highlighting the role of switchable closed-shell phenalenyl moiety for electron-transfer process in designing electroactive materials.