Abstract Sulfur-bridged multimetallic complexes provide a platform for probing long-range electronic communication relevant to metalloproteins and molecular electronic materials. Trimetallic complexes of the type (MN2S2)2Cu (M = [FeNO]2+ or [VO]2+), in which these two redox-active S = 1/2 spin probes are linked by a diamagnetic Cu(I) center in a tetrahedral S4 coordination environment, are developed. Structural analysis shows that the Cu(I) bridge enforces a twisted arrangement of the two MN2S2 units, in contrast to square-planar NiS4-bridged analogues, [ Quiroz, M.; et al., Chem. Sci.2023, 14, 9167–9174]. leading to distinct metal–ligand orbital alignment and sulfur-mediated bonding pathways. Despite a large interspin separation of approximately 6 Å between the spin probes, magnetic susceptibility measurements reveal appreciable ferromagnetic exchange coupling between these paramagnetic centers, although weaker than the coupling observed for the d8 (M′ = Ni(II), Pd(II), and Pt(II))-bridged stair-step complexes. These differences are attributed to the contrasting geometries of the CuS4 and M′S4 cores and their impact on superexchange through the bridging sulfurs. In addition to the solid-state X-ray crystallography, this new class of trimetallics was characterized by multiple methods including electrochemistry, vibrational spectroscopy, magnetic susceptibility, EPR, Mössbauer, and DFT computations. Redox and vibrational studies further probe electronic communication between the FeNO units: ν(NO) stretching frequency indicates that one-electron reduction is largely localized on a single FeNO center, whereas two-electron reduction leads to electron delocalization across both units. Together, these results demonstrate that copper-imposed geometric distortion modulates sulfur-mediated spin coupling and electron delocalization, providing design principles for multimetallic, spin-active architectures.

Boron-centered dinitrogen reduction is an emerging field that complements the corresponding transition-metal chemistry. Comprehensive thermodynamic and kinetic analysis by density functional theory (DFT) of the full N2 reduction process in a cyclic(alkyl)(amino)carbene (CAAC)-stabilized diborylene N2 complex, ((CAAC)(Dur)B)2(μ2-N2), reveals a spontaneous process under the mild conditions employed experimentally. Geometric and natural bond orbital analyses show N-N bond weakening in the early stages of N2 fixation. Frontier orbital analysis rationalizes the distinct geometries of the two key intermediates. The N2 adduct, ((CAAC)(Dur)B)2(μ2-N2), adopts an orthogonal arrangement of the two borylene fragments, whereas the diazene species, ((CAAC)(Dur)B)2(μ2-N2H2), has nearly coplanar fragments and a triplet ground state. In both, strong donation from the borylenes' highest occupied molecular orbitals (HOMOs) into the N2 or N2H2 π* orbitals weakens the N-N bond, while orbital-symmetry considerations dictate the observed skeletal orientations. Although experiments detect protonation exclusively at nitrogen, our calculations predict that protonation at boron is thermodynamically accessible for tri- and tetraprotonated intermediates by using stronger acids and weaker reductants. However, large kinetic barriers for B-to-N proton migration would prevent these boron-protonated isomers from contributing to productive N2 reduction. These insights provide clues for design principles for steering future main-group catalysts for ammonia synthesis.

Density functional theory (DFT) analyses of possible isomeric intermediates in the catalytic reduction of dinitrogen (N-2) to ammonia (NH3) by tris(phosphine)-anchored iron complexes (Anderson et al., 2013) [EP3Fe(N-2)](-) (E = B, C, Si, P = P(iPr)(2)) reveal distinct protonation preferences along alternative distal and proximal reduction pathways. Initial protonation strongly favors the distal nitrogen site for all three catalysts, whereas subsequent protonation shows more nuanced energetic biases, indicating potential mixed pathways. Particularly notable is the pronounced flexibility of the Fe-B bond, which facilitates electron storage and stabilizes highly reduced Fe centers, crucial for efficient N-2 activation. Transition state calculations identify prohibitively high activation barriers (> 40 kcal/mol) for intramolecular hydrogen migration between nitrogen atoms, effectively precluding interconversion between distal and proximal pathways during catalysis. Assessment of competitive hydrogen evolution reaction (HER) pathways reveals significant stabilization of Fe-H intermediates, which pose substantial thermodynamic barriers to catalyst regeneration. Our findings highlight the critical influence of the anchor atom on catalytic efficiency and selectivity, with boron's unique structural and electronic flexibility emerging as pivotal in optimizing biomimetic nitrogen fixation in these systems.

