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The present work opens with an acknowledgement to the research activity performed by Luciana Naldini while affiliated at the Università degli Studi di Sassari (Italy), in particular towards gold complexes and clusters, as a tribute to her outstanding figure in a time and a society where being a woman in science was rather difficult, hoping her achievements could be of inspiration to young female chemists in pursuing their careers against the many hurdles they may encounter. Naldini's findings will be a key to introduce the most recent results in this field, showing how the chemistry of gold compounds has changed throughout the years, to reach levels of complexity and elegance that were once unimagined. The study of gold complexes and clusters with various phosphine ligands was Naldini's main field of research because of the potential application of these species in diverse research areas including electronics, catalysis, and medicine. As the conclusion of a vital period of study, here we report Naldini's last results on a hexanuclear cationic gold cluster, [(PPh3)6Au6(OH)2]2+, having a chair conformation, and on the assumption, supported by experimental data, that it comprises two hydroxyl groups. This contribution, within the fascinating field of inorganic chemistry, provides the intuition of how a simple electron counting may lead to predictable species of yet unknown molecular architectures and formulation, nowadays suggesting interesting opportunities to tune the electronic structures of similar and higher nuclearity species thanks to new spectroscopic and analytical approaches and software facilities. After several decades since Naldini's exceptional work, the chemistry of the gold cluster has reached a considerable degree of complexity, dealing with new, single-atom precise, materials possessing interesting physico-chemical properties, such as luminescence, chirality, or paramagnetic behavior. Here we will describe some of the most significant contributions. [ABSTRACT FROM AUTHOR]

Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity. [Display omitted] • Design of efficient aza-BODIPY-based homo-bimetallic gold(I) theranostics. • High in vitro anti-proliferative properties (4 < IC 50 < 10 μM on 4 cancer cell lines). • Significant anti-cancer effect of aza-BODI-Au-1 in tumor-bearing BALB/c mice. • The compounds can be tracked in vitro and in vivo by NIR-optical imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • isothiourea gold complexes were evaluated as novel DPP-IV inhibitors. • In vitro enzyme inhibition assay was performed. • Moderate DPP-IV inhibitory activity observed in in cellulo model. • Mechanistic studies were performed to identify mechanism of inhibition. About 100 million people worldwide have type II diabetes (T2D), making it one of the most common metabolic diseases. DPP-IV (dipeptidyl peptidase-IV) inhibitors are new class of anti-diabetic drugs. Gold complexes are known for diverse biological activities. Considering these precedents, and growing interest in developing metal-based enzyme inhibitors, we report here the DPP-IV inhibitory potential of cationic, and neutral chiral gold (I), and gold (III) isothiourea complexes. Colorimetric assay with recombinant DPP-IV enzyme was employed for initial screening. Kinetic based mechanistic studies were also performed on most active complexes. Efficiency of identified inhibitors in biological environment was assessed in in cellulo assay, using Caco-2 cell line. These complexes showed a good to moderate inhibition of DPP-IV with IC 50 values in the range of 22.0-99.0 µM, as compared to standard inhibitor, sitagliptin (IC 50 = 0.033 ± 0.04 µM). It was observed that steric, and electronic properties of the isothiourea ligands have profound effect on the DPP-IV inhibitory activity of these complexes. To the best of our knowledge this study reports for the first time isothiourea-based gold complexes as inhibitors of DPP-IV enzyme. These results thus provide an approach for exploring new insights into the development of effective agents against diabetes using incretin-based therapy. [ABSTRACT FROM AUTHOR]

