Ligand Substitution Reactions Research Articles

Differential impact on oral cancer cell viability for three carboxylate-stabilized rhenium(I) tricarbonyl centers supported by 2,2′-bipyridine: One-pot synthesis, a structure, and proton-catalyzed carboxylate ligand substitution

A set of six carboxylate-stabilized rhenium(I) tricarbonyl complexes supported by a 2,2′-bipyridine (bpy) ligand, Re(O2CR)(CO)3(bpy) (R = H, CH3, CHF2, R- or S-CHBrCH(CH3)2, and C5H11), were prepared by acidolysis of the complex Re(OCO2C5H11)(CO)3(bpy) with the appropriate carboxylic acid and characterized by 1H and 13C-{1H} NMR and IR spectroscopy. The crystal structure of the complex, Re[R-O2CCHBrCH(CH3)2](CO)3(bpy), was determined by X-ray crystallography. An alternate one-pot route to the carboxylate-stabilized rhenium(I) complexes Re(O2CR’)(CO)3(bpy) (R’ = CH3 or C6H5) and Re(O2CCH3)(CO)3(1,10-pheanthroline), which starts with Re2(CO)10 and in which an ester solvent serves as the source of the carboxylate ligand, was also developed. Cell viability tests on three carboxylate-stabilized rhenium(I) complexes (R = H, CH3, or CHF2), using the HSC-2 oral cancer cell line, found different levels of cytotoxicity for each complex. NMR studies of the carboxylate ligand substitution reaction found that the reaction is catalyzed by protons. In a chloride-rich NMR solution, substitution of the carboxylate ligand leads to either a chloride-stabilized neutral complex (major product) or to a water-stabilized cation (minor product). Cytotoxicity results correlate positively with the Kb value of the carboxylate ligand. Apparently, the more substitutionally inert the carboxylate-stabilized complex is in a chloride-rich environment (similar to extracellular fluid) the greater the amount of cytotoxic [Re(CO)3(bpy)(H2O)]+ that forms in the cytosol.

Regulating Access to Active Sites via Hydrogen Bonding and Cation-Dipole Interactions: A Dual Cofactor Approach to Switchable Catalysis.

Hydrogen bonding networks are ubiquitous in biological systems and play a key role in controlling the conformational dynamics and allosteric interactions of enzymes. Yet in small organometallic catalysts, hydrogen bonding rarely controls ligand binding to the metal center. In this work, a hydrogen bonding network within a well-defined organometallic catalyst works in concert with cation-dipole interactions to gate substrate access to the active site. An ammine ligand acts as one cofactor, templating a hydrogen bonding network within a pendent crown ether and preventing the binding of strong donor ligands, such as nitriles, to the nickel center. Sodium ions are the second cofactor, disrupting hydrogen bonding to enable switchable ligand substitution reactions. Thermodynamic analyses provide insight into the energetic requirements of the different supramolecular interactions that enable substrate gating. The dual cofactor approach enables switchable catalytic hydroamination of crotononitrile. Systematic comparisons of catalysts with varying structural features provide support for the critical role of the dual cofactors in achieving on/off catalysis with substrates containing strongly donating functional groups that might otherwise interfere with switchable catalysts.

The Role of the Lowest Excited Triplet State in Defining the Rate of Photoaquation of Hexacyanometalates.

Photosolvation is a type of ligand substitution reaction started by irradiation of a solution with light, triggering the replacement of a ligand with a molecule from the solvent. The excited state is created through many possible pathways. For the class of hexacyanides of groups 8 and 9 of the periodic table, irradiation in the ligand field band is followed by intersystem crossing to the lowest excited triplet state, which we propose to mediate the photoaquation reaction in this class of complexes. In this study, we present time-resolved X-ray absorption data showing indications of the triplet intermediate state in the cobalt(III) hexacyanide complex and we discuss general aspects of the photoaquation reaction in comparison with reported data on the isoelectronic iron(II) hexacyanide. Quantum chemical calculations are analyzed and suggest that the nature of the lowest excited triplet state in each complex can explain the drastically different rate of reactions observed.

Computational study of core modified dipyriamethyrin for the competitive complexation of Am3+/Cm3+ from their trichlorides.