Fe(0) dinitrogen complexes [SiP3 R]Fe-N[triple bond, length as m-dash]N-Fe[SiP3 R] (1-R; [SiP3 R] = PhSi(CH2PR2)3; R = i Pr, Ph) are accessed by one- or two-electron reduction of Fe(i) and Fe(ii) chloride complexes [SiP3 i Pr]FeCl or κ2-[SiP3 R]FeCl2 (R = i Pr, Ph), respectively, and fully characterized by means of multinuclear NMR spectroscopy, single-crystal X-ray diffraction (SC-XRD), and Mössbauer spectroscopy. Complexes 1-R represent rare examples of bimetallic Fe(0) compounds with dinitrogen as a bridging ligand and have an overall spin of S = 0. Heating 1-R in the presence of SiH4 gas resulted in four-fold Si-H activation to furnish diiron complexes [SiP3 R](H)2Fe[double bond, length as m-dash]Si[double bond, length as m-dash]Fe(H)2[SiP3 R] (2-R; R = i Pr, Ph), which were characterized by multinuclear NMR spectroscopy, SC-XRD, Mössbauer spectroscopy, and density functional theory calculations. Complexes 2-R exhibit the shortest iron-silicon bonds to date and nearly linear Fe[double bond, length as m-dash]Si[double bond, length as m-dash]Fe cores. This work extends a previously developed strategy for SiH4 activation from cobalt to iron, while offering insight into the silicon-atom extrusion from SiH4 in molecular systems.

Bimetallic iron–dinitrogen complexes are developed which mediate the four-fold Si–H activation of SiH 4 to yield molecular diiron silicides. Experimental and computational results offer insight into bonding within the FeSiFe cores.

Extended fused 1,10-phenanthroline derivatives bearing heteroatoms at the inner rim, especially those extended into helical structures, are highly intriguing molecules for metal-ligand coordination and host-guest chemistry. However, such fully aromatic ligands have rarely been reported, possibly due to the combined synthetic challenges arising from ring strain, steric hindrance, and the coordination ability of nitrogen atoms on aromatic rings. Herein, we report two such derivatives: a coplanar ligand (4N7) and an expanded azahelicene (5N9) synthesized via thermodynamically driven multifold ring-closing olefin metathesis. Their structures were unambiguously confirmed by NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Both compounds exhibited strong binding affinities toward transition metals, with the Ag(I) complexes (Ag@4N7, Ag@5N9) showing the highest stability─substantially exceeding that of a nonfused, flexible analog (5N-OP). Thermodynamic analysis revealed that structural preorganization in the fused ligands imparts a significant entropic contribution to metal complexation. This work establishes thermodynamically driven ring-closing metathesis as a powerful approach for accessing synthetically challenging azahelicene ligands and highlights an entropy-based design principle for achieving highly efficient metal binding.

