Gold Complexes Research Articles

Abstract A013: Auranofin induces lethality driven by reactive oxygen species in high-grade serous ovarian cancer cells

Abstract High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer cases in the clinical setting; the survival rate for this disease remains remarkably low due to the lack of a long-term consolidation therapy following standard platinum-based chemotherapy. There is minimal improvement in the survival rate of this disease due to the development of resistance to platinum drugs as the disease recurs. The purpose of this study was to develop a novel treatment modality against HGSOC using the gold complex auranofin (AF). AF primarily functions as a pro-oxidant agent through the inhibition of thioredoxin reductase (TrxR), an antioxidant enzyme that is overexpressed in ovarian cancer. We explored the effect of AF on TrxR activity and various mechanisms of cytotoxicity using HGSOC cells that are clinically sensitive (PEO1) or resistant (PEO4) to platinum. We treated PEO1 cells and PEO4 cells with AF for 72 hours and analyzed its short-term toxicity by assessing cell viability and DNA content by flow cytometry, and the long-term anti-proliferative capacity using colony formation assays. We also assessed the mechanisms of cell death induced by AF including the activation of mechanisms of apoptosis, activation of executor caspases -3 and -7, cleavage of poly-(ADP-ribose) polymerase (PARP), changes in the mitochondrial membrane potential (MMP), and DNA damage. In addition, we studied the interaction between AF and another pro-oxidant, L-buthionine sulfoximine (L-BSO), an anti-glutathione (GSH) agent. We demonstrate that AF potently inhibits the activity of TrxR at non-cytotoxic concentrations while reducing the viability of HGSOC cells regardless of their sensitivities to platinum. We showed that AF induces accumulation of reactive oxygen species (ROS), triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis. AF-induced cell death and morphological effects were abrogated by the ROS scavenger, N-acetyl cysteine (NAC). In addition, the lethality of AF in HGSOC was associated with the activation of caspase-3/7, cleavage of PARP, and the generation of DNA damage, effects that were prevented by the ROS scavenger NAC. Finally, when AF and L-BSO were combined, we observed a synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS with a decrease in the antioxidant, GSH. In summary, our results support the concept that AF can be used alone to kill HGSOC cells by causing ROS-mediated apoptosis. Furthermore, we demonstrate that a large depletion of antioxidants caused by combining AF and L-BSO is highly efficient in synergistically killing HGSOC cells. These findings suggest that the combination of AF and L-BSO is a potential option to develop a consolidation therapy against HGSOC, which can overcome the problem of platinum resistance during recurrent stages of the disease. Citation Format: Farah H. Abdalbari, Elvis M. Jaramillo, Benjamin N. Forgie, Estelle Tran, Alicia A. Goyeneche, Carlos M. Telleria. Auranofin induces lethality driven by reactive oxygen species in high-grade serous ovarian cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A013.

Perhalophenyl–Phosphide: A Couple Needed to Stabilize Phosphide–Gold Complexes

The synthesis of gold(III) and gold(I)–gold(III) complexes with phosphide bridges is still a matter that requires solutions for their marked instability, in spite of the affinity of this metal in both oxidation states for phosphorous donor ligands. In the course of our studies, we realized that the presence of perhalophenyl groups of the type pentafluorophenyl or 3,5-dichlorotrifluorophenyl in the complexes gives rise to an increase in their stability that eases their isolation and structural characterization. In this paper, we describe two new fully characterized neutral compounds of this type to extend the knowledge on this family of compounds, [{Au(C6Cl2F3)2}2(µ-PPh2)2] (1) and [{Au(C6Cl2F3)2(µ-PPh2)2Au}2] (2). In this work, we analyze the role of the perhalophenyl groups in the stability of these complexes by using quantum chemical topology methodologies, specifically employing an analysis of the non-covalent interactions (NCIs) in real space and evaluating the electrostatic potential surfaces (ESP). Our findings reveal the existence of appreciable π-stacking interactions among the perhalophenyl and phenyl groups in both compounds, significantly contributing to the stability of the systems.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. The IC50 values for PBTDG and sorafenib were found to be 1.48 μM and 4.45 μM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 μM, 3 μM, and 10 μM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 μM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 μM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents

Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [Au(dpta)Cl2, Au(dpta)(mrdtc), and Au(dpta)(dedtc)] or thiophosphonamide [Au(bpta)(dedtc)] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.

