Gold(I) complexes bearing P-pyrrole phosphine ligands: Synthesis and catalytic activity towards cycloisomerization of 1,6-enynes

P-pyrrole phosphines (R₂Ppyr), in which a pyrrole group is directly bonded to the phosphorus atom, act as monodentate k-P ligands towards gold(I) center to afford either neutral or cationic mononuclear complexes as well as neutral dinuclear complexes. All of these new gold(I) complexes have been structurally characterized and their first uses in catalysis have demonstrated their effectiveness as precatalysts for the enyne cycloisomerization reactions.     

Dinuclear gold(I)-N-heterocyclic carbene complexes: Synthesis,characterization, and catalytic application for hydrohydrazidation of terminal alkynes

Dinuclear gold(I)-N-heterocyclic carbene complexes were developed for the hydrohydrazidation of terminal alkynes. The gold(I)-N-heterocyclic carbene complexes 2a-2b were synthesized in good yields from silver complexes synthesized in situ, which in turn were obtained from the corresponding imidazolium salts with Ag₂O in dichloromethane as a solvent. The new air-stable gold(I)-NHC complexes, 2a - 2b, were characterized using NMR spectroscopy, elemental analysis, infrared, and mass spectroscopy studies. The gold(I) complex 2a was characterized using X-ray crystallography. Bis-N-heterocyclic carbene–based gold(I) complexes 2a - 2b exhibited excellent catalytic activities for hydrohydrazidation of terminal alkynes yielding acylhydrazone derivatives. The working catalytic system can be used in gram-scale synthesis. In addition, the catalytic reaction mechanism of the hydrohydrazidation of terminal alkynes by gold(I)-NHC complex was studied in detail using density functional theory.     

Dinuclear gold(I) Complexes with Bidentate NHC Ligands as Precursors for Alkynyl Complexes via Mechanochemistry

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)₂]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)₂] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.     

Inclusion Complexes of Gold(I)-Dithiocarbamates with β-Cyclodextrin: A Journey from Drug Repurposing towards Drug Discovery

The gold(I)-dithiocarbamate (dtc) complex [Au(N,N-diethyl)dtc]₂ was identified as the active cytotoxic agent in the combination treatment of sodium aurothiomalate and disulfiram on a panel of cancer cell lines. In addition to demonstrating pronounced differential cytotoxicity to these cell lines, the gold complex showed no cross-resistance in therapy-surviving cancer cells. In the course of a medicinal chemistry campaign on this class of poorly soluble gold(I)-dtc complexes, >35 derivatives were synthesized and X-ray crystallography was used to examine structural aspects of the dtc moiety. A group of hydroxy-substituted complexes has an improved solubility profile, and it was found that these complexes form 2 : 1 host–guest inclusion complexes with β-cyclodextrin (CD), exhibiting a rarely observed “tail-to-tail” arrangement of the CD cones. Formulation of a hydroxy-substituted gold(I)-dtc complex with excess sulfobutylether-β-CD prevents the induction of mitochondrial reactive oxygen species, which is a major burden in the development of metallodrugs.     

Constrained digold(I) diaryls: syntheses, crystal structures, and photophysics

A series of di(gold(I) aryls), L(AuR)(2) (L = DPEphos, DBFphos, or Xantphos; R = 1-naphthyl, 2-naphthyl, 9-phenanthryl, or 1-pyrenyl), have been prepared. The complexes were characterized by multinuclear NMR spectroscopy, static and time-dependent optical spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. In addition, DFT calculations on model dinuclear gold complexes have been used to examine the electronic structures. Photophysical properties of the dinuclear complexes have been compared to mononuclear analogues. Low-temperature excited-state lifetimes for both the mononuclear and dinuclear complexes in toluene indicate triplet-state emission. Time-resolved DFT calculations suggest that emission originates from aryl-ligand transitions, even if the LUMO resides elsewhere.     