A diruthenium complex with a mu-CH3 ligand, [cis-{(eta 5-C5H2(t-Bu))2(CMe2)2}Ru2(dppm)2(mu-CH3)][B(ArF)4] (dppm = 1,1-bis(diphenylphosphino)methane) has been synthesized, structured, and its reactivity explored. Reaction of the mu-CH3 complex with H2 led to a fluxional dihydrogen/hydrido complex with the hydrogens exchanging between the two ruthenium centers, results consistent with the NMR spectroscopy, the crystal structure, and density functional theory. The activation barrier for this exchange was calculated to be similar to 12 kcal/mol. The mu-1,2-N2 complex formed when the mu-CH3 diruthenium or dimethyl diruthenium complexes were treated with acid, and the crystal structure showed a Ru-N-N-Ru geometry with a smaller Ru-N-N angle than other related complexes. The stability of a methane diruthenium complex with either a dppm or dmpm (1,1-bis(dimethylphosphino)methane) ligand has also been computationally investigated, with the less sterically demanding dmpm forming a more stable methane complex than that with the dppm ligand.

Photolysis of (η5-C5Me5)Ir(PPh3)(H)2 in benzene generates the 16-electron (16e-) complex (η5-C5Me5)Ir(PPh3) that undergoes competitive intramolecular ortho-metalation with a phenyl group from -PPh3 and intermolecular C-H activation with benzene. Previous density functional theory (DFT) studies identified the intramolecular π-complex and the intermolecular benzene π-complex intermediates and their corresponding C-H activation transition states. However, neither the mechanism of interconversion between these intermediates nor the origin of intramolecular versus intermolecular pathway selectivity has been established. Here, we characterized the open-shell 16e- iridium species and extensively mapped out the energy landscape for intramolecular ortho-metalation of -PPh3 versus intermolecular benzene C-H activation. Also, we performed DFT-based direct dynamics simulations, and the results suggest that the intramolecular versus intermolecular pathway selectivity is determined dynamically within picoseconds as the 16e- iridium species evolves into a coordinatively saturated structure. During this process, the π-complexes are formed concurrently with, instead of prior to, the iridium hydrides, which could not be explained by kinetic models that assume C-H cleavage as the rate-limiting step. These findings demonstrate that dynamics simulations in addition to DFT calculations are needed for a more complete mechanistic understanding of photoinduced C-H activation reactions, of which the product selectivity can be influenced by atomic motion.

The Ni-R active site in [NiFe]-hydrogenase features a bridging hydride between the Ni and Fe, displaced toward the Ni. However, all synthetic Ni-R models reported to date exhibit a hydride displaced toward Fe and display low turnover frequencies for H2 evolution. Understanding the factors governing the hydride position and activity of Ni-R and biomimetic complexes is crucial for developing efficient hydrogen-evolving catalysts. By utilizing the CCSD theory, DFT, NBO, and QTAIM analysis, we investigated these factors in a Ni-R active-site model (1), and two representative biomimetic complexes, 2* and 3. Our results reveal that the Ni site of 1 inherently prefers a square-planar [S2NiSH] configuration with an apically positioned thiolate and that hydride positioning is governed by the strength of [Ni-H-Fe] three-center two-electron bonding, which is modulated by the geometric torsion between the Ni terminal ligands and the bridging thiolates. By modifying the linkers between the Ni terminal ligands and bridging thiolate ligands of 2* and 3, we designed virtual biomimetic complexes (4-10). These complexes exhibit improved hydride nucleophilicity and increased potential for H2 formation, providing valuable insights into how geometric and electronic factors influence hydride activity and informing the design of more effective biomimetic hydrogenase models.

The delocalized, thermodynamically stable cation, [(N2S2)Fe(NO)•Fe(NO)2]+, an adduct of mono-nitrosyl and dinitrosyl iron units, is analyzed to address the unusual stability of the sulfur-bridged diiron complex in its three overall redox levels, +, 0, and -. X-ray diffraction and myriad spectroscopic techniques probe products of sequential electron uptake in the corresponding neutral and anionic species. Conundrums include unified blueshifts of the overall 3-band, ν(NO), pattern with added electrons. One-electron reduction changes the anti-ferromagnetically coupled, S = 0, cationic diiron species to the neutral analog, S = ½, with unpaired spin mainly localized on the MNIU, which decreases its ∠Fe-N-O angle by 10 degrees in response to the extra electron density. Subsequent reduction to the anionic species, S = 1, involves a major geometric change at the MNIU, which moves the Fe in {Fe(NO)}8 out of the N2S2 plane. Site-specific 15N labeling of nitrosyl in the MNIU confirms the IR analysis and shows rapid NO exchange between the MNIU/DNIU (mono-nitrosyl iron unit/dinitrosyl iron unit) pairs during its synthesis at RT. Mössbauer spectroscopy, S K-edge XAS, and molecular orbital calculations confirm the ability of NO and the versatility of sulfur bridges to buffer and distribute electrons, a key to their major importance in metalloenzymes.

