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Many ligands are structurally rigid and well-defined, e.g. N-heterocyclic carbenes display a fan-like structure with a defined buried volume. Here, we break this dogma by introducing more flexibility around the catalytically active center by using acyclic (diamino)carbene (ADC) ligands. The ADC ligand was constructed in a straightforward protocol on the ruthenium center via methyl isocyanide coordination and subsequent reaction with amines such as pyrrolidine. Ligand flexibility in the formed (pyrrolidine)(methylamine)carbene ruthenium complex Ru-2 was demonstrated both in solution (variable temperature NMR) and in the solid state through crystallographic identification with the protic NH site oriented either distal or proximal to the ruthenium center. In contrast to their cyclic analogues, the Ru-ADC complexes are highly active in base-free transfer hydrogenation, with turnover numbers >1000. The base-free conditions allowed for the transformation of substrates with base-sensitive groups such as esters, amides, acids, and amines, substrates that typically fail to undergo transfer hydrogenation under classical conditions. The absence of base also enabled late-stage hydrogenation of more complex substrates, and it avoids complications such as corrosion attributed to KOH and related strong bases. Show less

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. Show less

The direct and atom economic synthesis of azulenyl-substituted gold(I) carbene complexes, based on the modular template synthesis using gold(I) isonitrile complexes and amine nucleophiles, is presented. First, two azulenyl-substituted isonitriles as ligands were synthesized from a functionalizable azulene derivative, the latter stemming from a gold-catalyzed dimerization of internal alkynes. These azulene-bound gold(I) isonitrile complexes allow the smooth nucleophilic attack by both aliphatic and aromatic amines. The newly synthesized azulene-substituted gold(I) carbene complexes were evaluated for in vitro anticancer activity against multiple human cancer cell lines. Six lead compounds demonstrated potent and selective cytotoxicity, exceeding that of cisplatin by at least an order of magnitude in resistant and aggressive cancer models. Structure–activity relationship analysis revealed that specific ligand modifications, such as the position of the azulene moiety tethered to the carbene unit or nitrogen-bound ethyl or cyclic groups, are critical for enhancing the anticancer activity. Show less

The design and synthesis of a multifunctional covalent organic framework (COF) for various applications have been considered a big challenge. Herein, we report the construction of a novel porphyrin-based Au-acyclic diaminocarbene (Au-ADC)-linked COF (abbreviated as Au-ADC-Por-COF) via a metal-mediated nucleophilic addition reaction. The resultant multifunctional Au-ADC-Por-COF revealed an outstanding performance in a cascade catalyzing photocatalytic sulfide oxidation under visible-light irradiation and intermolecular nucleophilic addition. This research might open a new way for the design of advanced materials with unprecedented structures and catalytic activities. Show less

Helicates and helicenes represent two prominent classes of synthetic molecular helices, desirable for their potential in chiroptical applications. Incorporating boron into their backbone presents a promising strategy to enhance the optical properties; however, the development of boron-doped helical systems featuring tunable emission, high configurational stability, and strong chiroptical response has been limited by synthetic challenges. We report the chemistry of bora[7]helicene and its dimeric diborahelicate. While the dimeric form is thermodynamically favored in the haloborane precursor, saturation of the boron coordination sphere by exogenous carbene or carbone ligands induces monomerization, reverting the structure to the bora[7]helicene. By employing a variety of ligands, late-stage structural diversification was achieved, yielding the first examples of cationic boron helices, which show exceptional emission tunability across the entire visible spectrum, and chiroptical responses surpassing those of previously reported [7]helicenes. Theoretical studies indicate that the double-helix geometry and the intramolecular charge transfer play a significant role in achieving high dissymmetry factors. Show less