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Several gold(I) complexes with cysteine‐containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc₂O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh₃)] gives the gold‐dipeptide‐phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR₃)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non‐proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC₅₀ values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents.     

The Quest for Mononuclear Gold(II) and Its Potential Role in Photocatalysis and Drug Action

The chemistry of gold strongly focuses on the ubiquitous oxidation states +I and +III. The intermediate oxidation state +II is generally avoided in mononuclear gold species. In recent years, gold(II) has been increasingly suggested as a key intermediate in artificial photosynthesis systems, with gold(III) moieties acting as electron acceptors, as well as in gold‐catalyzed photoredox catalysis and radical chemistry. This Minireview provides a concise summary of confirmed and characterized mononuclear open‐shell gold(II) complexes. Recent findings on structural motifs and reactivity patterns will be discussed. Exciting developments in the fields of photosynthesis, photocatalysis, and potential roles in medicinal chemistry will be outlined.     

Direct Observation of Aryl Gold(I) Carbenes that Undergo Cyclopropanation,C−H Insertion,and Dimerization Reactions

Mesityl gold(I) carbenes lacking heteroatom stabilization or shielding ancillary ligands have been generated and spectroscopically characterized from chloro(mesityl)methylgold(I) carbenoids bearing JohnPhos‐type ligands by chloride abstraction with GaCl₃. The aryl carbenes react with PPh₃ and alkenes to give stable phosphonium ylides and cyclopropanes, respectively. Oxidation with pyridine N‐oxide and intermolecular C?H insertion to cyclohexane have also been observed. In the absence of nucleophiles, a bimolecular reaction, similar to that observed for other metal carbenes, leads to a symmetrical alkene.     

Direct Observation of Aryl Gold(I) Carbenes that Undergo Cyclopropanation,C−H Insertion,and Dimerization Reactions

Mesityl gold(I) carbenes lacking heteroatom stabilization or shielding ancillary ligands have been generated and spectroscopically characterized from chloro(mesityl)methylgold(I) carbenoids bearing JohnPhos‐type ligands by chloride abstraction with GaCl₃. The aryl carbenes react with PPh₃ and alkenes to give stable phosphonium ylides and cyclopropanes, respectively. Oxidation with pyridine N‐oxide and intermolecular C?H insertion to cyclohexane have also been observed. In the absence of nucleophiles, a bimolecular reaction, similar to that observed for other metal carbenes, leads to a symmetrical alkene.     

Effective Control of the Electron-donating Ability of Phosphines by using Phosphazenyl and Phosphoniumylidyl Substituents

Phosphoniumylidyl and phosphazenyl groups are effective substituents to increase the electron-donating ability of tertiary phosphines. However, the influence of structural variations among those substituents on the electronic properties of the phosphines is little explored. Herein, we show that protonation of the ylidic carbon atom of phosphoniumylidyl phosphines increases the Tolman electronic parameter (TEP) by ΔTEP = 16.0–18.8 cm^–1. Furthermore, phosphazenyl phosphines were synthesized with isopropyl groups (NP{iPr}₃) and tetramethylguanidino groups (NP{tmg}₃) at the phosphonium center. Determination of their TEP values reveals a remarkable low substituent parameter of χ = –18.5 cm^–1 for the NP(tmg)₃ group. In addition, we prepared the corresponding gold(I) complexes and determined their solid-state structures using single-crystal X-ray diffraction studies to analyze the steric profile of the new phosphine ligands.     

氮杂环卡宾双核金络合物催化的胺芳基化反应

联萘胺出发合成了氮杂环卡宾双核和单核金络合物, 通过X射线的单晶衍射确定了它们的结构, 并将其应用于催化胺芳基化反应中, 以高达95%的收率得到吡咯烷类化合物. 综合上述实验结果, 发现氮杂环卡宾双核金络合物4b中存在着Au(I)-Au(I)间相互弱作用力, 而且这种弱相互作用可能对该催化反应起重要的作用, 以高收率得到吡咯烷类化合物.     