In the process of handling and storage of radioactive actinides it is essential to selectively sequester the minor actinides, such as Am and Cm, through a competitive complexation process. Herein we computationally designed two core modified ligands (L21- and L3) through systematic oxygen substitution at the NH sites of dipyriamethyrin (L1_2H), a hexadentate expanded porphyrin, and studied their competitive complexation towards trivalent actinides (An = Am/Cm) from their trichlorides using density functional theory (DFT). We observed shorter An-N bonds and longer An-O bonds in complexes based on core modified ligands (L21- and L3). The An-Cl bond length increases with increasing axial coordination number (i.e., from L12- to L3) to accommodate the ligands. All the bonds were identified to be electrostatic in nature. L12- exhibits shorter bonds and larger bond orders on complexing with Am than with Cm. On moving from complexes of L21- to L3, the An-N bond lengths are shortened, while An-O bond lengths become larger. Between the complexes of Am and Cm, there is marginal difference in their bond distances with L21- and L3. Charge analysis shows ligand to metal charge transfer during coordination, with back-donation from An to N/O and Cl. The calculated spin-density analysis indicates that An remains in its trivalent oxidation state on complexation, while orbital occupation analysis shows that the 5f and 6d orbitals are involved in bonding; this was confirmed by molecular orbital (MO) analysis that shows the complexes of L21- and L3 to exhibit higher degeneracy in their overlapping MOs. Further, the energy decomposition analysis (EDA) confirms that all ionic bonds are primarily due to electrostatic contributions, where the orbital contributions increase from L12- to L3 complexes and maximum covalency was observed in Cm complexes due to the energy matching between the 5f orbitals of Cm and the 2p orbitals of N and Cl, compared to Am. To confirm the competitiveness in the complexation of the ligand towards Am vs. Cm, the thermodynamic parameters were analysed for the ligand and metal substitution reactions. L12- shows more affinity towards Am than Cm, while L21- and L3 prefer Cm.

Quantification of alpha-lipoic acid in pharmaceutical samples using Pd(II) catalyzed ligand substitution reaction in SLS micellar medium

Quantification of alpha-lipoic acid in pharmaceutical samples using Pd(II) catalyzed ligand substitution reaction in SLS micellar medium

Steric effect on the photoreaction of chromium(III) porphyrin complexes with imidazole ligands

The steric effect in the photoreaction and ligand substitution reaction of axially coordinated imidazole ligands in chromium(III) porphyrin complexes was investigated in toluene. Imidazole ligands that have various alkyl substituents at the carbon atom [Formula: see text] to the coordinating nitrogen atom were used. The quantum yield of the photodissociation reaction of the axial imidazole ligand shows a remarkable steric effect. Reflecting the steric bulkiness, the magnitude of the quantum yield is isopropyl > ethyl > methyl > (H). The steric effect also appears in the thermal ligand substitution reactions. The mechanism of the steric effect on reactivity will be discussed in terms of the steric hindrance between the porphyrin ligand and the alkyl substituents of imidazole.

Synergistic Induction of Solvent and Ligand-Substitution in Single-Crystal to Single-Crystal Transformations toward a MOF with Photocatalytic Dye Degradation.

External-stimuli responsiveness as found in natural organisms and smart materials is attractive for functional materials scientists who attempt to design and imitate fascinating behavior into their materials. Herein, we report a couple of new solvent-responsive isostructural two-dimensional cationic metal-organic frameworks (MOFs) of Mn(II) (1a) and Zn(II) (2a) that undergo unprecedented single-crystal to single-crystal (SCSC) transformation toward the corresponding isostructural three-dimensional MOFs of Mn(II) (1b) and Zn(II) (2b). The 2D MOFs 1a and 2a have been effortlessly and rapidly synthesized via the microwave-heating technique. The SCSC transformations are synergistically induced by solvent and ligand-substitution reactions and able to be triggered by water, methanol, ethanol, and n-propanol. Time-dependent SCSC transformations were studied by in situ X-ray diffraction. Investigations on photodegradation of methyl orange showed that Zn-MOF 2b has higher efficiency than Mn-MOF 1b under UV-C irradiation at 300 min, 94.27%, and 21.91%, respectively. The influence of charge on the dye molecules, heterogeneity of the catalysis, and •OH radical-scavenging test was studied. First-principles computations suggest that the high photocatalytic activity of 2b may be attributed to its suitable band-edge position for redox reactions.

