Diaminocarbene Complexes Research Articles

Luminescent Cyclometalated Platinum Acyclic Diaminocarbene Complexes as PhOLED Dopants

Luminescent Cyclometalated Platinum Acyclic Diaminocarbene Complexes as PhOLED Dopants

Metal-(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple-Negative Breast Cancer.

Invited for the cover of this issue are Tatiyana Serebryanskaya, Mikhail Kinzhalov and co-workers at St. Petersburg State University, the Research Institute for Physical Chemical Problems, Belarusian State University, Togliatti State University and Blokhin National Medical Research Center of Oncology. The image depicts the shield of Pallas Athena with the structure of a palladium carbene complex that protects against triple-negative breast cancer. Read the full text of the article at 10.1002/chem.202400101.

Front Cover: Metal‐(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple‐Negative Breast Cancer (Chem. Eur. J. 28/2024)

Front Cover: Metal‐(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple‐Negative Breast Cancer (Chem. Eur. J. 28/2024)

Metal-(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple-Negative Breast Cancer.

Hydrolytically stable PdII and PtII complexes supported by acyclic diaminocarbene ligands represent a novel class of structural organometallic anticancer agents exhibiting nanomolar antiproliferative activity in a panel of cancer cell lines (IC50 0.07-0.81 μM) and up to 300-fold selectivity for cancer cells over normal primary fibroblasts. The lead drug candidate was 300 times more potent than cisplatin in vitro and showed higher efficacy in reducing the growth of aggressive MDA-MB-231 xenograft tumors in mice.

Synthesis and reactivity of air stable Ni(II) complexes with isocyanides and dialkyldithiophosphate ligands: acyclic diaminocarbene formation.

A library of new neutral and cationic Ni(II) complexes containing isocyanide ligands and mono- or dialkyl-dithiophosphate have been easily prepared and fully characterized. The synthesis of the neutral complexes unfolds through the alkyl transfer from one alkyldithiophosphate leaving group coordinated to the Ni(II) complex. The alkyl transfer is controlled by steric factors and is highly solvent-dependent. These complexes shown to constitute excellent precursors to obtain new families of air stable Ni(II)-based acyclic diaminocarbene complexes (Ni(II)-ADCs) by nucleophilic attack with various alkyl-substituted amines. Remarkably, the ADC is only produced at one of the isocyanide ligands, keeping the other isocyanide unreacted. This was subsequently exploited to prepare the unprecedented neutral and cationic dinuclear Ni(II) complexes containing a bridging bis-carbene ligand using piperazine.

Luminescent Platinum Complexes with π-Extended Aryl Acetylide Ligands Supported by Isocyanides or Acyclic Diaminocarbenes.

In this work, we present a series of luminescent platinum acetylide complexes with acetylides that are electronically modified and/or π-extended. Six isocyanide-supported complexes with the general formula cis-[Pt(CNAr)2(C≡CR)2] and six acyclic diaminocarbene (ADC) complexes of the form trans-[Pt(ADC)2(C≡CR)2], all using the same five acetylide ligands, are described. The compounds are characterized by multinuclear NMR, FT-IR, and single-crystal X-ray diffraction. In most cases, the phosphorescence arises from an acetylide-centered 3(π → π*) excited state, although in one of the isocyanide compounds there is evidence for a charge-transfer excited state. The photoluminescence wavelength depends strongly on the substitution pattern and extent of the π conjugation on the acetylide, with maxima spanning the range of ca. 460-540 nm. Most photoluminescence lifetimes are long, beyond 50 μs, and quantum yields are low to moderate, 0.043-0.27. The photoluminescence quantum yields and lifetimes in these compounds do not systematically improve in the ADC complexes compared to the isocyanide versions, suggesting the neutral ligand σ-donor character does not play a large role in the excited-state dynamics when the triplet excited state is delocalized over a large π system.

Synthesis of gold(I) diaminocarbene complexes by the addition of amines across coordinated isocyanoferrocene

Gold(I) acyclic diaminocarbene complexes of the [AuCl{C(NHFc)(NR2)}] type (Fc = ferrocenyl) were conveniently synthesized by a one-pot procedure. In this method, 1 equiv. of isocyanoferrocene (FcNC) and an excess of primary or secondary amines R2NH (dimethylamine, morpholine, methylamine, cyclohexylamine, and p-toluidine) are sequentially added to [AuCl(SMe2)] as a gold source in dichloromethane. The stepwise synthesis, in which [AuCl(FcNC)] is the isolated intermediate, worked equally well but generated lower overall yields due to compound loss during the two purification steps. The approach was further extended to synthesize the corresponding cationic biscarbene complexes [Au{C(NHFc)(NR2)}2]Cl simply by using 2 equiv. of FcNC during the “first” reaction step. The compounds form conformational isomers in solution that differ by the orientation of substituents at the carbene units. Based on DFT calculations, these isomers exhibit similar energies (energy difference ≤ 5 kcal mol–1). The crystal structures revealed symmetrical carbene units and the dominant role of the N-H⋅⋅⋅Cl interactions in the crystal assemblies in all cases, which also control the tendency for a particular conformation in the solid state.

