Acylthiourea Ligands Research Articles

Copper(I) complexes of acylthiourea ligands: structural insights and cytotoxic potential

The reaction of substituted acylthiourea derivatives (L1–L4) with [(PPh3)2Cu(μ‐Cl)2Cu(PPh3)] in a proper stoichiometric proportion gave the complexes (1–4) in good yields. The structures of the compounds (ligands and complexes) were advocated through spectroscopic analyses and x‐ray diffraction (XRD) studies; the latter confirmed their molecular structures. The complexes (1–4) were assessed for their cytotoxic potential through MTT assay against A549, T24, and HepG2 cancer cells, and their toxicity was evaluated using Vero and MCF‐10a normal cells. The complexes (1–4) displayed better cytotoxic action toward HepG2 cancer cells than cisplatin. Complexes 3 and 4 significantly destroyed A549 cancer cells with the IC50 values of 16.25 and 4.90 μM, respectively, which were lower than that of cisplatin (IC50 = 17.73 μM). Furthermore, the higher IC50 values in normal cells showed that the complexes were less hazardous to the normal cells except complex 3. The biocompatibility study showed that the complexes had minimal impact on normal human dermal fibroblast (NHDF) cells. The mode of cell death of complexes 3 and 4 against cancer cells was evaluated using staining assays. Both compounds demonstrated a significant reduction in live cells, an increase in early apoptotic cells, and pronounced proapoptotic effects, as evidenced by fragmented nuclei. Flow cytometry revealed a distinctive subpopulation in the subG0 phase, highlighting the compounds' ability to induce apoptosis and inhibit cell cycle progression.

Ru(II) and Ru(III) complexes containing N‐acylthiourea ligands: Supramolecular structures and synthons, reduction, and reaction pathway of aromatic nitro compounds

Four ruthenium complexes {[RuCl(CO)(PPh3)2L1], [RuCl(CO)(PPh3)2L2], [RuCl2(PPh3)2L1] and [RuCl2(PPh3)2L2]} supported with N‐acylthiourea‐based ligands were synthesized. The compounds prepared were characterized by 1H NMR, 13C NMR, elemental analysis, UV–vis, and magnetic susceptibility methods. The characterization of the molecular structure of two ruthenium complexes {[RuCl(CO)(PPh3)2L1] and [RuCl2(PPh3)2L1]} was also performed using the single crystal X‐ray diffraction method. Single crystal X‐ray analyses indicates the existence of different non‐covalent interactions between different parts of the molecules, which led to the formation of three‐dimensional supramolecular architectures and synthons. The magnetic susceptibility and UV‐vis spectra of the prepared ruthenium complexes propose that they are of low‐spin states, where Ru(II) is d6 and Ru(III) is d5 low spin. These ruthenium compounds functioned as catalysts for the NaBH4‐mediated reduction of various nitro compounds. The catalytic results show that the [RuCl2(PPh3)2L] type complexes exhibit higher catalytic activity than the [RuCl(CO)(PPh3)2L] type complexes, and [RuCl2(PPh3)2L1] has high catalytic selectivity and efficiency in a short time (>99 yield with catalyst loading 0.01 mol in 0.5 h). Furthermore, the catalytic activity of [RuCl2(PPh3)2L1] was investigated using nitrobenzene as a model substrate to understand the reaction pathway, and this study proved that this nitro reduction proceeds via a direct pathway, with the formation of N‐hydroxylamine as the main intermediate followed by the occurrence of aniline.

Cytotoxic and antiparasitic activities of diphosphine-metal complexes of group 10 containing acylthiourea as ligands