• A panel of seven gold (I)/(III) compounds has been selected for proteomic studies. • The identified proteins by proteomics have been classified via Gene Ontology. • Three main modes of action highlighted: redox state, metabolism, protein synthesis. Gold compounds form an attractive class of cytotoxic metal compounds of potential application as anticancer agents. Notably, the mode of action of cytotoxic gold compounds appears to differ from that of the widely used anticancer Pt drugs -to which they were initially inspired- and to be basically DNA-independent. However, mechanistic details are still largely lacking for this class of metal-based drugs. To shed light on these issues we have developed a proteomic strategy that is capable of highlighting the perturbations in protein expression elicited by gold drugs in a selected cancer cell line with the final aim to disclose the underlying molecular mechanisms. In recent years, this type of strategy has been systematically applied, in our laboratory, to a representative panel of gold compounds including seven outstanding cytotoxic agents, i.e. six experimental gold(III) and gold(I) compounds and the clinical gold(I) drug, auranofin. A2780 human ovarian cancer cells were used as the standard cellular model for these studies. Proteins differentially expressed upon treatment were separated by 2-DE and identified by MALDI TOF and their meaning tentatively assessed through bioinformatic analysis. The occurrence of various and often overlapping molecular mechanisms was revealed. The affected proteins were found to belong -in most cases- to redox control systems and/or to the proteasome machinery implying that the severe cellular damage induced by gold compounds predominantly originates at these two distinct levels. However, for one Au(III) and one Au(I) compound, i.e. [(bipydmb-H)Au(OH)][PF 6 ] (bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine) (Aubipyc) and the bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(I) [Au(NHC) 2 ]PF 6 , a substantially greater number of proteomic alterations were detected pointing out, in both cases, to glucose metabolism as an additional target process of the cytotoxic action. The results that were obtained with the seven gold complexes are discussed in the frame of the available knowledge on anticancer gold drugs and their mechanisms. In general, our studies underscore the large amount of information that proteomic measurements may provide on the mode of action of metal-based drugs at the cellular level and delineate a very effective methodology for the identification of the respective cytotoxic mechanisms. We propose that the interpretation of the proteomic data in terms of the main affected cellular processes is further supported and validated through the implementation of complementary metabolomics and metallomics experiments. [ABSTRACT FROM AUTHOR]

Anticancer, cytotoxicity, gold complexes, mesoionic carbenes, metallodrugs Keywords: anticancer; cytotoxicity; gold complexes; mesoionic carbenes; metallodrugs EN anticancer cytotoxicity gold complexes mesoionic carbenes metallodrugs 8229 8229 1 06/07/21 20210604 NES 210604 B A challenging synthesis yields a bis(carbene) Au SP I sp -CNC pincer precursor complex b that may be oxidized to a remarkably redox-stable [Au SP III sp (CNC)Cl] SP + sp cation which shows significant cytotoxicity towards a breast cancer cell line. Cover Feature: A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation (Chem. Eur. J. 32/2021). [Extracted from the article]

The complexing of gold during dissolution of gold powder in donor-acceptor organic and aqueous-organic Au-DMSO-RX systems (where R=H or Bu, and X=Cl or Br) was studied. Ten complexes were produced, and their compositions and IR spectra in the 4000−200 cm range were determined. The data obtained were interpreted in terms of the concept of donor-acceptor electron transfer systems. [ABSTRACT FROM AUTHOR]

Luminescence from a gold(I) complex with an N-heterocycliccarbene-based ligand, 1 + ⋅NTf 2 - , increased rapidly upon the application of one-shot needlestick-stimulus. The weakly orange-emitting solid-state of 1 + ⋅NTf 2 - was prepared by cooling its melted liquid to 90 °C. Upon applying a weak pinpoint stimulus with a needle, this weakly orange-emitting solid state transformed into an intensively violet-blue-emitting state on a timescale of seconds. The emission after applying the stimulus could be visualized upon UV excitation even under ambient room light. This sequential phase transition from a stable solid to a liquid and then to a metastable solid could occur repeatedly without any measurable degradation of the complex. Various shapes could be prepared by casting the liquid-state complex into molds of different designs. This rapid response is thought to be triggered by the flexible intermolecular interactions in the kinetically generated aggregates formed upon cooling the liquid state, and by the strong Au-Au interactions in the thermodynamically stable crystals after applying the needlestick-stimulus., (© 2021 Wiley-VCH GmbH.)