DFT Insights into FEBID Stability: Condensed Study of Gold(I) Complexes with Phosphine Ligands

AbstractThis work examines the durability and responsiveness of XAuL precursors in the context of synthesizing Au‐nanomaterials. The study used density functional theory (DFT) simulations to look at the shapes, bond dissociation energies, and thermodynamic properties of a number of XAuL precursors. Within this framework, X denotes halogens Cl, Br, or I, whereas L denotes ligands such as PH3, PF3, PMe3, P(OMe)3, and P(NH2)3. Our investigations indicate that there is no discernible relationship between the lengths of XAuL bonds and binding energies. Small changes in bond dissociation free energy (▵BDG) serve as indicators of neutral precursors with low stability. The aforementioned precursors are essential for chemical vapor deposition. There are clear patterns that depend on the size of the halogen and the type of ligand when the ▵BDG values and interatomic distances in the XAuL precursors are looked at. Adding an electron to the precursor changes the length of the XAuL bond, which makes the ΔBDG values of anionic precursors lower than those of neutral precursors. The study is mostly about looking at how ligands L and XAu fragments interact with each other by looking at frontier molecular orbitals (FMOs). It has been shown that higher energy gap (ΔBDG) values lead to better interaction between the HOMO and LUMO orbitals of ligand L and XAu fragments. Furthermore, the research of electrophilicity emphasizes the significance of π‐back donation and the covalent energy involved in the bonding between XAu‐PR3. Thermodynamic study indicates that the dissociation processes exhibit more spontaneity under elevated temperatures and reduced pressures. The size of halogens affects spontaneity, with larger halogens exhibiting higher negative ▵BDG values. The study shows that IAuPMe3, BrAuPMe3, and ClAuPMe3 are stable starting materials for making gold nanoparticles using focused electron beam‐induced deposition (FEBID) in normal situations. This extensive study enhances our understanding of precursor design for Au‐nanofabrication by providing valuable insights into the stability, reactivity, and thermodynamic characteristics of XAuL precursors.

Spectroscopic Assessment of Doxorubicin (DOX)-Gemcitabine (GEM) Gold Complex Nanovector as Diagnostic Tool of Galectin-1 Biomarker.

The aim of this study is focused on the development of theranostic hybrid nanovectors based on gold-doxorubicin (DOX)-gemcitabine (GEM) complexes and their active targeting with Galectin-1 (Gal-1) as a promising therapeutic and prognostic marker in cancer. For this purpose, a gold salt (HAuCl4) interacts with antitumor drugs (DOX; GEM) by chelation and then stabilizes with dicarboxylic acid-terminated polyethylene glycol (PEG) as a biocompatible surfactant. The proposed methodology is fast and reproducible, and leads to the formation of a hybrid nanovector named GEM@DOX IN PEG-AuNPs, in which the chemo-biological stability was improved. All synthetic chemical products were evaluated using various spectroscopic techniques (Raman and UV-Vis spectroscopy) and transmission electron microscopy (TEM). To conceive a therapeutic application, our hybrid nanovector (GEM@DOX IN PEG-AuNPs) was conjugated with the Galectin-1 protein (Gal-1) at different concentrations to predict and specifically recognize cancer cells. Gal-1 interacts with GEM@DOX in PEG-AuNPs, as shown by SPR and Raman measurements. We observed both dynamic variation in the plasmon position (SPR) and Raman band with Gal-1 concentration. We identified that GEM grafted electrostatically onto DOX IN PEG-AuNPs assumes a better chemical conformation, in which the amino group (NH3+) reacts with the carboxylic (COO-) group of PEG diacide, whereas the ciclopenthanol group at position C-5' reacts with NH3+ of DOX. This study opens further way in order to built "smart nanomedical devices" that could have a dual application as therapeutic and diagnostic in the field of nanomedicine and preclinical studies associated.

Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Gold(I) Complex with a Photoactive Ligand Behaves as a Two-in-One Dual Metallaphotoredox Cross-Coupling Catalyst

Gold(I) Complex with a Photoactive Ligand Behaves as a Two-in-One Dual Metallaphotoredox Cross-Coupling Catalyst

Exploring the bonding and aromaticity of [Au3{C2H2N2E(L)2}3]+ (E = Si, Ge and L = –CH3, -H, -CF3, –NO2): Trinuclear gold superalkali complexes

Coinage metal [Cu, Ag, Au] complexes, with carbene analogous ligands, especially silylene, and germylene, have been getting attention in recent years for their potential applications, either in homogeneous catalysis or in photophysical properties. In this study, we have designed trinuclear gold complexes with different substituted silylene and germylene and observed that these trinuclear gold complexes are stable in cationic form and behave like a superalkali. Conceptual density functional theory (CDFT) based descriptors like electrophilicity give the idea about the reactivity of these superalkali complexes. Negative NICS values determine the aromatic nature of the trinuclear core of these complexes. Atom in molecules (AIM) study has been performed to gain a clear idea about the bonding nature of complexes. Energy decomposition analysis (EDA) suggests that electrostatic interaction stabilizes the complex. First-order hyperpolarizability calculation confirms their high nonlinear optical (NLO) properties.

Hyper-enrichment of gold via quartz fracturing and growth of polymetallic melt droplets

Abstract Gold precipitation in hydrothermal systems is traditionally attributed to supersaturation of gold due to decreasing gold complex stability triggered by changes in physicochemical conditions of the ore fluid. However, ultrahigh-grade gold veins in orogenic (shear zone related) gold deposits can contain kilograms per tonne of gold or more, in marked contrast to the typically very low gold concentrations (tens of parts per billion) in fluid. The gold mineral assemblage is commonly restricted to native gold and/or Au-(Ag)-tellurides and occurs in micro-fractures of sheared quartz veins. Textural and compositional characterization of such assemblages, coupled with hydrothermal diamond anvil cell experiments and heating-freezing experiments, provides evidence for an alternative ultrahigh-grade gold enrichment mechanism via growth of polymetallic melt droplets induced by quartz fracturing. We propose that polymetallic melt droplets of Au-Ag-Te-Bi–rich composition form through adsorption-reduction of metal complexes on fractured quartz surfaces, where surface silanol groups and hydrogen serve as reductants. The melt droplets subsequently grow by catalyzing reduction of metal complexes and absorbing metals from fluids percolating in the fractured quartz network. The mobile and reactive polymetallic melt droplets can repeatedly react with the fluid on protracted quartz fracturing and efficiently continue to scavenge gold from multiple pulses of gold-undersaturated ore fluids.

Investigation of gold-amino acid interactions using Fourier Transform Infrared spectroscopy and correlation with gold dissolution; Studies at different pH values

Recent developments in the field of gold leaching using amino acids have generated an interest in understanding the bonding/interactions involved in gold amino acid complexation. So far, only Density Function Theory (DFT) models have predicted the bonding of gold with amino acids, and there has been limited experimental work to verify the postulated quantum models. This study therefore aims to address the identification of amino-gold interactions using Fourier Transform Infrared spectroscopy (FTIR) and interrogate the predicted DFT interactions of gold and amino acids. The selected amino acids for this investigation were glycine, alanine, cysteine and histidine. Interactions were investigated at different pH levels corresponding to the isoelectric point and deprotonation points of respective amino acids. In addition to the FTIR investigation, gold dissolution experiments were conducted to establish a possible relationship between the interactions and gold dissolution at the explored pH points. FTIR analysis indicated that gold forms complexes with amino acids through N–Au, O–Au, and S–Au bonds. These bonds were evidenced by observed peak changes in the NH3+, COO−, and S-associated IR vibration peaks during the complexation process. In turn, the IR vibration peaks supported the DFT predictions of the active site for the bonding between gold and amino acids. Notably, the analysis revealed significant vibrational shifts in the characterization peaks of ligands at the deprotonation pH across all four amino acids, signifying a high interaction between gold and amino acids with high pH levels. Moreover, the dissolution of pure gold using the four amino acids at 0.5 M concentration of amino acid, 187 mg/L solid w/v, 1 % H2O2 and 300 rpm agitation indicated that gold dissolution was more favourable at the deprotonation pH compared to the isoelectric ph. Overall, the results showed that high dissolution was observed at deprotonation pH that corresponded to high FTIR peak shifts observed on deprotonated amino acid complexation. Lastly, the study hints at a possible correlation between the nature of gold amino-acid complexation and the extent of gold dissolution, which could require further investigation.