Acyclic diaminocarbenes (ADCs) and their catalytic activity in metal catalysed organic transformation reactions

Abstract Acyclic diaminocarbenes (ADCs)–Metal complex having strong donor ability and thermal stability led to extensive usability across every area of inorganic and organometallic chemistry. The unique properties of acyclic diaminocarbenes (ADCs) provide certain advantages over other carbene ligands and have the potential to make a great impact in catalysis. Further, the straightforward synthesis of M–ADCs (metal bound acyclic diaminocarbenes) complexes via metal-mediated reaction provides a wide range of well-defined metal carbene catalysts, which might inspire more researchers to devise unsymmetrically substituted, chiral, and novel acyclic carbene compounds. Although the above synthetic route is limited to a few late transition metals, but have great opportunities to expand the scope of this method. The application of M–ADCs complexes as a catalyst for several organic transformation reactions such as various cross-coupling reactions and asymmetric synthesis like hydroarylation, hydroazidation, hydroamination, cyclization and addition reactions which have shown comparable or even higher activities than the analogous M–NHCs based on all the reports presented. Recent findings of donor ability of several ADC ligands would be useful in fine-tuning the electronic properties, and then a catalyst with a certain combination of donicity and steric requirement could open new doors in catalytic reactivity. Thus, the objective of this review is to assess the recent growths that have been made in designing novel and chiral ADCs ligands and synthesizing ADCs–Metal complexes and to highlight catalytic activities of metal acyclic diaminocarbene complexes for cross-coupling reactions.

Publisher's Note

Publisher's Note

Molecular Switching through Chalcogen-Bond-Induced Isomerization of Binuclear (Diaminocarbene)PdII Complexes

Binuclear diaminocarbene complexes, which form as a regioisomer mixture in the reaction between isocyanide–palladium(II) complex cis-[PdCl2(CNXyl)2] and 1,3-thiazol-2-amine, are able to exchange an anionic chloride ligand with other halides, such as Br or I. This process also affords binuclear complexes as mixtures of kinetically and thermodynamically controlled regioisomers. In CDCl3 solutions, we observed interconversion of kinetically and thermodynamically controlled regioisomers. The results of the DFT calculations revealed that in CHCl3 solution, each pair of the isomers exhibited two different types of chalcogen bonding such as S···X or S···N; the presence of CBs for two complexes in the solid state was also proven through X-ray crystallographic study. Based on the combined experimental and theoretical data, it could be concluded that thermodynamic favorability for the formation of thermodynamically controlled regioisomers increases in the Cl < Br ≈ I row and correlate well with the energy difference between S···N and S···X (X = Cl, Br, I) chalcogen bonds in kinetically and thermodynamically controlled products. This means that it is possible to change the structure of metallocycles in binuclear diaminocarbene complexes by simply replacing one halide ligand with another.

Palladium(II) and Platinum(II) Deprotonated Diaminocarbene Complexes Based on N-(2-Pyridyl)ureas with Oxadiazole Periphery

Metal mediated coupling of isocyanides with substituted N-(pyridine-2-yl) ureas was first used to incorporate privileged biological motifs into platinum metal complexes. We synthesized two palladium(II) and two platinum(II) cyclometallated species with oxadiazole cores. The compounds were isolated in good yields (61–73%) and characterized by high-resolution mass spectrometry and 1H, 13C, and 195Pt NMR spectroscopies. The structures of three complexes were additionally elucidated by X-ray diffraction analysis. These complexes indeed showed cytotoxic activity. The species bearing the 1,3,4-oxadiazole moiety exhibit more potency than the ones with the 1,2,4-oxadiazole ring. Particularly, the cytotoxic effect of both 1,3,4-oxadiazole-based complexes towards T98G cells significantly exceeds the common antitumor metal-drug cisplatin.

Pyridine‐2(1H)‐thione as a Bifunctional Nucleophile in Reaction with PdII and PtII Aryl Isocyanide Complexes

AbstractA method for obtaining C,S‐cyclometalated deprotonated diaminocarbene complexes via the addition of a bifunctional N,S‐nucleophile's endocyclic nitrogen atom to a coordinated isocyanide has been extended to the reactions with pyridine‐2(1H)‐thione. The coupling of PdII‐ and PtII‐bis(arylisocyanide) complexes with pyridine‐2(1H)‐thione leads to the formation of mononuclear C,S‐cyclometalated deprotonated diaminocarbene complexes in 90–96 % yield. The reaction proceeds via the initial coordination of the thione sulfur atom to the metal center followed by the intramolecular nucleophilic addition of the heterocyclic nitrogen atom to the metal‐ligated isocyanide carbon. Using an excess of pyridine‐2(1H)‐thione in this reaction leads to the formation of a mono‐C,S‐cyclometalated complex with a pendant mercaptopyridine ligand which is involved in the reversible intramolecular nucleophilic addition of the pyridine nitrogen to the isocyano carbon. The obtained complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies, and single‐crystal X‐ray diffraction.