• N-heterocyclic carbenes are multifunctional ligands to stabilize gold nanoparticles. • Top-Down and Bottom-Up synthesis of NHC@AuNPs has been achieved. • Size, shape and stability of NHC@AuNPs strongly depend on the NHC ligands. • Water soluble gold nanoparticles are useful tools in biomedicine. The unique properties and high synthetic flexibility of N-heterocyclic carbenes (NHCs) have made them highly attractive tools for the development of new nanomaterials and the fundamental study of their properties. In this review, we focus on the case of NHC-stabilized gold nanoparticles (NHC@AuNPs) with potential for biological applications. AuNPs are ubiquitous in biomedicine, where they serve as versatile scaffolds for drug/gene delivery, biosensing, imaging and therapy. In this context, our review aims at presenting an overview of the relatively few studies reporting on the synthesis and characterization of NHC@AuNPs, with emphasis on the strategies adopted to achieve water-soluble biocompatible nanoparticles. Overall, the possible combinatorial design of NHC ligand shell functionality opens to new perspectives for this relatively unexplored research area. [Display omitted] [ABSTRACT FROM AUTHOR]

A new class of chiral bicyclic [1,2,3]-triazolooxazine derived N -heterocyclic carbene (NHC) ligands and their palladium, silver, and gold complexes were synthesised in enantiopure form from commercially available, cheap amino acid without undertaking any chiral resolution. • New chiral bicyclic [1,2,3] triazolooxazine based NHC complexes of Ag(I), Au(I) and Pd(II). • Ag, Au and Pd represent only structurally characterized complexes of this type of ligands. • Preparation of these enantiopure ligands involved multi-step sequence from cheap chiral amino acids. A new class of chiral bicyclic [1,2,3]-triazolooxazine derived N -heterocyclic carbene (NHC) ligands was synthesised in its enantiopure form from commercially available, cheap amino acid without undertaking any chiral resolution. In particular, the bicyclic N -heterocyclic carbene precursor, (S)-7-benzyl-6,6-(R1) 2 –2-R2-[1,2,3]-triazolooxazinium iodide [R1 = R2 = Me (1a); R1 = H, R2 = Me (2a); R1 = H, R2 = Et (3a)] salts were conveniently prepared by the N -alkylation reactions of the corresponding [1,2,3]- triazolooxazine derivatives with alkyl iodides in ca. 37–73% yields. The copper mediated [3 + 2] cycloaddition reaction of the PhCH 2 CH(N 3)CR 2 OH (R = H, Me) azido alcohol compounds and propargyl bromide gave the desired [1,2,3]-triazolooxazines. These chiral bicyclic [1,2,3]- triazolooxazine derived N -heterocyclic carbene ligands were characterised in the form of its silver (NHC)AgCl (1–3) b , gold (NHC)AuCl (1–3) c , and the palladium (NHC) 2 PdCl 2 (1–3) d and the PEPPSI type (NHC)PdI 2 (NC 5 H 5) (1–3) e complexes (NHC = (S)-7-benzyl-6,6-(R1) 2 –2-R2-[1,2,3]-triazolooxazin-3-ylidene; R1 = H, Me and R2 = Me, Et; PEPPSI = Pyridine Enhanced Precatalyst Preparation Stabilisation and Initiation). [ABSTRACT FROM AUTHOR]

Gold phosphine derivatives such as thiolates have been recently proposed as catalysts or catalyst precursors. The relevance of the supramolecular environment on the fine-tuning of the catalytical activity on these compounds incentivizes the use of tools that are convenient to characterize in detail the non-covalent landscape of the systems. Herein, we show the molecular and supramolecular diversity caused by the changes in the fluorination pattern in a family of new XPhos goldfluorothiolate derivatives. Furthermore, we studied the supramolecular interactions around the Au centers using quantum chemical topology tools, in particular the quantum theory of atoms in molecules (QTAIM) and the non-covalent interaction index. Our results give detailed insights into the fluorination effects on the strength of intramolecular and intermolecular interactions in these systems. We have also used QTAIM delocalization indexes to define a novel hapticity indicator. Finally, we assessed the trans influence of the fluorothiolates on the phosphine in terms of the change in the δ 31P-NMR. These results show the feasibility of the use of fluorination in the modulation of the electronic properties of Buchwald phosphine gold(I) compounds, and thereby its potential catalytic activity. [ABSTRACT FROM AUTHOR]

