Gold Complexes Research Articles

Harnessing Organometallic Gold(III) Complexes as Precision Scaffolds for Next-Generation Therapeutic and Imaging Agents.

Gold(III) organometallic complexes, particularly cyclometalated Au(III) compounds, have emerged as powerful tools in catalysis and bioinorganic chemistry, offering unique reactivity distinct from their Au(I) counterparts. Among their most interesting transformations, C-S cross-coupling reactions have become a selective strategy for cysteine arylation, enabling site-specific modifications of peptides and proteins. This review provides a comprehensive overview of cyclometalated Au(III) complexes in C-S bond formation, detailing the mechanistic insights, ligand effects, and electronic factors that dictate their reactivity. The role of ancillary ligands in tuning stability and selectivity is critically assessed, alongside advancements in structural modifications that enhance catalytic efficiency. Beyond fundamental C-S cross-coupling, we explore the broader applications of these gold(III) complexes, including enzyme inhibition, metabolic disruption, and transmembrane protein modulation, with implications in anticancer therapy, antimicrobial strategies, andin vivocatalytic transformations. By bridging fundamental organometallic reactivity with innovative biomedical applications, this review highlights the potential of cyclometalated Au(III) complexes as next-generation catalysts for both synthetic and therapeutic innovations.

Gold Acyclic Diaminocarbene Complexes as Selective and Potent Agents for Multitarget Cancer Therapy.

Gold acyclic diaminocarbene (ADC) complexes represent a promising, yet underexplored, class of chemotherapeutics. ADCs offer superior flexibility and stronger sigma donation compared with traditional N-heterocyclic carbenes, making them ideal ligands for stable gold-based drugs. In this study, a series of gold ADC complexes were synthesized via the nucleophilic addition of amines to [AuCl(CNCy)], yielding three structural families: gold-chloride-ADC (chiral and achiral), bis(carbene), and thiolate-gold-ADC complexes. Extensive characterization, including X-ray diffraction, revealed noncovalent interactions, such as hydrogen bonding and aurophilic contacts, that significantly shape their molecular architecture. These complexes exhibit potent cytotoxicity (IC50 in submicromolar) against drug-resistant cancer cell lines (A549, HCT116 WT, Jurkat, MiaPaca2), with some showing high selectivity toward cancer cells over healthy lymphocytes (selectivity index up to 74). Mechanistic investigations indicate that they disrupt mitochondrial function, elevate reactive oxygen species (ROS), and, in the case of bis(carbene) species, bind DNA. Apoptosis is induced at low concentrations, while higher doses trigger alternative death pathways. Notably, they also strongly inhibit thioredoxin reductase (TrxR), comparable in potency to auranofin. The combination of ROS induction, DNA interaction, mitochondrial disruption, and TrxR inhibition highlights the multitargeted anticancer potential of gold-ADC complexes and supports their further development as selective and effective chemotherapeutic agents.

Is the Trans-Influence the Same Quantitative Effect of Two Metal-Ligand Bonds on the Strength of Each Other?

ABSTRACT Herein, we want to show that the value of the intrinsic trans-influence of two trans ligands, can be calculated on the basis of the concept of the cooperativity of bonds. Two types of trans-influence, including a “quantitative trans-influence” (QTI) and a “relative trans-influence” (RTI) were defined for two trans ligands in one metal complex. Then the trans-influence was evaluated in a series of gold(I) complexes of the type [LAuCO]+/0, and also several square planar complexes of the type [LPtCl3]–/0. Four types of quantitative trans-influence were calculated as QT I ν , QT I d , QT I BDE and QT I IE based on the quantitative impact of a ligand on the value of vibrational stretching frequency, bond distance, bond dissociation energy, and interaction energy, respectively, of a metal-ligand bond trans to it. Interestingly, the QT I BDE and QT I IE values for the CO molecule in [LAuCO]+/0 complexes, and those for Cl– anion in [LPtCl3]–/0 complexes, are always equal to those of the corresponding trans ligand L. However, in each metal complex, the relative trans-influence of two trans ligands can be quite different.