An Acyclic Diaminocarbene Complex of Platinum Formed by Desulfurization of 1,3‐Bis(3‐methylpyridin‐2‐yl)thiourea

AbstractThe reaction of the ambidentate ligand 1,3‐bis(3‐methylpyridin‐2‐yl)thiourea (1) with [PtCl2(dmso)2] in dichloromethane led to formation of a poorly soluble compound 2, characterized as a conventional chelate complex [PtCl2(1)]=2. Reaction in methanol resulted in desulfurization to produce a fluorescing cationic diaminocarbene−platinum(II) complex 3, the structure of which was elucidated by X‐ray crystallography, mass spectrometry and NMR. Experimental findings were supported by DFT calculations.

Diaminocarbene Complexes of Palladium(II) Containing 2-Aminooxazole and 2-Aminothiazole Heterocyclic Ligands as Potential Antitumor Agents

Diaminocarbene Complexes of Palladium(II) Containing 2-Aminooxazole and 2-Aminothiazole Heterocyclic Ligands as Potential Antitumor Agents

Highly Sterically Encumbered Gold Acyclic Diaminocarbene Complexes: Overriding Electronic Control in Regiodivergent Gold Catalysis

Two series of sterically encumbered gold(I) acyclic diaminocarbene (ADC) complexes were prepared by reaction of mono- and dialkylamines with gold-bound 2-mesitylphenyl isocyanide (monomesityl serie...

The carbene transfer to strong Lewis acids: copper is better than silver.

A new convenient approach to the synthesis of useful N-heterocyclic carbene complexes of group 13 metals was successfully developed. We demonstrate that air-stable copper(i) diaminocarbene complexes are excellent carbene transfer reagents for the synthesis of (IMes or IPr)MCl3 with high yields (M = Al, Ga). Use of this simple method allowed for the first time to obtain (IPr)AlCl3, inaccessible via a free carbene route. In contrast to copper complexes, under the same conditions the more commonly used silver analog (IPr)AgCl reacts with MCl3 (M = Al, Ga, In) yielding only the homoleptic cationic complexes [(IPr)2Ag]+MCl4-.

Effect of the Structure of C,N-Chelate Diaminocarbene Palladium(II) Complexes on Their Catalytic Activity in the Sonogashira Reaction

The catalytic activity of C,N-chelate diaminocarbene palladium(II) complexes containing a 3,4-diaryl-1H-pyrrol-2,5-diimine fragment in a copper-free Sonogashira reaction was studied. Reactions catalyzed by C,N-chelate diaminocarbene palladium(II) complexes do not require preliminary degassing, since such catalysts are air- and moisture-stable. In this work, comparative analysis of the catalytic activity of two types of C,N-chelate diaminocarbene complexes containing, along with the diaminocarbene ligand, isonitrile and chloride or two chloride ligands in the inner coordination sphere has been carried out. The steric and electronic effects of the substituents in the catalyst on the reaction yield has been studied.

Synthesis and Study of the Structure of Palladium(II) Acyclic Diaminocarbene Complexes Containing a 1,2,4-Oxadiazole Moiety

The reaction of anilines containing a 1,2,4-oxadiazole moiety with the bis(xylylisocyanide) Pd(II) complex leads to the formation of acyclic diaminocarbene complexes. The oxadiazole ring is not involved in the reaction. Composition and structure of the obtained complexes have been confirmed by means of mass spectrometry, NMR spectroscopy, and single-crystal X-ray diffraction analysis.

Synthesis of Bioactive N‐Acyclic Gold(I) and Gold(III) Diamino Carbenes with Different Ancillary Ligands

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.

Platinum(II)-mediated aminonitrone–isocyanide interplay: A new route to acyclic diaminocarbene complexes

The complex cis-[PtCl2(Me2SO)2] (1) reacts with 1equiv. of C-4-trifluoromethylphenyl-N-methylaminonitrone(2) to give the product [PtCl(Me2SO){ON(Me)C(4-CF3C6H4)NH}] (3; 75%). Treatment of 3 with an excess cyclohexyl isocyanide, CyNC, leads to the acyclic diaminocarbene complex [PtCl(CNCy){N(Me)C(4-CF3C6H4)NC(=NHCy)}] (4; 28%). The latter exhibits solid-state phosphorescence with an emission maximum at 600 nm and 23% quantum yield. Complexes 3 and 4 were characterized by HRESI+-MS, FTIR, 1H and 13C{1H} NMR spectroscopic techniques. The complex 4 was additionally characterized by X-ray diffraction; short PtPt contacts (3.2360(5)Å) were observed in the crystal structure. These non-covalent interactions have an attractive nature and their estimated strength is 4.6–5.6 kcal/mol.