• Gold(I) complexes with N -phosphinoamide ligands were prepared. • Crystal structures were determined. • Interplay of intermolecular interactions of various types was observed in the solid state. [AuCl{RC(O)NHPPh 2 -κ P }] gold(I) complexes with varying amide substituents (R = Me, Ph and ferrocenyl) were prepared, characterized by elemental analysis and spectroscopic methods (mass spectrometry and multinuclear NMR and IR spectroscopy) and further studied by single-crystal X-ray crystallography with a particular focus on solid-state interactions. In all cases, the crystal assembly was based mainly on conventional hydrogen bonds between the amide moieties. However, while in chloroform-solvated [AuCl{MeC(O)NHPPh 2 -κ P }], these interactions were supported by π⋅⋅⋅π stacking of aromatic rings, in the crystal structures of the complexes bearing phenyl and ferrocenyl substituents, they cooperated with aurophilic interactions of the Au(I) centers, which in turn affected the C O⋯HN hydrogen bonds. [ABSTRACT FROM AUTHOR]

A cationic AuI N‐heterocyclic carbene complex featuring caffeine‐based ligands has shown potent and selective anticancer effects in ovarian cancer cells. This organogold compound is remarkably stable in physiological conditions. Therefore, the observed therapeutic effects are mainly due to non‐covalent interactions of the gold compound with its pharmacological targets. Among the latter, DNA secondary structures—G‐quadruplexes—play a pivotal role in the mechanisms of anticancer action. More information can be found in the Full Paper by S. M. Meier‐Menches, A. Casini, C. Gerner, et al. on page 15528. [ABSTRACT FROM AUTHOR]

Starting from commercially available DMSAuCl and diazonium salts, cationic [ N ∧ C ∧ N ]Au III complexes were synthesized in a selective, photosensitizer-free, photochemical reaction by irradiation with blue LED light. This new protocol represents the first easy synthesis of these types of pincer complexes in moderate to excellent yield starting from a readily available gold(I) precursor with nitrogen as the only by-product. Owing to the disadvantages of known protocols, especially the toxicity in the case of a transmetalation with mercury or the necessity for a mostly twofold excess of a gold precursor, this method offers an attractive alternative towards this kind of gold(III) complexes. In addition, the first arylated [ N ∧ C ∧ N ]Au(III) pincer complex was synthesized by using this technology., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several Au I and Au III complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds., (© 2021 Wiley-VCH GmbH.)

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) Au I -CNC pincer complex suitable for oxidation to the redox-stable [Au III (CNC)Cl] + cation. Although the ligand salt and the [Au III (CNC)Cl] + complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the Au III complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [Au III (CNC)Cl] + complex behaves as a partial DNA intercalator. In silico screening indicated that the [Au III (CNC)Cl] + complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the Au III ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