Silver and Gold Complexes with NHC-Ligands Derived from Caffeine: Catalytic and Pharmacological Activity.

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A3-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated.

Gold(I) N‐heterocyclic carbene (NHC) complexes containing 6‐mercaptopurine derivatives and their in vitro anticancer and anti‐inflammatory effects

A series of eight N‐heterocyclic carbenes (NHC) gold(I) complexes, involving 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (iPr) ligand in combination with 6‐mercaptopurine derivatives (HL1–8), has been prepared and thoroughly characterized, including elemental analysis, mass spectrometry, infrared and multinuclear NMR spectroscopy, and single crystal X‐ray analysis. The complexes, showing general composition of [Au (iPr)(Ln)] 1–8, were evaluated for their in vitro cytotoxicity against four human cancer cell lines including A2780 (ovarian) and A2780R (ovarian Cisplatin resistant), PC3 (prostate) and MCF‐7 (breast), and normal human MRC‐5 cells (lung fibroblasts). The complexes revealed significant cytotoxicity, with the best IC50 values ≈ 3.4–6.4 μM against A2780 and reasonable selectivity. Cellular effects of the selected complexes on the A2780 cells were evaluated using various flow cytometry assays. Complexes 1, 3, and 4 showed a strong pro‐apoptotic effect and a strong effect on the loss of mitochondrial membrane potential. These findings indicate that their major mechanism of action is based on the collapse of the mitochondrial metabolism and activation of the intrinsic signaling pathway of apoptosis, consequently resulting in cell death. The complexes 1–8 revealed only negligible effect on the production of inflammatory‐related cytokine (TNF‐α), as well as the activation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) or peroxisome proliferator‐activated receptor gamma (PPARγ). Moreover, the shotgun proteomic analysis was performed, and the obtained results suggest that the mechanism of action of complexes 1, 3, and 4 differs somewhat from that of Auranofin.

Synthesis, characterization and anticancer activity of Ni(II), Cu(II), Pd(II) and Au(III) complexes derived from novel Mannich base

AbstractNew four complexes of Ni(II), Cu(II), Pd(II), and Au(III) were derived from the tridentate ligand 3‐((3‐(4‐hydroxyphenyl)‐5‐mercapto‐4H‐1,2,4‐triazol‐4‐yl)(3‐oxobutyl)amino)naphtho[2,3‐b]furan‐2(3H)‐one (L), which synthesized using condensation reaction of formaldehyde, acetone, and secondary amine (Mannich reaction). The secondary amine is a heterocyclic compound possesses two rings, naphthafuran and triazole, both rings prepared through intermolecular cyclization reactions. Considering that naphthafuran‐2‐one derived from α‐amino nitrile. The α‐amino nitrile compound contains the other triazole ring which illustrated to the structure through successive steps. The compounds were characterized using elemental analysis (C.H.N.S), FT‐IR, ultraviolet–visble spectroscopy, thermal gravimetric analysis (TGA), flame atomic absorption, molar conductivity, and magnetic susceptibility measurements. Accordingly, the probable geometries of the complexes were suggested as square planner, and they have electrolytic nature. Thus, chemical formula; [NiLCl]Cl·6H2O, [CuLCl]Cl·2H2O, [PdLCl]Cl·2H2O, and [AuLCl]Cl2·3H2O. Cytotoxic effect was studied on brain cancer cell line (AMJM cell line) at different concentrations for L and complexes. The results showed that gold(III) complex has the highest cytotoxicity among all compounds.

Polymer Backbone Chemistry Shapes the Alkaline Stability of Metallopolymer Anion-Exchange Membranes.