Three heteroleptic copper(I) complexes with [Cu(P˄P)N2]+ structure and their fluorescence sensing for VOCs

The design and research of luminescent and volatile organic compound (VOC) fluorescent sensing materials are of great significance and challenge. We report herein the ligand substitution reaction and VOC sensing of new heteroleptic [Cu(P˄P)N2]+ type copper(I) complexes. Firstly, three new complexes 1–3 were designed by utilizing a chelate diphosphine ligand 4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene (Xantphos) and synthesized by the substitution reaction of different N‐containing ligands of 4‐PBO (1), 3‐PBO (2), and 4,4′‐Bipy (3) (4‐PBO = 2‐(4′‐pyridyl)‐benzoxazole, 3‐PBO = 2‐(3′‐pyridyl)‐benzoxazole, 4,4′‐Bipy = 4,4′‐bipyridine), respectively. Three complexes were characterized by elemental analysis, spectroscopic analysis (IR, UV–Vis), single‐crystal X‐ray diffraction (SCXRD), and photoluminescence study. The SCXRD study revealed that complexes 1 and 2 both exhibit a molecular structure with tetrahedral copper(I) complex cation and hexafluorophosphate anion, while complex 3 differs in that its cation is a binuclear copper(I) structure bridged by 4,4′‐bipyridine. Three complexes 1–3 present supramolecular ribbon, supramolecular dimer, and supramolecular framework structure, respectively. Some differences of their UV–Vis absorption spectra were explained by TD‐DFT calculation and wavefunction analysis. It is found that 1 has an abnormal luminescence blue shift, and a luminescence mechanism through the high‐energy T2 excited state is proposed by TD‐DFT calculation. Based on 3, a fluorescent test strip was developed, and its fast and selective fluorescent sensing of pyridine vapor through quenching mechanism was successfully realized. The fluorescent quenching mechanism of the material was also studied, and it was proposed that the quenching should be attributed to the photoinduced electron transfer (PET) mechanism.

Electronic and ring size effects of N-heterocyclic carbenes on the kinetics of ligand substitution reactions and DNA/protein interactions of their palladium(II) complexes

The synthesis, substitution kinetics and DNA/BSA interactions of four cationic Pd(II) complexes [Pd(1)Cl]BF4 (Pd1), [Pd(2)Cl]BF4 (Pd2), [Pd(3)Cl]BF4 (Pd3) and [Pd(4)Cl]BF4 (Pd4), derived from the reaction of [PdCl2(NCCH3)2] with ligands 2,6-bis(3-methylimidazolium-1-yl)pyridine dibromide (1), 2,6-bis(3-ethylimidazolium-1-yl)pyridine dibromide (2), 2,6-bis(1-methylimidazole-2-thione)pyridine (3), and 2,6-bis(1-ethylimidazole-2-thione)pyridine (4), respectively are reported. The complexes were characterised by various spectroscopic techniques and single crystal X-ray diffraction for compound Pd2. Kinetic reactivity of the complexes with the biologically relevant nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5′-monophosphate sodium salt (5’-GMP) was in the order: Pd1 > Pd2 > Pd3 > Pd4, which was largely dependent on the electronic and ring size of the chelate ligands, consistent with Density functional theory (DFT) simulations. The interactions of the complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) binding titrations showed strong binding. Both the experimental and in silico data reveal CT-DNA intercalative binding mode.Graphical abstract

Reactivity of non-organometallic ruthenium(II) polypyridyl complexes and their application as catalysts for hydride transfer reactions.