• One Step synthesis of complex drug nanovector. • Easy conjugation of Anti –EFGR onto DTX IN PEG-AuNPs. • Feasibility test on three-dimensional (3D) tumoroids. • Good Stability of drug-complex. • Good Efficacity. Docetaxel (DTX) is an anticancer treatment widely used in the clinic for the treatment of various human malignancies, including Non-Small-Cell Lung Cancer (NSCLC). Its low water solubility and systemic toxicity, however, negatively impact the clinical application of such drug. In order to improve DTX solubility in biological fluids and decrease its adverse effects in patients, the scientific community is currently focusing on developing drug delivery systems where DTX is the payload. In this context, the present study aims at presenting a step forward in the development of platforms based on gold complexes for multifunctional approaches (theragnostic tools) and stimuli-responsive therapies. Tetrachloroauric acid (HAuCl 4) were complexed with the antitumor drug and dicarboxylic acid-terminated polyethylene-glycol (PEG) to form the nanometric complex named DTX-Au-PEG. Following reduction with sodium borohydride (NaBH 4), the DTX-Au-PEG complex formed hybrid-metal nanoparticles (DTX IN PEG-AuNPs), where DTX was protected in the gold core embedded within the polymer chains. To achieve therapeutic targeting, DTX-Au-PEG complex and DTX IN PEG-AuNPs were chemical combined with the human anti-EGFR polyclonal antibody, which recognizes the hERG1 channel aberrantly expressed on the membrane of human lung cancer cells. The active targeting was demonstrated by various analytical techniques (Raman and UV–vis spectroscopies); whereas, in vitro experiments on tissue-mimetic, three-dimensional (3D) tumoroids grown at the Air-Liquid Interface (ALI) demonstrated that DTX encapsulation within a gold core strongly influenced the drug efficacy, with a significant increase of the DTX therapeutic index when AuNPs were specifically targeted against EGFR. Collectively, our study demonstrated that a drug delivery system based on Au (III)-DTX complexes constitutes an encouraging chemical approach to build Au (III) complexes into real chemotherapeutic drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)–Au(I) dinuclear complexes were synthesized; they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)–Au(I) complex not functionalized with carbohydrates. [ABSTRACT FROM AUTHOR]

The discovery of cisplatin made a difference in the way that chemotherapy was understood. Since then, and in order to improve the effectiveness and the clinical problems related to this kind of metallodrugs, several metals have been investigated as an alternative to this therapy. Due to the chemical similarities with Pt(II), Au(III) is a promising metal for this purpose. Nevertheless, the stabilization of this oxidation state in physiological conditions is still a difficult goal to achieve. In this research, we have studied the cyclometallation as a strategy to make stable Au(III) complexes, and we have evaluated these compounds as candidates to be used in the treatment of colon cancer. To achieve our goals, we made a huge effort to design a general strategy to obtain cycloaurated complexes, without organomercurial compounds. Thus, we have synthesized the cyclometallated Au(III) derivatives from the corresponding [AuCl 3 (N –CH)] complex and we have tested some ADME-tox properties of these compounds. The partition coefficient showed that, although [AuCl 3 (N –CH)] were more water-soluble, cyclometallated species present a better balance between hydro- and lipophilicity. That is why cycloaurated complexes were modified by the coordination of O-donor ligands and studied as anticancer drugs for colon cancer (Caco-2/TC7 cell line). The precursors ([AuCl 3 (N –CH)]) and starting cyclometallated complexes did not present any effect on tumour or normal cell proliferation. However, complex [Au(Phe)(ppy)]Cl presents a better antiproliferative effect than cisplatin on tumour cells and a selectivity 9-times greater towards tumour cells than towards normal cells. Some interesting conclusions actually arise from these results for a better future structural design, and thus to achieve more active anticancer drugs. Image 1 • Synthesized [AuCl 3 (N –CH)] and [Au(C^N)Cl 2 are stable under physiological conditions. • Cycloaurated complexes [Au(C^N)Cl 2 seem to be better biodistributable. • [Au(C^N)X 2 do not present effect in tumour or normal Caco-2/TC7 cell. • Only [Au(ppy)(Phe)], Only [Au(ppy)(Phe)]Cl showed cytotoxic properties (1.32 ± 0.12 μM) on tumour Caco-2 cell. [ABSTRACT FROM AUTHOR]