Synthesis, 13C NMR and IR spectroscopic studies of gold(I) complexes of imidazolidine-2-thione and its derivatives

The gold(I) complexes of imidazolidine-2-thione and its derivatives were synthesized and their ¹³C NMR and IR spectroscopic studies were carried out. When gold(III) was reacted with the ligands using a 1:4 metal to ligand ratio, gold(III) was reduced to gold(I), the bis complexes of the general formula AuL_nX (where n = 2) were formed. However, when gold(III) was reduced to gold(I) by a reducing agent followed by an addition of the ligand to an aqueous or methanolic solution of gold(I), only mono complexes of the type AuLX were obtained. The structures of the reported complexes are proposed on the basis of their spectroscopic measurements.     

Geminally Diaurated Aryls Bridged by Semirigid Phosphine Pillars: Syntheses and Electronic Structure

Geminally diaurated μ₂‐aryl complexes have been prepared where gold(I) centers were bridged by the semirigid diphosphine ligands bis(2‐diphenylphosphinophenyl)ether (DPEphos) and 4,6‐bis(diphenylphosphanyl)dibenzo[b,d]furan (DBFphos). Diaurated complexes were synthesized in ligand redistribution reactions of the corresponding di‐gold dichlorides with di‐gold diaryls (six of them new) and silver(I) salts. Diaurated complexes were isolated as salts of the minimally coordinating anions SbF₆^? and ReO₄^?. Efforts to prepare salts of the tetraarylborate [B(3,5‐(CF₃)₂C₆H₃)₄]^? led to transmetalation from boron, with crystallization of the fluorinated aryl complex. The new complexes were characterized by multinuclear NMR, absorption and emission spectroscopies, 77 K emission lifetimes, and by combustion analysis; three are crystallographically characterized. Structures of geminally diaurated aryl ligands are compared to those of mono‐aurated analogues. Both crystal structures and density‐functional theory calculations indicate slight but observable disruptions of aryl ligand aromaticity by geminal di‐gold binding. An intermolecular aurophilic interaction in one structurally authenticated complex was examined computationally.     

Yldiide Ligands as Building Blocks for Polynuclear Coinage Metal Complexes: Metal Squares,Triangles and Chains

Yldiides have unique electronic properties and donor abilities, but as ligands in transition metal complexes they are scarcely represented in the literature. Here, the controlled synthesis of a series of polynuclear gold yldiide complexes derived from triphenyl(cyanomethyl)phosphonium bromide, [Ph₃PCH₂CN]Br, under mild conditions is described. Anionic dinuclear NBu₄[(AuX)₂{C(CN)PPh₃}] (X=Cl, C₆F₅) or trinuclear derivatives NBu₄[Au₃X₂{C(CN)PPh₃}] bearing terminal chloride or pentafluorophenyl groups and bridging yldiide ligands have been prepared. These compounds evolve in solution giving rise to the formation of an unprecedented tetrameric gold cluster, [Au₄{C(CN)PPh₃}₄], by the loss of the gold complex NBu₄[AuX₂]. This gold cluster can also be prepared in high yield by a transmetalation reaction from the analogous tetrameric silver cluster, and two geometric isomers have been characterised, their formation dependent on the synthetic route. The triphenylphosphonium cyanomethyldiide ligand has also been used to build different dinuclear and trinuclear cationic complexes bearing phosphine or diphosphine ancillary ligands and bridging yldiide moieties. Further coordination through the cyano group of the yldiide ligand gives heterometallic trinuclear or pentanuclear derivatives. Structural characterisation of many of these compounds reveals the presence of complex molecular systems stabilised by gold⋅⋅⋅gold interactions and bridging yldiide ligands.     