Transition-metal acyclic carbene complexes have received increasing attention in recent years. As acyclic carbene ligands show strong σ-donating properties comparable to N-heterocyclic carbene (NHC) ligands, transition-metal complexes with acyclic carbene ligands also demonstrate outstanding performance and functional properties similar to their NHC counterparts. Therefore, transition-metal acyclic carbene complexes are considered viable alternatives to NHC complexes in the development of metal-based functional materials. As transition-metal acyclic carbene complexes can be prepared from metal isocyanide synthetic precursors, substituents of different electronic and steric natures as well as functional moieties can be readily introduced into acyclic carbene ligands by changing the isocyanide ligand. Moreover, the open structure of acyclic carbene ligands has made their structure and the electronic properties strongly dependent on the substituents as well as the micro-environment. As a result, the functional properties of acyclic complexes can be drastically varied by rational molecular design of the ligands. The environmental sensitivity of the properties of these complexes also made them ideal for the development of stimuli-responsive materials and chemical sensors. In this article, the preparation, electronic properties and design of metal acyclic carbene complexes with different functional properties for the development of advanced materials are described. Show less

AbstractTwo mononuclear protic ferrocenyl acyclic diamino carbene gold(I) complexes AuCl[C(NHFc)(NR2)] were prepared by nucleophilic attack of diethylamine (R = Et) and diisopropylamine (R = iPr) at the ferrocenyl substituted isocyanide complex chlorido(isocyanoferrocene)gold(I) AuCl(CN−Fc). In the solid state, the multifunctional protic carbene gold(I) complexes display intermolecular aurophilic interactions or intermolecular NH⋅⋅⋅Cl hydrogen bonding in addition to intramolecular non‐classical NH⋅⋅⋅Fe hydrogen bonds. Oxidation of the AuCl[C(NHFc)(NR2)] complexes initially takes place at the iron centres giving highly coloured ferrocenium ions, which subsequently likely undergo electron transfer from gold(I) to iron(III) yielding putative EPR‐active gold(II) species. Show less

Acyclic diamino carbenes (ADCs) are interesting alternatives to their more widely studied N-heterocyclic carbene counterparts, particularly due to their greater synthetic accessibility and properties such as increased sigma donation and structural flexibility. ADC gold complexes are typically obtained through the reaction of equimolar amounts of primary/secondary amines on gold-coordinated isocyanide ligands. As such, the reaction of diamine nucleophiles to isocyanide gold complexes was expected to lead to bis-ADC gold compounds with potential applications in catalysis or as novel precursors for gold nanomaterials. However, the reaction of primary diamines with two equivalents of isocyanide gold chlorides resulted in only one of the amine groups reacting with the isocyanide carbon. The resulting ADC gold complexes bearing free amines dimerized via coordination of the amine to the partner gold atom, resulting in cyclic, dimeric gold complexes. In contrast, when secondary diamines were used, both amines reacted with an isocyanide carbon, leading to the expected bis-ADC gold complexes. Density functional theory calculations were performed to elucidate the differences in the reactivities between primary and secondary diamines. It was found that the primary amines were associated with higher reaction barriers than the secondary amines and hence slower reaction rates, with the formation of the second carbenes in the bis-ADC compounds being inhibitingly slow. It was also found that diamines have a unique reactivity due to the second amine serving as an internal proton shuttle. Show less

A library of 14 heterobis(carbene) complexes of the general formula [Au(ⁱPr₂-bimy)(ADC)]BF₄ (7-20) containing the N-heterocyclic carbene reporter ⁱPr₂-bimy and various protic acyclic diaminocarbenes (ADCs) have been prepared to estimate their stereoelectronic properties by ¹³C NMR spectroscopy and percentage buried volume (%V_bur) determinations. Their preparation was achieved by nucleophilic attack of five secondary amines on six mixed NHC/isocyanide complexes of the type [Au(ⁱPr₂-bimy)(CN-R)]BF₄ (1-6). Analyses of the ⁱPr₂-bimy carbene signals reveal that protic ADCs are stronger donors than classical and expanded-ring NHCs. On the other hand, they are weaker donating compared to NHCs with reduced-heteroatom stabilization. Moreover, stereoelectronic fine-tuning of these ligands is possible by a diverse range of substituents originating from the employed isocyanides and amines. Show less