In this work, group 10 transition metal complexes bearing dppe [1,2-bis(diphenylphosphino)ethane] and acylthiourea ligands were evaluated for their cytotoxic and antiparasitic activities. Six new complexes with a general formula [M(Ln)(dppe)]BF4 [where M = NiII, PdII or PtII; Ln = N, N′-dimethyl-N-benzoyl thiourea (L1) or N, N′-dimethyl-N-tiofenyl thiourea (L2) were synthesized and characterized by infrared, NMR (31P{1H}, 1H and 13C{1H}) spectroscopies, elemental analysis and molar conductivity. The structures of the complexes were confirmed by X-ray diffraction technique. The biological activity of the complexes was evaluated on breast cancer cells (MDA-MB-231 and MCF-7) and causative agents of chagas disease and leishmaniasis. The complexes presented higher cytotoxicity for breast cancer cell lines compared to non-tumor cells. Nickel complexes stood out when evaluated against the triple-negative breast cancer line (MDA-MB-231), presenting considerably lower IC50 values (about 10 to 22×), when compared to palladium and platinum complexes, and the cisplatin drug. When evaluated on the triple-negative line (MDA-MB-231), the complexes [Ni(L2)(dppe)]BF4(2), [Pd(L2)(dppe)]BF4(4) and [Pt(L2)(dppe)]BF4(6) were able to induce cell morphological changes, influence on the cell colony formation and the size of the cells. The complexes inhibit cell migration and cause changes to the cell cytoskeleton and nuclear arrangement. In the same cell line, the compounds caused cell arrest in the Sub-G1 phase of the cell cycle. The compounds were also tested against the Trypanosom Cruzi (T. cruzi) and Leishmania sp. parasites, which cause Chagas and leishmaniasis disease, respectively. The compounds showed good anti-parasitic activity, mainly for T. cruzi, with lower IC50 values, when compared to the commercial drug, benznidazole. The compounds interact with CT-DNA, indicating that interaction occurs by the minor groove of the biomolecule.

Pd(II)–PPh3 complexes of halogen substituted acylthiourea ligands: Biomolecular interactions and in vitro anti‐proliferative activity

AbstractHerein, we report the synthesis of four new Pd(II) acylthiourea complexes (C1–C4) to study the effect of halogen substituted acylthiourea ligands on the biological applications of their Pd(II)–PPh3 complexes. The complexes were characterized by various spectroscopic and analytical methods. The distorted square planar geometry of complexes was confirmed by single crystal X‐ray diffraction study, which also revealed the bidentate (N, S) coordination of the ligands with Pd(II). Interactions of the complexes with biomolecules (DNA/BSA) were investigated by spectroscopic and docking tools. All the complexes showed good binding ability with the targeted biomolecules. Further, in vitro anti‐proliferative activity of the complexes was investigated by performing MTT assay on cancer (HeLa‐cervical, HCT116‐colorectal, and HepG2‐hepatic) and normal (HEK293‐embryonic kidney) cell lines. All the complexes displayed remarkable activity on the three cancer cells, and among them, complex C2 bearing chlorine substituted acylthiourea showed superior activity on HeLa cells with an IC50 value of 6.5 μM, which was higher than that of cisplatin. Apoptosis induced by C2 on HeLa cells was assessed by AO/EB, DAPI and DNA laddering assays, and flow cytometry. Finally, the apoptotic efficiency of C2 was tested by cell cycle analysis, wherein the complex induced the cell cycle arrest in HeLa cells at G0/G1 phase.

Bidentate acylthiourea ligand anchored Pd-PPh3 complexes with biomolecular binding, cytotoxic, antioxidant and antihemolytic properties

Acylthiourea-based Pd(II) complexes (1–5) with a PPh3 moiety bearing the general formula [PdCl(PPh3)(L-R)] [L-R = monoanionic bidentate acylthiourea ligand, where R = C6H5 (L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7 (L4) or C6H4Cl (L5)] have been synthesized and characterized by spectroscopic and analytical tools. The single crystal X-ray structures (1–3) revealed that the acylthiourea ligands coordinated to Pd(II) ion in an uncommon bidentate fashion through S and N atoms, forming a four-member ring. The Pd(II) ion exhibited a square planar geometry fulfilled by the ligand (N, S), one Cl‐ and one triphenylphosphine (PPh3). Calf thymus (CT) DNA and bovine serum albumin (BSA) binding of the complexes have been analyzed by spectroscopic and molecular docking studies. The complexes were tested for their in vitro cytotoxicity on three cancer (cervical, breast and lung) and one normal (human embryo) cell lines. Complex 4 bearing the naphthalene substitution exhibited the highest activity against three cancer cells with the half-maximal inhibitory concentration (IC50) values of 8.6 (cervical), 8.8 (breast) and 9.4 μM (lung). The acridine orange/ethidium bromide (AO/EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining assays indicated that 4 induced cancer cell death through apoptosis. Among the complexes, 4 exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of 86.19%. All the complexes were subjected to the hemolysis assay which revealed their biocompatibility with red blood cells (RBCs) with a lysis rate of less than 5 %.

Ruthenium(II)-diphosphine complexes containing acylthiourea ligands are effective against lung and breast cancers.