Alkyne is a useful functionality incorporated in proteins for site-selective bioconjugation reactions. Although effective bioconjugation reactions such as copper(I)-catalyzed and/or copper-free 1,3-dipolar cycloadditions of alkynes and azides are the most common approaches, the development of new alkyne-based bioconjugation reactions is still an ongoing interest in chemical biology. In this work, a new approach has been developed for selective modification of alkyne-linked peptides and proteins through the formation of arylacetylenes by a cross-coupling reaction of 6-membered ring cyclometalated gold(III) (C^N) complexes (HC^N = 2-arylpyridines) with terminal alkynes. Screening of the reaction conditions with a series of cyclometalated gold(III) complexes with phenylacetylene gave an excellent yield (up to 82%) by conducting the reaction in slightly alkaline aqueous conditions. The reaction scope was expanded to various alkynes, including alkyne-linked peptides to achieve up to >99% conversion. Using fluorescent dansyl (1l) and BODIPY (1m)-linked gold(III) complexes, alkyne-linked lysozyme has been selectively modified. [ABSTRACT FROM AUTHOR]

Recent rapid development in homogeneous gold catalysis affords an alternative and particularly thriving strategy for the generation of gold carbenes through gold-catalyzed oxidation/amination/cycloaddition of alkynes, while it avoids the employment of hazardous and potentially explosive diazo compounds as starting materials for carbene generation. In addition to facile and secure operation, gold carbenes generated in this strategy display good chemoselectivity distinct from other metal carbenes produced from the related diazo approach. N-heterocyclic carbene (NHC) gold is a special metal complex that can be used as ancillary ligands, which provides enhanced stability and can also act as an efficient chiral directing group. In this review, we will present an overview of these recent advances in alkyne oxidation/amination/cycloaddition by highlighting their specificity and applicability, aiming to facilitate progress in this very exciting area of research. [ABSTRACT FROM AUTHOR]

Keywords: gold complexes; native ESI-MS; RNA binding; tristetraprolin; zinc finger This powerful MS technique can also be utilized to probe reactivity of RNA bound zinc fingers, and it is reported that RNA has a protective effect towards Gold Finger reactivity with tristetraprolin. Gold complexes, native ESI-MS, RNA binding, tristetraprolin, zinc finger. [Extracted from the article]

[Display omitted] • Synthesis and characterization of new NHC silver and gold complexes. • Catalysts for A3-coupling (aldehyde-alkyne-amine) reaction. • Very high conversion (also 100%) in A3 reactions. • DFT calculation rationalized the catalytic activity on NHC ligands. Silver and gold complexes bearing unsaturated N -heterocyclic carbene ligands, with unsymmetrical N -substituents and hydrogen or chlorine on backbone, have been synthetized and their efficiency tested in A3-coupling (aldehyde–alkyne–amine) reactions. Gold complexes showed higher activity than corresponding silver ones, even if the significant role of the backbone substituents should not be neglected. Indeed, complexes with chlorine substituted backbone were more efficient than hydrogen analogous. According to DFT calculations, electronic differences among complexes are able rationalize the different catalytic behavior, whereas steric properties play a minor part. [ABSTRACT FROM AUTHOR]

The design of multi-targeted drugs has gained considerable interest in the last decade thanks to their advantages in the treatment of different diseases, including cancer. The simultaneous inhibition of selected targets from cancerous cells to induce their death represents an attractive objective for the medicinal chemist in order to enhance the efficiency of chemotherapy. In the present work, several alkynyl gold(I) phosphane complexes derived from 3-hydroxyflavones active against three human cancer cell lines, colorectal adenocarcinoma Caco-2/TC7, breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2, have been synthesized and characterized. Moreover, these compounds display high selective index values towards differentiated Caco-2 cells, which are considered as a model of non-cancerous cells. The antiproliferative effect of the most active complexes [Au(L2b)PPh 3 (3b) and [Au(L2c)PTA] (4c) on Caco-2 cells, seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2 and alteration of the activities of the redox enzymes thioredoxin reductase and glutathione reductase. Both complexes triggered cell death by apoptosis, alterations in cell cycle progression and increased of ROS production. These results provide support for the suggestion that multi-targeting approach involving the interaction with cyclooxygenase-1/2 and the redox enzymes that increases ROS production, enhances cell death in vitro. All these results indicate that complexes [Au(L2b)PPh 3 and [Au(L2c)PTA] are promising antiproliferative agents for further anticancer drug development. Targeted therapies for cancer treatment have revolutionized the concept of oncological medicine. However, the single-target therapy is vanishing in favour of a multi-target approach, where new drugs are able to simultaneously target different molecules. Here we describe new alkynyl gold(I) phosphane complexes derived from 3-hydroxyflavones, whose mechanism of action involves cell death via two independent targets. Image 1 • Multi-targeted mechanism of action promoted by Alkynyl Gold(I) derivatives. • Interaction with COX-1/2 enzyme. • Interaction with the redox enzymes TrxR and GR leading to an increased ROS production. • Cell death via the intrinsic pathway and alteration of cell cycle progression. [ABSTRACT FROM AUTHOR]