The rational and controlled synthesis of metallo-organic cages using polyaromatic ligands is well established in the literature. There is a strong interest to advance this field towards the use of chiral ligands capable of yielding cages in a stereoselective manner. Herein, we demonstrate that the classical approach for designing metallo-organic cages can be translated to polyproline peptides, a biocompatible class of chiral ligands. We have successfully designed a series of polyprolines, which mimic the topology of ditopic polyaromatic ligands, to yield the stereoselective synthesis of a novel Pd lantern cage. This work will pave the way towards the stereospecific synthesis of more complex, functionalized peptide cages.

The templating properties of a diaza-nickel-cis-dithiolate towards triphenylphosphine gold(i), yielding a transoid [Ni(N2S2)2Au(PPh3)] complex (T. A. Pinder, S. K. Montalvo, A. M. Lunsford, C.-H. Hsieh, J. H. Reibenspies and M. Y. Darensbourg, Dalton Trans., 2014, 43, 138-144) suggested that a suitable analogue of d10-Au(i), i.e., {Ni(NO)}10, could generate a tetrahedral nickel node for a [Ni(N2S2)2Ni(NO)(X)]n coordination polymer. Monomeric precursors, derived from Feltham's [(Ph3P)2Ni(NO)(Cl)] (R. D. Feltham, Inorg. Chem., 1964, 3, 116-119) produced the bidentate/sulfur-chelated [Ni(N2S2)Ni(NO)(X)] species with loss of PPh3. Exchange of Cl- by azide, N3-, in the {Ni(NO)}10 synthon led to the balance of electrophilicity at Ni(NO) and non-covalent (H-bonding and van der Waals) interactions that stabilized the extended chain of bridging sulfurs, in transoid connectivities, between a square planar NiII and a tetrahedral Ni, the latter within the electronic and spin-delocalized {Ni(NO)}10 system. This study defines a new path that creates coordination polymers using metallodithiolates, the success of which, in this case, depends on the highly polarizable {Ni(NO)}10 unit.

Polymorphism, when a substance can exist in more than one crystalline form yet return to the same liquid or solution phase, is characterized by differences in packing or molecular conformation. Polymorphs often exhibit differing physical properties, and are therefore particularly important in the development of materials and pharmaceuticals. However, gaining a thorough understanding of the solid-state landscape of a molecule requires exhaustive experimental screening of crystallization conditions, a particular challenge when using classical crystallization methods. We show that high-throughput Encapsulated Nanodroplet Crystallization (ENaCt) can enable the rapid and efficient exploration of the solid-state landscape of highly polymorphic molecules, through an in-depth study of 5-methyl-2-((2-nitrophenyl)amino)thiophene-3-carbonitrile (ROY), the most polymorphic small molecule known. An ENaCt screen encompassing 1536 individual crystallization experiments, spanning 320 unique conditions, resulted in direct access to single crystals, suitable for X-ray diffraction analysis, for all six of the known polymorphs accessible from solution (Y, R, YN, ON, ORP and R18). In addition, two polymorphs (Y04 and Y19) previously accessed only via melt and heteroseeded melt experiments, and a new polymorph of ROY (O22) were obtained. Furthermore, ENaCt screening resulted in the identification of the first ROY solvate (ROY· methyl anthranilate) and the first example of a ROY dimer, formed via in situ oxidation. ENaCt is thus shown to be an impactful tool for the experimental mapping of the solid-state landscape of highly polymorphic molecules and, through the discovery of a new polymorph O22, has ensured that tetradecamorphic ROY retains the record for the most polymorphic small molecule.