Recently, we investigated the substitution behavior of a series of ruthenium(II) complexes of the general formula [RuII(terpy)(N∧N)Cl]Cl, where terpy = 2,2':6',2″-terpyridine, N∧N = bidentate ligand, in aqueous solutions. We have shown that the most and least reactive complexes of the series are [RuII(terpy)(en)Cl]Cl (en = ethylenediamine) and [RuII(terpy)(phen)Cl]Cl (phen = 1, 10-phenantroline), respectively, as a result of different electronic effects provided by the bidentate spectator chelates. Polypyridyl amine Ru(II) complex, viz. [Ru(terpy)(en)Cl]Cl and [Ru(terpy)(ampy)Cl]Cl (where ampy = 2-(aminomethyl)pyridine), in which the terpy chelate labilizes the metal center, are able to catalyze the conversion of NAD+ to 1,4-NADH using sodium formate as a source of hydride. We showed that this complex can control the [NAD+]/[NADH] ratio and potentially induce reductive stress in living cells, which is accepted as an effective method to kill cancer cells. Polypyridyl Ru(II) complexes, characterized in terms of the behavior in aqueous solutions, can be used as model systems to monitor heterogeneous multiphase ligand substitution reactions at the solid-liquid interface. Colloidal coordination compounds in the submicron range were synthesized from Ru(II)-aqua derivatives of starting chlorido complexes via the anti-solvent procedure and stabilized by a surfactant shell layer.

Influence of Number of Ligands and Point Group on the Electronic Structure of Co2+ Aqua-Complexes

The nucleation process of zeolitic imidazolate frameworks (ZIFs) is, to date, not yet completely understood, making the search for tailored materials very difficult. Recently, it has been shown that, during the formation process, the symmetry of the precursors is reduced by ligand elimination and substitution reactions. The octahedral precursors with simple ligands, such as water, methanol, and/or NO3-, are transformed to five- and finally four-coordinated complexes with imidazole ligands. This reduction of symmetry, caused both by the changing coordination environment and distortions from the perfect symmetry leading to another point group, will have a large influence on the electronic structure and more specifically on the d-orbital splitting. This, in turn, will affect the d-d electronic excitations, which can be followed using UV-vis spectroscopy and which can help to unravel the formation process. In this work, we systematically investigate how the lowering of the number of ligands affects the symmetry and thus the geometry and electronic structure of Co2+ complexes with six, five, and four aqua ligands. Therefore, we first resort to qualitative techniques, such as crystal field theory (CFT) and ligand field theory (LFT), which reveal that the orbital splitting is characteristic for the number of ligands. However, as these techniques are not capable of providing quantitative results without the use of experimental data as input, we perform various computational calculations. Both average of configuration (AOC) and unrestricted density functional theory (UDFT) are thoroughly investigated, and we will determine which technique is the best suited to properly describe the ground state of these systems. To investigate the dependency on the d-orbital occupation, we also investigated V2+, Mn2+, and Ni2+ hexa-aqua-complexes and compared them to the Co systems.

Conformation, hydration, and ligand exchange process of ruthenium nitrosyl complexes in aqueous solution: Free-energy calculations by a combination of molecular-orbital theories and different solvent models.

Distribution of solvent molecules near transition-metal complex is key information to comprehend the functionality, reactivity, and so forth. However, polarizable continuum solvent models still are the standard and conventional partner of molecular-orbital (MO) calculations in the solution system including transition-metal complex. In this study, we investigate the conformation, hydration, and ligand substitution reaction between NO2 - and H2 O in aqueous solution for [Ru(NO)(OH)(NO2 )4 ]2- (A), [Ru(NO)(OH)(NO2 )3 (ONO)]2- (B), and [Ru(NO)(OH)(NO2 )3 (H2 O)]- (C) using a combination method of MO theories and a state-of-the-art molecular solvation technique (NI-MC-MOZ-SCF). A dominant species is found in the complex B conformers and, as expected, different between the solvent models, which reveals that molecular solvation beyond continuum media treatment are required for a reliable description of solvation near transition-metal complex. In the stability constant evaluation of ligand substitution reaction, an assumption that considers the direct association between the dissociated NO2 - and complex C is useful to obtain a reliable stability constant.

Development of a colorimetric assay for quantification of favipiravir in human serum using ferrihydrite

We developed a colorimetric analytical method for favipiravir (FPV), a promising treatment for COVID-19. FPV forms yellow complexes with ferrihydrite (Fh) by a ligand substitution reaction with the iron (III) hydroxyl surface groups in Fh. Fh-coated microbeads were packed into a capillary tube with an inner diameter of 1 mm. FPV-spiked serum after pretreatment was drawn into the capillary packed with Fh-coated microbeads. The intensities of the yellow-color complexes on the microbeads were transformed into red-green-blue (RGB) pixels using Image-J software 1.8, and the difference between green and blue was used as the analytical signal. The signal increased with increasing FPV concentration. The proposed method showed good linearity (R2 = 0.9907) over a concentration range of 25–200 μg/mL. The RSD (n = 3) and the LOD (3σ) values were estimated to be 2.8–15.4% and 16.91 μg/mL, respectively. The proposed method enables us to quantify FPV rapidly and easily without the need for expensive equipment.