Direct targeting of intrinsically disordered proteins, including MYC, by small molecules for biomedical applications would resolve a longstanding issue in chemical biology and medicine. Thus, we developed gold-based small-molecule MYC reagents that engage MYC inside cells and modulate MYC transcriptional activity. Lead compounds comprise an affinity ligand and a gold(I) or gold(III) warhead capable of protein chemical modification. Cell-based MYC target engagement studies via CETSA and co-immunoprecipitation reveal specific interaction of compounds with MYC in cells. The lead gold(I) reagent, 1, demonstrates superior cell-killing potential (up to 35-fold) in a MYC-dependent manner when compared to 10058-F4 in cells including the TNBC, MDA-MB-231. Subsequently, 1 suppresses MYC transcription factor activity via functional colorimetric assays, and gene-profiling using whole-cell transcriptomics reveals significant modulation of MYC target genes by 1. These findings point to metal-mediated ligand affinity chemistry (MLAC) based on gold as a promising strategy to develop chemical probes and anticancer therapeutics targeting MYC., (© 2020 Wiley-VCH GmbH.)

In this work, we show that intramolecular hydrogen bonding can be used to stabilize tri-coordinated phosphane-gold(I) complexes. Two molecular structures of 2-(diphenylphosphino)benzoic acid (L) coordinated to a gold(I) atom were determined by single-crystal X-ray diffraction. The linear L-Au-Br shows a standard linear coordination and dimerizes via hydrogen bonds of the carboxylic acid. Upon addition of two additional phosphane ligands the complex [L 3 Au]X is formed which is stabilized by three intramolecular -C(O)O-H … X hydrogen bonds as proven by the X-ray structure of the respective chlorido-complex. X-ray powder diffractograms suggest the same structure also for X -  = Br - and I - ., Supplementary Information: The online version contains supplementary material available at 10.1007/s00706-021-02843-2., (© The Author(s) 2021.)

We herein report on new synthetic strategies for the preparation of pyridine and imidazole substituted 2,2'-dihalo biphenyls. These structures are pre-ligands suitable for the preparation of respective stannoles. The latter can successfully be transmetalated to K[AuCl 4 ] forming non-palindromic [(C^C^D)Au III ] pincer complexes featuring a lateral pyridine (D=N) or N-heterocyclic carbene (NHC, D=C') donor. The latter is the first report on a pincer complex with two formally anionic sp 2 and one carbenic carbon donor. The [(C^C^D)Au III ] complexes show intense phosphorescence in solution at room temperature. We discuss the developed multistep strategy and touch upon synthetic challenges. The prepared complexes have been fully characterized including X-ray diffraction analysis. The gold(III) complexes' photophysical properties have been investigated by absorption and emission spectroscopy as well as quantum chemical calculations on the quasi-relativistic two-component TD-DFT and GW/Bethe-Salpeter level including spin-orbit coupling. Thus, we shed light on the electronic influence of the non-palindromic pincer ligand and reveal non-radiative relaxation pathways of the different ligands employed., (© 2020 The Authors. Published by Wiley-VCH GmbH.)