Development of versatile and silver-free protocols for gold(I) catalysis

The use of a versatile N‐heterocyclic carbene (NHC) gold(I) hydroxide precatalyst, [Au(OH)(IPr)], (IPr=N,N′‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) permits the in situ generation of the [Au(IPr)]⁺ ion by simple addition of a Brønsted acid. This cationic entity is believed to be the active species in numerous catalytic reactions. ¹H NMR studies in several solvent media of the in situ generation of this [Au(IPr)]⁺ ion also reveal the formation of a dinuclear gold hydroxide intermediate [{Au(IPr)}₂(μ‐OH)], which is fully characterized and was tested in gold(I) catalysis.     

Structure of copper 4-(n,n- dimethylamino)pyridine complexes and their catalytic activity in the oxidative coupling of 2,6-dimethylphenol

The oxidative coupling of 2,6-dimethylphenol (DMP) by copper complexes of 4-(N,N)-dimethylamino)pyridine (DMAP) has been studied. Catalytic experiments were carried out in which the DMAP-to-copper ratio and the amount and nature of the copper counter ions were varied. Supporting UV and EPR experiments were performed, and it was concluded that both dinuclear and mononuclear complexes are catalytically active, the mononuclear species being the more active. In solution both species are in equilibrium with one another. The mono/di ratio can be increased by addition of extra DMAP ligands. An excess of coordinating counter-ions increases the amount of dinuclear species. However, a few coordinating counterions are inevitable, and the catalytically most active species was found to be ‘Cu(DMAP)₄Cl(OH)’, the role of Cl⁻ probably being that of a bridging counter-ion promoting the formation of dinuclear Cu(I) complexes for the reoxidation step. The DMAP ligands are coordinated to Cu(II) through the pyridine N-atoms, as was determined by X-ray analysis. The Cu(II)DMAP complexes are catalytically active even without initial hydroxide addition. It is believed that the strongly basic DMAP ligands produce some hydroxide from traces of water present in the reaction medium. The species ‘Cu(DMAP)₄Cl(OH)’ proved to be able to produce relatively high molecular weight polyphenylene oxide (PPO) in short time and with good specificity ( >95%).     

The Impact of Crystal Packing and Aurophilic Interactions on the Luminescence Properties in Polymorphs and Solvate of Aroylacetylide–Gold(I) Complexes

The influence of the chemical substitution, crystal packing, and aurophilic interactions of the gold(I) acetylide complexes of the type (ArCOC≡C)_nAuPEt₃ (n=1,2) on their luminescent properties were examined. All described complexes undergo ligand scrambling in solution, which results in the formation of stable, easily isolated crystals that contain [ArCO(C≡C)_n]₂Au⁻(Et₃P)₂Au⁺ homoleptic species. In particular, we observed that the (benzoylacetylide)gold(I) complex yields three crystal forms with strikingly different luminescence properties. We monitored the conversion pathway for these forms: an orange luminescent form of homoleptic complex upon drying undergoes spontaneous transformation to bright green fluorescent form and finally to the weakly blue emissive one. In addition, we report a rare example of a helical arrangement of Au⋅Au⋅Au chains that are observed for the first time in acetylide gold(I) complexes in the case of heteroleptic (benzoylacetylide)gold(I) complex. This is a very rare case in which crystal structures and ensuing electronic properties of the heteroleptic and Au^I complexes could be directly compared.     