Contrasting Solution and Gas‐Phase: Understanding Structure and Reactivity of Gold‐Diazenyl Intermediates

Gold(I)‐catalyzed cross‐coupling reactions with aryldiazonium salts are instrumental in forming C‐C and C‐N bonds. However, mechanistic details remain unclear, particularly the role of diazenyl intermediates. We employ stoichiometric reactions, NMR spectroscopy, electrospray ionization mass spectrometry, and infrared photodissociation spectroscopy to investigate the reactivity of gold‐aryl complexes with aryldiazenyl radicals and aryldiazonium ions. Our results reveal that [(NHC)Au(Ar)] complexes form short‐lived Electron Donor‐Acceptor (EDA) complexes [(NHC)Au(Ar)(Ar’N2)]+ in solution, which undergo a C‐N coupling reaction during the transfer to the gas phase to form gold(I) azoarene complexes. The rearrangements of the gold complexes during the transfer from the solution to the gas phase were studied by ion‐mobility separation, IRPD spectra, and delayed reactant labeling experiments. We also show that gold‐chloride complexes facilitate the oxidative addition of aryldiazonium ions to form [(NHC)AuIII(Cl)(Ar)(N2)]+, suggesting an alternative non‐radical mechanism initiating the C‐C bond formation reactions. In solution‐phase reactivity, ligand steric effects are crucial in steering the reaction selectivity: IMes ligands favor N2 expulsion followed by the C‐C coupling, while bulkier IPr and IPent ligands promote the C‐N coupling. These findings refine our understanding of gold(I)‐mediated cross‐coupling reactions, and the observed solution‐gas phase discrepancies highlight the need for careful interpretation of ESI‐MS data in mechanistic studies.

DNA and gold(III) complexes with nitrogen-containing ligands

DNA and gold(III) complexes with nitrogen-containing ligands

A Molecular Planetarium: Evidence for an Iodide Ligand Orbiting Two Gold(I) Ions in the Luminescent Cation, [Au2(μ-1,2-Bis(diphenylphosphino)methane)2I

Four new crystalline gold(I) complexes, [Au2(μ-dppm)2I][Au2(μ-dppm)2(μ-I)](AsF6)4·4CH2Cl2 (1), [Au2(μ-dppm)2(μ-I)]I·2CH2Cl2 (2), [Au2(μ-dppm)2(μ-I)](PF6)·CH2Cl2 (3), and [Au2(μ-dppm)2](AsF6)2·CH2Cl2 (4) where dppm is bis(diphenylphosphino)methane) have been prepared and structurally characterized by single crystal X-ray diffraction and nuclear magnetic resonance spectroscopy (NMR). Yellow crystals of [Au2(μ-dppm)2(μ-I)]I·2CH2Cl2 (2) and [Au2(μ-dppm)2(μ-I)](PF6)·CH2Cl2 (3) have a structure with two three-coordinate gold(I) ions held in close proximity by the dppm and bridging iodide ligands. Crystals of [Au2(μ-dppm)2I][Au2(μ-dppm)2(μ-I)](AsF6)4·4CH2Cl2 (1) have two different cations: one similar to complexes 2 and 3 and the other cation with a terminal iodide ligand in an unusual arrangement that binds a two-coordinate gold(I) ion to a three-coordinate gold(I) ion through an aurophilic interaction. In contrast, [Au2(μ-dppm)2](AsF6)2·CH2Cl2 (4) has no anion bound and only has the gold ions as two-coordinate centers. Each complex displays luminescence under UV irradiation in the solid and solution states. Remarkably, the NMR spectra of solutions of the iodide complexes (1), (2), and (3) suggest that the iodide ion is bound to the [Au2(μ-dppm)2]2+ core but is able to circulate around this core.

Homogeneous Gold Catalysis: Development and Recent Advances.