Anion-exchange membrane fuel cells and water electrolyzers have garnered significant attention in past years due to their potential role in sustainable and affordable energy conversion and storage. However, the chemical stability of the polymeric anion-exchange membranes (AEMs), the key component in these devices, currently limits their lifespan. Recently, metallopolymers have been proposed as chemically stable alternatives to organic cations, using metal centers as ion transporters. In metallopolymer AEMs, various properties such as alkaline stability, water uptake, flexibility, and performance, are determined by both the metal complex and polymer backbone. Herein we present a systematic study investigating the influence of the polymer backbone chemistry on some of these properties, focusing on the alkaline stability of low-oxophilicity gold metallopolymers. Despite the use of a common N-heterocyclic carbene ligand, upon gold metalation using the same reaction conditions, different polymer backbones end up forming different gold complexes. These findings suggest that polymer chemistry affects the metalation reaction in addition to the other properties relevant to AEM performance.

Investigation on Gold Dissolution Performance and Mechanism in Imidazolium Cyanate Ionic Liquids.

To explore green gold leaching reagents, a series of imidazolium cyanate ionic liquids (ILs), 1-ethyl-3-methyl-imidazolium cyanate ([C2MIM][OCN]), 1-propyl-3-methyl-imidazolium cyanate ([C3MIM][OCN]) and 1-butyl-3-methyl-imidazolcyanate ([C4MIM][OCN]) were synthesized and characterized by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR) and thermogravimetric (TG) analysis. In this research, the imidazolium cyanates were utilized as a solute, which not only decreased the usage of ILs but also increased their gold dissolution capability. The gold dissolution performances of three imidazolium cyanates were characterized by dynamic leaching test and Scanning Electron Microscopy (SEM). The results show that the all three imidazolium cyanates had a gold dissolution ability, and the shorter the carbon chain on the imidazole ring in imidazolium cyanate, the faster the gold dissolution rate. The gold dissolution performance of [C2MIM][OCN] was the best, and the weight loss of gold leaf was 2.9 mg/cm2 at 40 °C after 120 h dissolution in [C2MIM][OCN] mixed with 10 wt. % water. Besides this, the gold dissolution rate increased with the increase in the concentration of imidazolium cyanates as well as the reaction temperature. The gold dissolution performances of imidazolium cyanates in different solvents including water, acetonitrile, dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were also investigated, and the weaker the polarity of the solvent, the more conducive it was to the gold dissolution reaction. The mechanism of gold dissolution by imidazolium cyanates was investigated through NMR spectroscopy and Electrospray Ionization Mass Spectrometry (ESI-MS). It was inferred that during the process of gold dissolution, Au was oxidized to Au+ and the imidazolium cations were deprotonated to form N-heterocyclic carbenes, which coordinated with gold to form gold complexes and achieve gold dissolution.

A Photocatalytic Approach for the Synthesis of L‐Shape Bicyclic NHC Ligands

AbstractL‐shape N‐Heterocyclic Carbenes (NHCs) based on the imidazo[1,5‐a]pyridine (ImPy) scaffold have recently gained considerable interest as the true carbene ligand analogues of the popular dialkylbiarylphosphines, better known as Buchwald phosphines. Nevertheless, the substitution pattern of ImPy ligands is still rather limited due to synthetic access issues. We report herein an efficient and versatile visible light photocatalytic strategy to access L‐shape bifunctional ImPy ligands laterally‐functionalized by a phenol group. Mechanistic investigations supported by density functional theory (DFT) reveal that the excited state of the iridium photocatalyst undergoes either a reductive quenching (SET process) or an energy‐transfer quenching (EnT process) depending on the nature of the counterion of the 5‐bromoimidazo[1,5‐a]pyridinium substrate salt. Moreover, the bifunctional character of these new family of L‐shape ImPy ligands is demonstrated by the preparation of a gold(I) complex exhibiting a free OH function capable of intermolecular hydrogen bonding. This work highlights the advantage of visible light photocatalysis in the synthesis of advanced NHC ligand structures, a strategy that has not yet been considered despite its potential benefits in terms of versatility, diversity and practicability.