We showed previously that the d(10) nickel perfluorocarbene complex, P3Ni=CF(CF3) [P = P((OPr)-Pr-i)(3)], 1, reacts with fluoroalkenes to produce both 4-membered nickelacycles and metathesis products via separate reaction pathways. Herein, we compare the reactivity of 1 with a variety of alkenes. The reaction of 1 with hexafluoropropene [CF2=CF(CF3), HFP] affords a single metallacycle, taking advantage of the diradical mechanism in which the carbene carbon adds to the CF2 end of HFP. In contrast, 1 and perfluoro(methyl vinyl ether), CF2=CF(OCF3), yield both metallacycle and metathesis products, with preferential formation of the more stabilized difluorocarbene [P3Ni=CF2 vs P3Ni=CF(OCF3)] and a higher ratio of metathesis to metallacycle products than using tetrafluoroethylene or vinylidene difluoride. Attempts to form fluoropolymers via ring-opening metathesis polymerization of perfluorocyclobutene and hexafluorocyclopentene briefly gave new nickel carbenes but then yielded Ni fluoroalkene complexes with the loss of the CF(CF3) unit. Surprisingly, both ethylene and styrene derivatives gave only metallacycles, although evidence was obtained for alkene coordination to nickel; computational studies are presented to identify the origin of these observations. Finally, insertion of ethylene into the ethylene-derived nickelacyclobutane afforded a new fluorinated alkene, CH2=CHCH2CH2CHFCF3, formed presumably via nickelacyclohexane through selective beta-H and reductive eliminations.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Bimetallic transition metal complexes with site-specific redox properties offer a versatile platform for understanding electron polarization, intramolecular electron transfer processes, and customizing electronic and magnetic properties that might impact reactivity and catalyst design. Inspired by the dissymmetric nickel sites in the Acetyl CoA Synthase (ACS) Active Site, three new bimetallic Ni(N2S2)-Ni(S2C2R2) complexes based on Ni(N2S2) metalloligand donor synthons, Nid, in mimicry of the nickel site distal to the redox-active iron sulfur cluster of ACS, and nickel dithiolene receiver units, designated as Nip, the nickel proximal to the 4Fe4S cluster, were combined to explore the influence of ligand environment on electronic structure and redox properties of each unit. The combination of synthons gave a matrix of three S-bridged dinickel complexes, characterized by X-ray crystallography, and appropriate spectroscopies. Computational modeling is connected to the electronic characteristics of the nickel donor and receiver units. This study demonstrated the intricacies of identifying sites of electrochemical redox processes, within multi-metallic systems containing non-innocent ligands.

Wheldone is a fungal metabolite isolated from the coculture of Aspergillus fischeri and Xylaria flabelliformis, displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.0]undeca-3,5-diene scaffold with a 2-hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for the structure to be revisited. Thus, the structure of wheldone has been revised using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single-crystal X-ray diffraction (SCXRD) analysis of a semisynthetic p-bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data now permits the unequivocal assignment of both the structure and absolute configuration of the natural product.

