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.

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.

Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural Characterization, and Cytotoxicity Studies.

Well-defined diazotates are scarce. Here we report the synthesis of unprecedented homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated nitrosylation of 2-aminopyridines with NaNO2 results in the formation of metal-stabilized diazotates, which were found to be cytotoxic to human ovarian cancer cells.

Identification and H(D)-bond energies of C-H(D)Cl interactions in chloride-haloalkane clusters: a combined X-ray crystallographic, spectroscopic, and theoretical study.

The cationic (1,3,5-triazapentadiene)Pt(II) complex [Pt{NH[double bond, length as m-dash]C(N(CH2)5)N(Ph)C(NH2)[double bond, length as m-dash]NPh}2]Cl2 ([]Cl2) was crystallized from four haloalkane solvents giving [][Cl2(CDCl3)4], [][Cl2(CHBr3)4], [][Cl2(CH2Cl2)2], and [][Cl2(C2H4Cl2)2] solvates that were studied by X-ray diffraction. In the crystal structures of [][Cl2(CDCl3)4] and [][Cl2(CHBr3)4], the Cl(-) ion interacts with two haloform molecules via C-DCl(-) and C-HCl(-) contacts, thus forming the negatively charged isostructural clusters [Cl(CDCl3)2](-) and [Cl(CHBr3)2](-). In the structures of [][Cl2(CH2Cl2)2] and [][Cl2(C2H4Cl2)2], cations [](2+) are linked to a 3D-network by a system of H-bondings including one formed by each Cl(-) ion with CH2Cl2 or C2H4Cl2 molecules. The lengths and energies of these H-bonds in the chloride-haloalkane clusters were analyzed by DFT calculations (M06 functional) including AIM analysis. The crystal packing noticeably affected the geometry of the clusters, and energy of C-HCl(-) hydrogen bonds ranged from 1 to 6 kcal mol(-1). An exponential correlation (R(2) > 0.98) between the calculated Cl(-)H distances and the energies of the corresponding contacts was found and used to calculate hydrogen bond energies from the experimental Cl(-)H distances. Predicted energy values (3.3-3.9 kcal mol(-1) for the [Cl(CHCl3)2](-) cluster) are in a reasonable agreement with the energy of the Cl3C-HCl(-) bond estimated using ATRFTIR spectroscopy (2.7 kcal mol(-1)).

Coupling of platinated triguanides with platinum-activated nitriles as a novel strategy for generation of dimetallic systems.

One of two Pt(IV)-activated propanenitriles in trans-[PtCl4(EtCN)2] is involved in platinum(IV)-mediated nitrile-imine coupling with the platinum(II)-based metallacycles [PtCl2{NH=C(NR2)N(Ph)C(=NH)N(Ph)C(NR2)=NH}] [R2 = Me2 (1a), C5H10 (1b)] yielding diplatinum products, whose structures depend on molar ratios between the reactants. At a 1 : 1 ratio, the mixed-valence platinum(II)/platinum(IV) species [PtCl4{NH=C(NR2)N(Ph)C{=[(N(Et)C=NH)PtCl2(EtCN)]}N(Ph)C(NR2)=NH}] [R2 = Me2 (2a), (CH2)5 (2b)] were generated, whereas at a 1 : 2 ratio the dinuclear platinum(II)/platinum(II) complexes [PtCl2{NH=C(NR2)N(Ph)C{=[(N(Et)C=NH)PtCl2(EtCN)]}N(Ph)C(NR2)=NH}] [R2 = Me2 (3a), (CH2)5 (3b)] were obtained. In contrast to the nitrile-imine coupling observed for the platinum(IV) dinitrile complex, the reaction between the platinum(II) congener trans-[PtCl2(EtCN)2] and any one of 1a,b gives exclusively the substituted dimetallic platinum(II)/platinum(II) products [PtCl2{NH=C(NR2)N(Ph)C{=[(NH)PtCl2(EtCN)]}N(Ph)C(NR2)=NH}] [R2 = Me2 (6a), (CH2)5 (6b)] featuring platinum-containing guanidine 1 as one of the ligands. Complexes 2a,b, 3a,b, and 6a,b were characterized by elemental analyses (C, H, N), HRESI-MS, IR, (1)H NMR spectroscopy, and DTA/TG. The molecular and crystal structure of 2a·2CDCl3 was additionally studied by single-crystal X-ray diffraction. Complexes 2a,b undergo further redox transformation in solutions, and single crystals of [PtCl2{NH=C(NMe2)N(Ph)C{=[(N(Et)C=NH)PtCl2(MeCN)]}N(Ph)C(NMe2)=NH}]·2CH2Cl2 (3'a·2CH2Cl2) were obtained from 2a in a CH2Cl2-MeCN-C2H4Cl2 mixture and studied by X-ray crystallography. The driving forces for the generation of diplatinum products 2 and 3 were elucidated based on a quantum-chemical study.