A series of gold(I) and gold(III) N‐acyclic diamino carbene (ADC) complexes with different ancillary ligands have been synthesized. The chloride carbene derivatives [Au{C(NHR)(NHCH2py)}Cl] (R = Cy, R = naphthyl, R = xylyl) have been obtained by reaction of 2‐picolylamine with the corresponding [AuCl(CNR)]. The gold(I) thiolate derivatives [Au{C(NHR)(NHCH2py)}(Spy)] were prepared by reaction of the chlorido complexes with 2‐mercaptopyridine (2‐HSpy) in presence of potassium carbonate. The phosphane derivative [Au(pyCH2NH2)(PPh3)](OTf) was obtained by reaction of freshly prepared [Au(OTf)(PPh3)] with 2‐picolylamine. The phosphane‐carbene complexes [Au{C(NHR)(NHCH2py}(PPh3)](OTf) were obtained from the reaction of picolylamino species with the isocyanide. The gold(III) derivative cis‐[Au(C6F5)2(pyCH2NH2)](ClO4) was obtained by the reaction of 2‐picolylamine with freshly [Au(C6F5)2(Et2O)2](ClO4). The reaction of the former with CNCy led to complex cis‐[Au(C6F5)2{C(NHCy)(NHCH2py)}]ClO4 by a nucleophilic attack of the isocyanide to the amine ligand, thus producing a bidentate C,N acyclic carbene ligand. Cytotoxic studies against the tumor human cell lines Jurkat (T‐cell leukaemia), MiaPaca2 (pancreatic carcinoma), A549 (lung carcinoma) and MDA‐MB‐231 (breast carcinoma) showed moderate to good cytotoxic activity for some of the complexes. Show less

Mononuclear gold(I) acyclic diaminocarbenes (ADCs) were prepared by the reaction of 1,2-cyclohexanediamine with the corresponding isocyanide complexes [AuCl(CNR)] (R = Cy, ^t Bu). The three-component coupling of aldehydes, amines, and alkynes was investigated by using these gold(I) ADC complexes. The new gold(I) metal complexes are highly efficient catalysts for the synthesis of propargylamines and indolizines in the absence of solvent and in mild conditions. This method affords the corresponding final products with excellent yields in short reaction times. Additionally, chiral gold(I) complexes with ADCs have been prepared and tried in the enantioselective synthesis of propargylamines. Show less

No cycle required: The straightforward synthesis of acyclic (amino)(ylide)carbene gold complexes was achieved by reaction of isocyanide gold complexes with phosphorus and arsenic ylides as well as electron-rich olefins. Their ability to form bimetallic species and to act as ligand-transfer reagents has also been established. Show less

The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell lines were evaluated in vitro using a systematic screening strategy. Initially all compounds were tested against a panel of 12 human tumor cell lines, and the best performers were tested against a larger 36-cell-line panel. Very pronounced antiproliferative properties were highlighted in most cases, with cytotoxic potencies commonly falling in the low micromolar--and even nanomolar--range. Overall, good-to-excellent tumor selectivity was established for at least seven compounds, making them particularly attractive for further pharmacological evaluation. Compare analysis suggested that the observed antiproliferative effects are caused by a variety of molecular mechanisms, in most cases "DNA-independent," and completely different from those of platinum drugs. Remarkably, some new biomolecular systems such as histone deacetylase, protein kinase C/staurosporine, mammalian target of rapamycin/rapamycin, and cyclin-dependent kinases were proposed for the first time as likely biochemical targets for the gold(III) species investigated. The results conclusively qualify gold(III) compounds as a promising class of cytotoxic agents, of outstanding interest for cancer treatment, while providing initial insight into their modes of action. Show less