Cationic Bis(Gold) Indenyl Complexes.

Reaction of (P)AuOTf [P=P(t-Bu)2o-biphenyl] with indenyl- or 3-methylindenyl lithium led to isolation of gold η1-indenyl complexes (P)Au(η1-inden-1-yl) (1 a) and (P)Au(η1-3-methylinden-1-yl) (1 b), respectively, in >65 % yield. Whereas complex 1 b is static, complex 1 a undergoes facile, degenerate 1,3-migration of gold about the indenyl ligand (ΔG≠ 153K=9.1±1.1 kcal/mol). Treatment of complexes 1 a and 1 b with (P)AuNTf2 led to formation of the corresponding cationic bis(gold) indenyl complexes trans-[(P)Au]2(η1,η1-inden-1,3-yl) (2 a) and trans-[(P)Au]2(η1,η2-3-methylinden-1-yl) (2 b), respectively, which were characterized spectroscopically and modeled computationally. Despite the absence of aurophilic stabilization in complexes 2 a and 2 b, the binding affinity of mono(gold) complex 1 a toward exogenous (P)Au+ exceed that of free indene by ~350-fold and similarly the binding affinity of 1 b toward exogenous (P)Au+ exceed that of 3-methylindene by ~50-fold. The energy barrier for protodeauration of bis(gold) indenyl complex 2 a with HOAc was ≥8 kcal/mol higher than for protodeauration of mono(gold) complex 1 a.

DFT-Enabled Development of Hemilabile (P∧N) Ligands for Gold(I/III) RedOx Catalysis: Application to the Thiotosylation of Aryl Iodides.

Ligand-enabled oxidative addition of Csp2-X bonds to Au(I) centers has recently appeared as a valuable strategy for the development of catalytic RedOx processes. Several cross-coupling reactions that were previously considered difficult to achieve were reported lately, thus expanding the synthetic potential of gold(I) complexes beyond the traditional nucleophilic functionalization of π-systems. MeDalPhos has played an important role in this development and, despite several studies on alternative structures, remains, so far, the only general ligand for such process. We report herein the discovery and DFT-enabled structural optimization of a new family of hemilabile (P∧N) ligands that can promote the oxidative addition of aryl iodides to gold(I). These flexible ligands, which possess a common 2-methylamino heteroaromatic N-donor motif, are structurally and electronically tunable, beyond being easily accessible and affordable. The corresponding Au(I) complexes were shown to outperform the reactivity of (MeDalPhos)Au(I) in a series of alkoxy- and amidoarylations of alkenes. Their synthetic potential and comparatively higher reactivity were further highlighted in the thiotosylation of aryl iodides, a challenging unreported C-S cross-coupling reaction that could not be achieved under classical Pd(0/II) catalysis and that allows for general and divergent access to aryl sulfur derivatives.

Manipulation of aurophilicity in constructed clusters of gold(I) complexes with boosted luminescence and smart responsiveness

High-performance luminescent gold(I) complexes have attracted considerable attention due to their potential applications in various fields, but their construction is a significantly challenging task. Herein, we designed and synthesized a series of novel dinuclear gold(I) complexes 1–4 based on 1,2-bis(diphenylphosphino)benzene and 1,4-bis(diphenylphosphino)benzene frameworks, where para-substitutions of benzene ring were employed for comparison and bulky t-butyl groups were introduced into carbazole ligands to assist flexibly regulating the aurophilicity. Among them, the structure of complex 1 was confirmed by single-crystal X-ray diffraction, and all the complexes exhibited typical aggregation-induced emission characteristics. Due to the construction of intramolecular aurophilicity and the formation of molecular clusters, noticeable enhancement of the luminescent efficiency was achieved for the core complex 1. Together with the introduction of flexible t-butyl groups, good responsiveness towards external mechanical force and solvent vapors were also realized. Moreover, the specific bioimaging ability of complex 1 towards cancer cells was demonstrated. Thus, this work presents the crucial capability of aurophilic manipulation in tuning the luminescence and smart behaviors of gold complexes, and it will open a new route to developing high-performance luminescent materials.