Gold catalysis has witnessed remarkable advances over the past decade, with numerous insightful reviews chronicling this progress. However, a comprehensive review addressing developments in the field during the post-pandemic COVID era remains notably absent. This review aims to bridge that gap by providing an in-depth analysis of recent studies, shedding light on the unique properties of gold complexes, particularly the intriguing aurophilic interactions that distinguish gold chemistry. The review systematically explores the latest achievements in both mono- and dinuclear gold-catalyzed reactions, with a focus on their applications in diverse fields, including redox coupling, asymmetric catalysis, photo-, and electrocatalysis. A special emphasis is placed on the comparative performance of mono- and dinuclear gold catalysts, with the latter often exhibiting enhanced catalytic efficiency and selectivity in certain reactions. By integrating mechanistic insights and DFT perspectives with representative experimental studies from recent years, this review highlights the significance of gold catalysis to synthetic chemistry, identifies emerging trends and outlines future directions for the field.

The Metallic Edge: Organometallic Compounds As Anticancer Drugs

The study of organometallic compounds as an Anti-Cancer Agents has been focused due to their versatility in various physical and chemical properties. However any attempt to understand how organometallic compounds act as anti-cancer agents i.e. their attacking mechanisms ,site of attack and also the various types of organometallic compounds exhibiting cytotoxicity against cancer cells approaches initially to activation of complexes. This dissertation discovers the aspects of the chemistry related to many types of organometallic compounds such as Metallocenes (including derivatives of ferrocenes, vanadocenes and zirconocene), Metal-Arenes(ruthenium arenes, gold complexes and osmium arenes). All these organometallic derivatives are a part of recent researches and their physical and chemical properties along with their cytotoxicity have been detected in detail. Therefore the ideas for enhancing the cytotoxicity of these complexes had also came in idea i.e. by combining a pharmacophore like that in case of osmium complexes according to the latest researches ,as compared to the monodentate ligand, Os(II) arene complexes with specific phenylazopyridine ligands (π-acceptor ligands) were more powerful and unreactive with iodide. They are active in vivo and 49 times more effective on average in a Sanger panel of 809 cancer cell lines than cisplatin. The evolution of chemical properties of organometallic complexes and their studies over the years progressively developed. Although previous research on the biological effects of cisplatin and the emergence of cisplatin resistance phenotypes provide critical information that can be used to produce platinum and non-platinum metal-based medicines for cancer therapy that are more effective and less harmful. It is to be predicted that non-platinum metal compounds may have toxic side effects and anti-cancer efficacy that are notably different from those of platinum-based medications.

Gold nanoparticle resveratrol complex increases apoptosis in KRAS mutant pancreatic cancer cells

The KRAS G12D mutation is the most prevalent type of pancreatic cancer and is found in about 35% of patients. Numerous natural chemicals are frequently investigated in cancer treatment to decrease side effects. Resveratrol (RVT) is a polyphenol that can promote cancer cell apoptosis and improve chemotherapy efficacy in cancers. To enhance delivery rate and efficacy, the size of about 30 nm gold nanoparticles (GNPs) was synthesized and conjugated to resveratrol via polyvinylpyrrolidone (GRs) for high bioavailability. Compared to RVT and GNPs, GRs had less inflammatory response and less toxicity on RAW 264.7 cells. This suggests that the toxicity of resveratrol can be alleviated by conjugation with gold nanoparticles. The viability of the human pancreatic cancer cell line (AsPC-1) decreased in sequence of GRs > RVT > GNPs, suggesting an enhanced anticancer effect of the GRs compared to resveratrol (RVT) alone. In addition, the extent of apoptosis was much bigger with GRs compared to RVT and GNPs. The apoptotic effects were confirmed with cell cycle arrest and expression of apoptosis-related genes and proteins. Thus, GRs had a better extent of anticancer effect than RVT, suggesting that GRs be considered as one of the prospective anti-cancer drugs for pancreatic cancer treatment.

A Cytotoxic Indazole-based Gold(III) Carboxamide Pincer Complex Targeting DNA Through Dual Binding Modes of Groove Binding and Alkylation.