We have synthesized and characterized three new ruthenium(II) diphosphine complexes containing an acylthiourea ligand, with the general formula [Ru(DPEPhos)(O,S)(bipy)]PF6, where DPEPhos = bis(2-(diphenylphosphino)phenyl)ether, bipy = 2,2'-bipyridine, and O,S = N,N-dimethyl-N'-(benzoyl)thiourea (1), N,N-dimethyl-N'-(furoyl)thiourea (2), and N,N-dimethyl-N'-(thiophenyl)thiourea (3), by several physicochemical techniques. We evaluated the ruthenium complexes for their cytotoxicity against two human cancer cell lines, A549 (lung) and MDA-MB-231 (breast), and two corresponding lines of non-cancer cells, MRC-5 (lung) and MCF-10A (breast). All the complexes are cytotoxic against the cancer cell lines; the IC50 values lie in the micromolar range (0.07-0.70 μM). Ruthenium complex 1 is more selective (7 times more active) toward lung cancer cells (A549) than toward non-cancer cells (MRC-5) and is 160 times more cytotoxic than cisplatin against A549 cells. Investigations of the mechanism of action of complex 1 in A549 cells demonstrated that it inhibits colony formation and promotes cell cycle arrest in the G1 phase and apoptotic cell death. DNA binding studies revealed that complexes 1-3 interact with the biomolecule via minor grooves. These complexes also interact with human serum albumin (HSA) and have affinity for site I by hydrophobic forces. Therefore, this new class of ruthenium complexes can act as cytotoxic agents, mainly for lung cancer treatment.

Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N'-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells.

Six complexes with the general formula [Cu(acylthioureato)(PPh3)2] were synthesized and characterized using spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), mass spectrometry, elemental analysis, and X-ray diffraction. Interpretation of the in vitro cytotoxicity data of Cu(I) complexes took into account their stability in cell culture medium. DFT calculations showed that NMR properties, such as the shielding of carbon atoms, are affected by relativistic effects, supported by the ZORA Hamiltonian in the theoretical calculations. Additionally, the calculation of the energies of the frontier molecular orbitals predicted that the structural changes of the acylthiourea ligands did not cause marked changes in the reactivity descriptors. All complexes were cytotoxic to the evaluated tumor cell lines [MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast cancer), and A549 (lung cancer)]. In the MDA-MB-231 cell line, complex 1 significantly altered the cytoskeleton of the cells, reducing the density and promoting the condensation of F-actin filaments. In addition, the compound caused an increase in the percentage of cells in the fragmented DNA region (sub-G0) and induced cell death via the apoptotic pathway starting at the IC50 concentration. Taken together, the results show that complex 1 has cytotoxic and apoptotic effects on TNBC cells, which is a cell line originating from an aggressive, difficult-to-treat breast cancer.

Ruthenium(II) complexes bearing bidentate acylthiourea ligands for direct oxidation of amine α-carbon to amide

In this study, the synthesis and structural characterization of ruthenium complexes supported by S,O-acylthiourea ligands (L1-L6) with different substituent groups as well as auxiliary ligands PPH3, CO, and Cl and their evaluation as catalysts for direct oxidation of the α-methylene group in amines were reported. Ru(II) complexes, Ru1-Ru6, were prepared from the reaction of the RuH(CO)Cl(PPh3)3 precursor and ligands L1-L6 having different electronic and steric properties. The ligands and complexes prepared were characterized by FT-IR, 1H–13C- and/or 31P NMR spectroscopic techniques. The molecular structures of Ru1 and Ru3 complexes with appropriate crystal quality were also confirmed by X-ray single crystal analysis. Solid-state structures of Ru1 and Ru3 revealed that the ruthenium center is surrounded by one carbonyl, one chloride, two PPh3 ligands, and the S,O-donor atoms from the acylthiourea ligand in bidentate monoanionic form. The catalytic activity of all complexes for the α-oxygenation reactions of primary benzylic amines to amides was investigated. Overall, all catalysts exhibited excellent activity and selectivity towards the formation of amide production under the present reaction conditions. In addition, both catalyst activation and product selectivity/formation were particularly dependent on the amount/type of base and oxygen.

Impact of aliphatic acyl and aromatic thioamide substituents on the anticancer activity of Ru(II)-p-cymene complexes with acylthiourea ligands-in vitro and in vivo studies.