Researches on Photofunctional and Photocatalytic Chemistry of Metal Complexes as Core Materials

We found the following new photochemical reactions and photophysical properties of transition metal complexes: (1) photochemical formation of Ru(II) hydride complexes, (2) photochemical ligand substitution reactions of the Re(I)diiminetricarbonyl complexes, and (3) control of photophysical and electrochemical properties of metal complexes by introducing p-p interaction between ligands. Application of these reactions and photophysical properties of transition metal complexes enabled us to synthesize new photofunctional metal-complex oligomers and polymers， and to develop efficient， durable， and highly selective photocatalysts for hydride reduction of NAD(P)+ models and CO2 reduction. We also succeeded construction of new photofunctional hybrids of the metal-complex photocatalysts with various solid materials， i.e. semiconductor-particle photocatalysts， p-type semiconductor electrodes， and mesoporous organosilica， which can drive photocatalytic reduction of CO2 via Z-scheme electron transfer， photocatalytic CO2 reduction by using water as a reductant and visible light as energy， and lightenergy accumulation for photocatalytic CO2 reduction， respectively.

En route from metal alkoxides to metal oxides: metal oxo/alkoxo clusters

Molecular metal oxo or oxo/alkoxo clusters, MwOx(OH/OR)y(L/X)z (L or X = organic ligands), can often be isolated upon (partial) hydrolysis of metal alkoxides. Investigation of such clusters leads to a better understanding of the basic processes of sol–gel chemistry. The ligands not only stabilize the cluster core but also influence to some extent the cluster structures. They can easily change their position on the cluster surface, thus adapting to changing cluster geometries, and can be exchanged under certain conditions. A close inspection of titanium oxo/alkoxo cluster structures, taken as an informative example, shows that Ti3O units (with or without organic ligands) are the basic building blocks. Clusters with higher nuclearities appear to be predominantly formed by cluster–cluster or by cluster–monomer condensations. Ligand substitution or condensation reactions within a cluster unit are also possible.Instead of extended metal oxide networks, metal oxo/alkoxo clusters may be formed upon hydrolysis of metal alkoxides.

Ab initio metadynamics simulations on the formation of calcium silicate aqua complexes prior to the nuleation of calcium silicate hydrate

Although the calcium silicate hydrate (C-S-H) has been used for millennium, the structure and formation of C-S-H are still unclear at atomistic level. In this work, we find two kinds of calcium silicate aqua complexes, [Ca(H2O)n(SiO2(OH)2)] and [Ca(H2O)n(SiO(OH)3)]+, prior to the nuleation of C-S-H. The ab initio metadynamics simulations show that [Ca(H2O)n(SiO2(OH)2)] and [Ca(H2O)n(SiO(OH)3)]+ have six and five stable states on the free energy surface (FES), respectively. There are different ligand substitution mechanisms between the FES minima. The four- and six- coordinated [Ca(H2O)n(SiO2(OH)2)] only follow associative and dissociative mechanisms, respectively. While both dissociative and associative mechanisms apply to the six-coordinated [Ca(H2O)n(SiO(OH)3)]+ and no four-coordinated ligand substitution reaction is found. The most stable states in both systems show a distorted CaO octahedral feature. Our findings may promote a fundamental understanding for the calcium silicate based species in solution and pre-nucleation process of C-S-H.

Ruthenium tris(σ-B-H) borate complexes: synthesis, structure, and reactivity.