Gold(III) complexes have garnered increasing attention in drug delivery due to their structural and mechanistic similarities to cisplatin. This study investigates an indazole-based gold(III) carboxamide pincer complex, [N2·N6-bis(1-methyl-1H-indazol-3-yl)pyridine-2·6-dicarboxamide]gold(III) chloride (AuL), for its potential as an anticancer agent. Speciation analysis at physiological pH revealed that AuL predominantly exists as a neutral chlorinated species. The complex exhibited strong cytotoxicity against the MCF-7 breast cancer cell line, with an impressive IC50 value of 9µM, while showing no significant activity against the HT-29 colon cancer cell line. Comprehensive analysis using electrophoresis, viscometry, ultraviolet-visible spectroscopy (UV-Vis), circular dichroism (CD), linear dichroism (LD) spectroscopy, and biomolecular simulations demonstrated that AuL binds to DNA via a dual mechanism, specifically minor groove binding and alkylation, with binding constants Ka1 = 1.48 × 109 M-1 and Ka2 = 6.59 × 105 M-1, respectively. Our data indicate that AuL initially binds to the minor groove of DNA, at which point a nucleobase substitutes the Cl ion, resulting in AuL binding directly to the DNA bases. In conclusion, the dual binding mode of AuL with DNA underscores its potential as a promising anticancer agent, opening new avenues for drug discovery and the development of metal-based therapeutics.

IPr*diNHC: Sterically Adaptable Dinuclear N-Heterocyclic Carbenes.

N-Heterocyclic carbenes (NHCs) have been established as the predominant ligand class in inorganic and organometallic chemistry. Simultaneously, there has been a major interest in dinuclear ligands, where cooperative effects between the metal centers have been widely exploited across numerous research avenues. Herein, we report the synthesis of dinuclear sterically hindered and adaptable N-heterocyclic ligands based on the modular IPr* framework. These ligands are distinguished by (1) the bridging group between the N-heterocyclic carbene donors and (2) the steric and electronic characteristics of the N-aromatic wingtips. The net effect is a remarkably broadly ranging steric environment around the metal center (%Vbur of 33.9 up to 60.4%) as well as versatile conformation ranging from the perfectly linear (3.2°) to almost fully perpendicular (79.3°) between the carbene donors. The ligands have been evaluated in the gold(I)-catalyzed hydration and carboxylation of alkynes, where they show enhanced catalytic reactivity over mononuclear gold(I) complexes. Considering the importance of dinuclear N-heterocyclic carbenes across different research fields, we expect that this ligand class will be of broad interest in inorganic and organometallic chemistry.

C‐Scorpionate Gold(III) Catalysts in Nitroarene Reduction: A Novel Strategy

AbstractThe reduction of nitroarenes is of great interest in both industrial and environmental contexts. These compounds are essential in various synthetic processes, yet their release into the environment poses significant risks to both ecosystems and human health. Thus, developing efficient, selective, and environmentally friendly catalytic processes for nitroarene reduction is crucial for sustainable chemical manufacturing. This work explores the effect of catalysts, solvents, and reducing agents on the reaction kinetics of nitroarenes reduction. For the first time, C‐scorpionate complexes are used as catalysts for this reaction: gold(III) complexes bearing different C‐scorpionate ligands [AuCl2(κ2‐RCpz3)]n+ (pz = pyrazol‐1‐yl, R = SO3− (1), n = 0; R = H (2) or CH2OH (3), n = 1) were applied as catalysts under very mild reaction conditions, evaluating their efficiency and stability. Complexes 1 and 3 exhibited outstanding catalytic performance, achieving near complete nitroarene reduction in ca. 5 min of reaction. Solvent–catalyst interactions appear to affect significantly their catalytic activity. A wide range of substituted nitroarenes was successfully reduced with high efficiency, demonstrating the broad applicability of the catalysts. The findings highlight the potential of these ambient water‐prepared C‐scorpionate gold(III) complexes as highly effective catalysts for fast reduction of nitroarene.

Aqueous-Phase Synthesis of Cyclic Trinuclear Cluster-Based Metal-Organic Frameworks.