Gold(I) thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents.

Gold(i) complexes with phosphane and thiotetrazolate ligands were prepared and investigated as a new type of bioactive gold metallodrugs. The complexes triggered very efficient inhibition of the enzyme thioredoxin reductase (TrxR), which is an important molecular target for gold species. Strong cytotoxic effects were observed in MDA-MB-231 breast adenocarcinoma and HT-29 colon carcinoma cells, and the complexes also caused strong effects in vincristine resistant Nalm-6 leukemia cells. Cellular uptake studies showed elevated cellular gold levels for complexes containing a triphenylphosphane ligand, whereas trifurylphosphane analogues accumulated at significantly lower cellular concentrations.

Synthesis, characterization, and biological evaluation of new tetrazole-based platinum(II) and palladium(II) chlorido complexes--potent cisplatin analogues and their trans isomers.

Two series of tetrazole-containing platinum(II) and palladium(II) chlorido complexes, trans-[ML(2)Cl(2)] (M=Pt, Pd) and cis-[PtL(2)Cl(2)]·nH(2)O (n=0, 1), where L is 1- or 2-substituted 5-aminotetrazole, have been synthesized and thoroughly characterized. Configuration of platinum(II) complexes obtained from the reaction of 5-aminotetrazoles with K(2)PtCl(4) has been found to vary depending on the nature of tetrazole derivatives and reaction conditions. According to in vitro cytotoxic evaluation, only platinum complexes display noticeable antiproliferative effect, and their cytotoxicity depends strongly on their geometry and hydrophobicity of the carrier ligands. The most promising complexes are cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O, where 1-apt is 5-amino-1-phenyltetrazole and 2-abt is 5-amino-2-tert-butyltetrazole. In comparison with cisplatin, they show comparable cytotoxic potency against cisplatin-sensitive human cancer cell lines, cis-[Pt(2-abt)(2)Cl(2)]·H(2)O performing substantially higher activity against cisplatin-resistant cell lines. Cell cycle studies in H1299 cell line indicated that cis-[Pt(2-abt)(2)Cl(2)]·H(2)O induced apoptosis launched from G2 accumulations. The DNA interaction with cis-[Pt(1-apt)(2)Cl(2)]·H(2)O was followed by UV spectroscopy, circular dichroism, hydrodynamic and electrophoretic mobility studies. Both cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O complexes appeared to be significantly less toxic than cisplatin in mice, while only compound cis-[Pt(1-apt)(2)Cl(2)]·H(2)O displayed noticeable efficacy in vivo.

catena-Poly[[bis-[1-(2-hydroxy-ethyl)-1H-tetra-zole-κN]copper(II)]-di-µ-chlorido]: a powder study.

The crystal structure of the title polymeric complex, [CuCl(2)(C(3)H(6)N(4)O)(2)](n), was obtained by the Rietveld refinement from laboratory X-ray powder diffraction data collected at room temperature. The unique Cu(II) ion lies on an inversion center and is in a slightly distorted octa-hedral coordination environment. In the hydroxy-ethyl group, all H atoms, the O atom and its attached C atom are disordered over two positions; the site occupancy factors are ca 0.6 and 0.4. The OH group is involved in an intra-molecular O-H⋯N hydrogen bond.

Bis(1-methyl-1H-tetrazol-5-yl)diazene and two its copper(I) chloride complexes poly[[[mu-1,2-bis(1-methyl-1H-tetrazol-5-yl)diazene-kappa4N',N4:N,N4']dicopper(I)]-di-mu-chloro] and catena-poly[[chlorocopper(I)]-mu-1,2-bis(1-methyl-1H-tetrazol-5-yl)diazene-kappa4N',N4:N,N4'].

While bis(1-methyl-1H-tetrazol-5-yl)diazene, C4H6N10, (I), has no crystallographically imposed symmetry, in the two title chlorocopper(I) complexes, [Cu2Cl2(C4H6N10)]n, (II), and [CuCl(C4H6N10)]n, (III), the organic ligands lie across centres of inversion; in (III), the Cu and Cl atoms additionally lie about a twofold rotation axis in the space group P2/c. Complex (II) forms a two-dimensional coordination polymer containing tetrahedrally coordinated Cu(I) atoms, and complex (III) forms a one-dimensional coordination polymer containing five-coordinate square-pyramidal Cu(I) atoms.