The coordination of the B-H bond to a transition metal is fundamentally intriguing due to its connection with the transition metal-mediated B-H bond activation mechanism and catalysis. Most of the reported examples are σ-borane/borate complexes containing one or two σ-B-H bonds. However, examples of compounds containing three σ-B-H bonds are still much rarer. Herein, we report a facile approach for the synthesis of rare transition metal tris(σ-B-H) borate complexes by the salt elimination protocol using [Cp*RuCl]4 and lithium trihydroborates Li[ArBH3] containing 2,6-disubstituted aryl groups. These complexes have remarkable thermal stability in solution. In addition, this novel class of compounds has the unusual σ-complex that features three labile σ-B-H bonds. Our studies on these new species demonstrate that the coordination σ-B-H bond can undergo H/D exchange with D2 and ligand substitution reactions with PPh3, PCy3 and IPr2Me2. These results provide new approaches for the synthesis of both tris(σ-B-H) borates and bis(σ-B-H) borates.

Trinuclear ReFePt clusters with a μ3-phenylvinylidene ligand: synthetic approaches, rearrangement of vinylidene, and redox-induced transformations.

A series of trinuclear μ3-vinylidene ReFePt clusters were synthesized by the application of two approaches: (i) reactions of the binuclear RePt μ-vinylidene complexes with Fe2(CO)9; (ii) ligand substitution or exchange reactions at the Pt atom in the synthesized ReFePt clusters. The molecular structures of CpReFePt(μ3-CCHPh)(CO)5[P(OEt)3]L [L = CO; P(OEt)3] were determined by an X-ray diffraction study. The obtained compounds were studied by IR and 1H, 13C and 31P NMR spectroscopy. The spectroscopic study revealed that the clusters CpReFePt(μ3-CCHPh)(CO)5[P(OEt)3]L [L = CO; P(OEt)3] and CpReFePt(μ3-CCHPh)(CO)6[P(OPri)3] undergo isomerization upon dissolution, resulting in three isomers with different positions of the μ3-vinylidene ligand over the ReFePt core. The redox properties of the clusters were studied by electrochemical methods. The relatively stable cation-radicals obtained by chemical oxidation of CpReFePt(μ3-CCHPh)(CO)6[P(OPri)3] and CpReFePt(μ3-CCHPh)(CO)5[P(OEt)3]2 with ferrocenium tetrafluoroborate were characterized by EPR spectroscopy.

Photo-induced ligand substitution of Cr(CO)6 in 1-pentanol probed by time resolved X-ray absorption spectroscopy.

Cr(CO)6 was investigated by X-ray absorption spectroscopy. The spectral signature at the metal edge provides information about the back-bonding of the metal in this class of complexes. Among the processes it participates in is ligand substitution in which a carbonyl ligand is ejected through excitation to a metal to ligand charge transfer (MLCT) band. The unsaturated carbonyl Cr(CO)5 is stabilized by solution media in square pyramidal geometry and further reacts with the solvent. Multi-site-specific probing after photoexcitation was used to investigate the ligand substitution photoreaction process which is a common first step in catalytic processes involving metal carbonyls. The data were analysed with the aid of TD-DFT computations for different models of photoproducts and signatures for ligand rearrangement after substitution were found. The rearrangement was found to occur in about 790 ps in agreement with former studies of the photoreaction.

1,1′‐Ferrocenylene‐Bridged Bis(N‐Heterocyclic Olefin) Derivatives

AbstractThe 1,1′‐ferrocenylene (fc)‐bridged bis(N‐heterocyclic olefin) compounds (IMes=CH)2fc (1, IMes=1,3‐dimesitylimidazolin‐2‐ylidene) and (IPr=CH)2fc (2, IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazolin‐2‐ylidene) were synthesised from (ICH2)2fc (3) and the respective N‐heterocyclic carbene IMes or IPr. Ligand substitution reactions of 1 and 2 with [BH3(THF)] afforded the complexes [1(BH3)2] and [2(BH3)2] as mixtures of the rac‐ and meso‐diastereomers. The new ferrocene derivatives 1–3 and the complexes meso‐[1(BH3)2], rac‐[1(BH3)2] and rac‐[2(BH3)2] were structurally characterised by single‐crystal X‐ray diffraction. 1 and 2 represent a new class of ferrocene‐based, and hence redox‐active, bidentate ligands. The presence of three redox‐active moieties, viz. the ferrocene unit and the two NHO units, is reflected by three consecutive oxidations according to an electrochemical investigation exemplarily performed with 2 by cyclic voltammetry.