The synthesis of metal-organic frameworks (MOFs) often involves high-boiling-point organic solvents, which can have extensive environmental impact and limit their large-scale applications. Here, we present a one-pot aqueous-phase approach for the rapid preparation of 33 trinuclear-copper-cluster-based MOFs (1 to 33) with different pyrazoles under ultrasonic irradiation. To address the water-solubility challenge of organic linkers, we employ aromatic amines/aldehydes and pyrazole aldehydes/amines to in situ generate imine-based pyrazoles. This linker dismantling strategy enables the formation of low-concentration pyrazoles, which are essential for the assembly of trinuclear-copper-cluster-based MOFs in the aqueous phase. The use of preassembled trinuclear gold complexes instead of aromatic amines affords an Au-Cu-based MOF (34) of alternating gold and copper clusters, a rare example of MOFs with mixed yet precise arrangement of metal compositions. Additionally, the direct addition of pyruvic acid to the reaction mixture results in the facile synthesis of a carboxylic-acid-functionalized MOF (35), eliminating the need for preinstallation or postmodification steps in traditional MOF synthesis. Furthermore, we demonstrate 11-AA as an efficient photocatalyst for cross-dehydrogenative coupling (CDC) reactions, exploiting the synergetic effect of substrate activation on the copper sites and subsequent coupling initiated by the photosensitive organic linkers. This work offers a simple solution for making MOFs with minimal environmental impact; it also opens up possibilities for developing multifunctional MOFs for diverse applications.

Divergent One‐Pot Two‐Step Synthesis of Phosphoryl‐Substituted 4‐Quinolones and 3‐Indolinones

Herein, an approach is developed for the selective two‐step synthesis of phosphoryl‐substituted 4‐quinolones and phosphoryl‐substituted 3‐indolinones. This is achieved through the reaction of (3‐(2‐iodoaryl)‐3‐oxoprop‐1‐yn‐1‐yl)phosphonates with anilines followed by Cu‐catalyzed intramolecular cyclization of the intermediately formed regioisomeric enamines, which are selectively formed under neat conditions or in the presence of a gold complex as a catalyst. This method allows for the synthesis of a series of phosphoryl‐substituted 4‐quinolones and phosphoryl‐substituted 3‐indolinones in good yields.

Gold(III) Complexes with 2-(1-Ethylbenzyl)pyridine as Promising Antimicrobial and Antitumor Agents.

Antimicrobial resistance (AMR) is one of the most urgent public health problems worldwide; multidrug resistance (MDR) is also of concern. In an effort to find new classes of antibiotics, recent studies have found that coordination compounds of noble metals show promising biological effects both in vitro and in vivo, deserving attention as a new class of possible antimicrobial agents. Metal ions in biological systems can essentially have two roles: structural or functional. In the former, the metal ion serves to stabilize structures, especially proteins, while in the latter, the metal is involved in bio-site reactivity (essentially in metallo-enzymes). Two new complexes with 2-(1-ethyl-benzyl)pyridine (pyeb), one monodentate adduct and one cyclometalated ([Au(pyeb)Cl3] and [Au(pyeb-H)Cl2], respectively), have been synthesized, characterized, and tested against Gram-positive and Gram-negative bacteria, as well as yeasts, revealing promising antibacterial and antibiofilm properties. The two complexes have been thoroughly characterized by means of 1D and 2D NMR spectroscopy, as well as by cyclic voltammetry, conductivity measurements, FT-IR, and elemental analysis. The study showed that the two derivatives are structurally and chemically different, with the cyclometalated complex being chemically and electrochemically more stable. Antimicrobial assays demonstrated that solutions of the monodentate adduct and of the cyclometalated complex have inhibitory and antibiofilm effects against the pathogenic bacteria E. coli, K. pneumoniae, S. aureus, and S. pyogenes but were unable to reveal a fungicidal effect on C. albicans. A preliminary study was conducted to assess the anti-cancer activity of the compounds, and treatments with the gold compounds also resulted in a significant reduction in the metabolic activity of HT29 colon cancer cells.