UV irradiation of yellow CH2Cl2 solutions of trans-Fe(CO)3(P((CH2)10)3P) (2a) and PMe3 (10 equiv) gives, in addition to the previously reported dibridgehead diphosphine P((CH2)10)3P (46%), a green paramagnetic complex that crystallography shows to be the trigonal-bipyramidal iron(I) radical trans-[Fe(CO)2(Cl)(P((CH2)10)3P)]• (1a•; 31% after workup). This is a rare example of an isolable species of the formula [Fe(CO)4-n(L)n(X)]• (n = 0-3, L = two-electron-donor ligand; X = one-electron-donor ligand). Analogous precursors with longer P(CH2)nP segments (n = 12, 14, 16, 18) give only the demetalated diphosphines, and a rationale is proposed. The magnetic susceptibility of 1a•, assayed by Evans' method and SQUID measurements, indicates a spin (S) of 1/2. Cyclic voltammetry shows that 1a• undergoes a partially reversible one-electron oxidation, but no facile reduction. The UV-visible, EPR, and 57Fe Mössbauer spectra are analyzed in detail. Complex 2a is similarly studied, and, despite the extra valence electron, exhibits a comparable oxidation potential (ΔE1/2 ≤ 0.04 V). The crystal structure shows a cage conformation, solvation level, disorder motif, and unit cell parameters essentially identical to those of 1a•. DFT calculations provide much insight regarding the structural, redox, and spectroscopic properties.

INTRODUCTION:Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways. OBJECTIVES:To prioritize the discovery of bioactive natural products and their biosynthetic pathways from these hundreds of high-confidence linkages, we developed a bioactivity-driven metabologenomics workflow combining quantitative chemical information, antiproliferative bioactivity data, and genome sequences. METHODS:The 110 fungi from our metabologenomics study were tested against multiple cancer cell lines to identify which strains produced antiproliferative natural products. Three strains were selected for further study, fractionated using flash chromatography, and subjected to an additional round of bioactivity testing and mass spectral analysis. Data were overlaid using biochemometrics analysis to predict active constituents early in the fractionation process following which their biosynthetic pathways were identified using metabologenomics. RESULTS:We isolated three new-to-nature stemphone analogs, 19-acetylstemphones G (1), B (2) and E (3), that demonstrated antiproliferative activity ranging from 3 to 5 µM against human melanoma (MDA-MB-435) and ovarian cancer (OVACR3) cells. We proposed a rational biosynthetic pathway for these compounds, highlighting the potential of using bioactivity as a filter for the analysis of integrated-Omics datasets. CONCLUSIONS:This work demonstrates how the incorporation of biochemometrics as a third dimension into the metabologenomics workflow can identify bioactive metabolites and link them to their biosynthetic machinery.

One electron oxidation of the monometallic alkenylacetylide complexes [Ru{C≡CC(R)=CH2}(dppe)Cp*] (1) and [Ru{C≡CC(R)=CH2}Cl(dppe)2] (2) (R = Ph (a); R = 4-MeS-C6H4 (b)) generates in each case a dinuclear bis(allenylidene) complex [{Ru}2{μ-C=C=C(R)–CH2–H2C–(R)C=C=C}][PF6]2 ({Ru} = Ru(dppe)Cp* ([3a,b][PF6]2); {Ru} = RuCl(dppe)2 ([4a,b][PF6]2), containing an unsaturated ethane bridge between both allenylidene moieties. Deprotonation of this ethane bridge results in the formation of the previously reported octa-3,5-diene-1,7-diyndiyl-bridged bimetallic species [{Ru}2{μ-C≡CC(R)=CH–HC=(R)CC≡C}] ({Ru} = Ru(dppe)Cp* (5a,b); {Ru} = RuCl(dppe)2 (6a,b). The isolation of these complexes illustrates a general synthetic route to these conjugated bimetallic species from monomeric alkenylacetylide precursors. Electrochemical and spectroelectrochemical investigations evince the ready formation of the representative redox series [5a]n+, and TD-DFT calculations performed on optimised structures featuring the simplified {Ru(dmpe)Cp} coordination sphere [{Ru(dmpe)Cp}2{μ-C≡CC(Ph)=HC–CH(Ph)CC≡C}]n+ ([5a†]n+) (n = 0, 1, 2) reveal significant delocalisation of the unpaired charge in the formally mixed-valent species (n = 1), consistent with Class III assignment within the Robin–Day classification scheme.