Gold Ion–Angiotensin Peptide Interaction by Mass Spectrometry

Stimulated by the interest in developing gold compounds for treating cancer, gold ion–angiotensin peptide interactions are investigated by mass spectrometry. Under the experimental conditions used, the majority of gold ion–angiotensin peptide complexes contain gold in the oxidation states I and III. Both ESI-MS and MALDI-TOF MS detect singly/multiply charged ions for mononuclear/multinuclear gold-attached peptides, which are represented as [peptide + a Au(I) + b Au(III) + (e - a -3b) H]^e+, where a,b ≥ 0 and e is charge. ESI-MS data shows singly/multiply charged ions of Au(I)-peptide and Au(III)-peptide complexes. This study reveals that MALDI-TOF MS mainly detects singly charged Au(I)-peptide complexes, presumably due to the ionization process. The electrons in the MALDI plume seem to efficiently reduce Au(III) to Au(I). MALDI also tends to enhance the higher polymeric forms of gold-peptide complexes regardless of the laser power used. Collision-induced dissociation experiments of the mononuclear and dinuclear gold-attached peptide ions for angiotensin peptides show that the gold ion (a soft acid) binding sites are in the vicinity of Cys (a soft ligand), His (a major anchor of peptide for metal ion chelation), and the basic residue Arg. Data also suggests that the abundance of gold-attached peptides increases with higher gold concentration until saturation, after which an increase in gold ion concentration leads to the aggregation and/or precipitation of gold-bound peptides.     

Phosphino-(α-sulfinylalkyl)phosphonium ylide complexes (Rh,Pd) with a configurationally stable asymmetric ylidic carbon

The synthesis and structure of Rh(I) and Pd(II) complexes of chiral P,C-chelating phosphino-(α-sulfinylalkyl)phosphonium ylide ligands with a trisubstituted asymmetric ylidic center P⁺–C1R(S1(O)p-Tol)–M (R = alkyl group) have been investigated, and compared to those of the analogous disubstituted ylide complexes (R = H). Reaction of the ethyl onium ylide of o-bis(diphenylphosphino)benzene with (?)-menthyl-(S)-p-tolylsulfinate afforded the corresponding racemic erythro phosphino-(α-sulfinylethyl)phosphonium in 90% de (R = Me). The racemization process is interpreted by a Berry-like pseudorotation mechanism driven by the steric repulsion between the α-methyl substituent and the bulky menthyloxy S-substituent or sulfur lone pair in the intermediate ylide-sulfinyl adduct. The ylide of phosphino-(α-sulfinylethyl)phosphonium reacts with [Rh(cod)₂][PF₆] and PdCl₂(MeCN)₂ to afford the corresponding P,C1-chelated threo-Rh(I) and erythro-Pd(II) mononuclear complexes in 70% yield and total diastereoselectivity. These respective complexes act as efficient catalytic precursors for the hydrogenation of (Z)-α-acetamidocinnamic acid and allylic substitution of 3-acetoxy-1,3-diphenyl-1-propene with sodium dimethyl malonate. The bonding features of the erythro-Pd(II) complex exhibiting a sulfinyl O?Pd interaction are studied theoretically at the DFT level using ELF and MESP analyses. The η²-P,C haptomeric form of the ylide ligand is estimated to compete at 19% with the η¹-C haptomeric form dominating at 81%.     

Synthesis of New Phosphonium Ylides Containing Thiophene and Furan Rings and Study of Their Reaction with Mercury(II) Halides: Spectral and Structural Characterization

Reactions of phosphonium ylides (4‐MeC₆H₄)₃PCHC(?O)(2‐C₄H₃S) (tptpy), Ph₃PCHC(?O)(2‐C₄H₃O) (fppy), and (4‐MeC₆H₄)₃PCHC(?O)(4‐BrC₆H₄) (bbtppy) with HgX₂ (X=Cl, Br, and I) in equimolar ratios in MeOH as solvent leads to the binuclear products 1 – 3 (Scheme 1). The bridge‐splitting reaction of the binuclear complex [{HgI₂(bbtppy)}₂] ( 3c ) by DMSO yields the mononuclear complex [HgI₂?(bbtppy) (DMSO)] ( 3d ) (Scheme 2). This bridge‐splitting reaction can also be a method for the synthesis of mononuclear products. C‐Coordination of the ylide and O‐coordination of DMSO are demonstrated by a single‐crystal X‐ray‐analysis of the mononuclear complex 3d . Characterization of the obtained compounds was also performed by means of elemental analysis and IR and ¹H‐, ³¹P‐, and ¹³C‐NMR spectroscopy. A theoretical study of some Hg^II complexes with phosphonium ylides is also reported.