Benzothiazolin-2-ylidene gold(I) complexes as precursors for gold nanoparticles

Benzothiazolin-2-ylidene gold(I) complexes as precursors for gold nanoparticles

Current state of the art of gold complexes as antileishmanial agents

Current state of the art of gold complexes as antileishmanial agents

Motivation on Intramolecular Through-Space Charge Transfer for the Realization of Thermally Activated Delayed Fluorescence (TADF)-Thermally Stimulated Delayed Phosphorescence (TSDP) in C^C^N Gold(III) Complexes and Their Applications in Organic Light-Emitting Devices.

Thermally activated delayed fluorescence (TADF) and the very recently established thermally stimulated delayed phosphorescence (TSDP) are two promising approaches for enhancing the performance of organic light-emitting devices (OLEDs). Here, we have developed a new class of through-space charge transfer (TSCT) carbazolylgold(III) C^C^N complexes with unique TADF-TSDP properties by introducing a rigid arylamine on the carbazolyl auxiliary ligand. The highly twisted conformation between the C^C^N and carbazolyl ligands induces strong through-bond ligand-to-ligand charge transfer (TB-LLCT) character in their lowest singlet and triplet excited states, with small singlet-triplet energy gaps for efficient TADF. Moreover, the close spatial proximity between the cyclometalating ligand and the lateral arylamine enables appreciable intramolecular through-space electronic coupling that allows the generation of relatively low-lying triplet through-space ligand-to-ligand charge transfer (3TS-LLCT) excited states. The TADF-TSDP properties are verified by temperature-dependent emission, lifetimes, and ultrafast transient absorption studies. Interestingly, through better alignment with extended planarity and the strengthening of the electron-donating ability of the lateral arylamine, the enhanced through-space electronic coupling can effectively perturb the energies of 3TBCT, 3TSCT, and intraligand (3IL) excited states and thus manipulates the TSDP efficiency. Orange-emitting vacuum-deposited OLEDs made with these gold(III) complexes demonstrate respectable maximum external quantum efficiencies of >10% and long operational half-lifetimes of up to 65,314 h at a luminance of 100 cd m-2. This work not only demonstrates the realization of interesting TADF-TSDP and TSCT properties in the gold(III) C^C^N cyclometalated system but also enriches the diversity of molecular design for high-performance TSDP and TSCT emitters.

Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells

AbstractWe present a comprehensive study on the chemical reactivity in the gas phase, with amino acids and peptides, and in the cell, the anticancer activity and localization of a series of seven cationic biphenyl gold(III) complexes with aryl, alkyl, and chiral diphosphine ancillary ligands. Despite some structural differences, all the complexes similarly featured high stability toward reduction or ligand exchange in cell‐free conditions. The biphenyl Au(III) complex including the 1,2‐diphenylphosphinoethane (dppe) ligand manifested the same high stability in a cellular setting, as attested by a combination of cryo‐Synchrotron Radiation‐X‐Ray Fluorescence (cryo‐SR‐XRF) nano‐imaging and cryo‐Synchrotron Radiation‐X‐ray Absorption Spectroscopy (cryo‐SR‐XAS) measurements. Tandem cryo‐SR‐XRF elemental mapping and confocal fluorescence microscopy demonstrated the selective accumulation of the dppe complex in mitochondria. This represents the first study of the speciation and distribution of an organogold(III) complex in cancer cells.

Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells.

We present a comprehensive study on the chemical reactivity in the gas phase, with amino acids and peptides, and in the cell, the anticancer activity and localization of a series of seven cationic biphenyl gold(III) complexes with aryl, alkyl, and chiral diphosphine ancillary ligands. Despite some structural differences, all the complexes similarly featured high stability toward reduction or ligand exchange in cell-free conditions. The biphenyl Au(III) complex including the 1,2-diphenylphosphinoethane (dppe) ligand manifested the same high stability in a cellular setting, as attested by a combination of cryo-Synchrotron Radiation-X-Ray Fluorescence (cryo-SR-XRF) nano-imaging and cryo-Synchrotron Radiation-X-ray Absorption Spectroscopy (cryo-SR-XAS) measurements. Tandem cryo-SR-XRF elemental mapping and confocal fluorescence microscopy demonstrated the selective accumulation of the dppe complex in mitochondria. This represents the first study of the speciation and distribution of an organogold(III) complex in cancer cells.