Six different acylthiourea ligands (L1-L6) and their corresponding Ru(II)-p-cymene complexes (P1-P6) were designed to explore the structure-activity relationship of the complexes upon aliphatic chain and aromatic conjugation on the C- and N-terminals, respectively. The compounds were synthesized and adequately characterized using various analytical and spectroscopic techniques. The structures of P2-P6, solved using single crystal X-ray diffraction (XRD), confirmed the neutral monodentate coordination of the S atoms of the acylthiourea ligands to Ru(II) ions. In silico studies showed an increase of lipophilicity for the ligands with an increase in alkyl chain length or aromatic conjugation at the C- or N-terminal, respectively. Subsequently, mitogen-activated protein kinases (MAPK) were predicted as one of the primary targets for the complexes, which showed good binding affinity towards extracellular signal-regulated kinases (ERK1, ERK2 and ERK5), c-Jun N-terminal kinase (JNK) and p38 of the MAPK pathway. Henceforth, the complexes were tested for their anticancer activity in lung carcinoma (A549) and cisplatin-resistant lung carcinoma (cisA549R) cells and human umbilical vein epithelial normal cells (HUVEC). Interestingly, an increase in chain length or aromatic conjugation led to an increase in the activity of the complexes, with P5 (7.73 and 13.04 μM) and P6 (6.52 and 14.45 μM) showing the highest activity in A549 and cisA549R cells, which is better than the positive control, cisplatin (8.72 and 44.28 μM). Remarkably, we report the highest activity yet observed for complexes of the type [(η6-p-cymene)RuIICl2(S-acylthiourea)] in the tested cell lines. Aqueous solution studies showed that complexes P5 and P6 are rapidly hydrolyzed to produce solely aquated species that remained stable for 24 h. Staining assays and flow cytometric analyses of P5 and P6 in A549 cells revealed that the complexes induced apoptosis and arrested the cell cycle predominantly in the S phase. In vivo studies demonstrated the higher toxicity of cisplatin and a comparatively higher survival rate of mice injected with the most active complex P6. Histological analyses revealed that treatment with P6 at high doses of up to 8 mg kg-1 did not cause any palpable damage to the tested organs.

Antitumor activity of Pd(II) complexes with N,S or O,S coordination modes of acylthiourea ligands

Seven new complexes (1–7) of Pd(II) with N-alkyl- and N,N-dialkyl-N′-acylthioureas were prepared and characterized by elemental analysis and spectroscopic techniques. The crystal structures of the coordination compounds [PdCl(PPh3)(5-cloropiridyl-N′-benzoylthioureato-k2N,S)] (2), cis-[Pd(PPh3)2(N-morpholyn-N′-benzoylthioureato-k2O,S)]PF6 (4) and cis-[Pd(PPh3)2(N,N-diphenyl-N′-thiophenylthioureato-k2O,S)]PF6 (7) were determined by X-ray crystallography. The present study reports on an interesting contribution on the chemistry of Pd(II)/acylthiourea complexes, where the use of monosubstituted acylthiourea conducts to formation of neutral complexes with general formula [Pd(Cl)(PPh3)(acylthiourea)], with a N,S-coordination mode. On the other hand, cationic complexes with formula [Pd(PPh3)2(acylthiourea)]+, with O,S bidentately coordinated to the metal, are obtained by using a disubstituted acylthiourea derivative. The antitumor activity of the N-alkyl- and N,N-dialkyl-N′-acylthiourea ligands and their palladium (II) complexes with synthesized triphenylphosphine were evaluated against the growth of the DU-145 tumor cells (prostate cancer cells), (MDA-MB-231 (breast cancer cells), L929 (healthy mouse cells). The ligands are not cytotoxic, but the complexes showed good cytotoxicity against the tumor cells tested in this work, and were even better, when compared to the IC50 reported for the cisplatin. The complexes showed better activity results in MDA-MB-231 tumor cells, than for the DU-145 tumor cells. Complexes 1 and 6 showed high cytotoxic activity at low micromolar concentrations (IC50 = 1.93 ± 0.45, 0.62 ± 0.08 μM) against MDA-MB-231 (human breast cancer cells). This result indicated that the binding of the ligands to the metal center increases their antitumor activity.

New E,Z platinum(II) complexes of asymmetrically di-substituted-acyl(aroyl)thioureas: Synthesis, characterization, photo-induced isomerism

A series of cis-[Pt(L-κS,O)2] complexes derived from the asymmetrically substituted N,N-dialkyl-N’-acyl(aroyl)thiourea ligands HL1-5 have been synthesized and characterized by 1H, 13C, HMBC and 1D NOESY NMR spectroscopy. The complexes exist in chloroform as cis-ZZ-[Pt(L-κS,O)2], cis-EE-[Pt(L-κS,O)2] and cis-ZE-[Pt(L-κS,O)2] configurational isomers revealing three well-resolved 195Pt{1H} resonances in the chemical shift range δ = −2710 to −2718 ppm. The results show that the presence of long chain N-alkyl or bulky N-phenyl groups favored a higher relative distribution of the cis-ZZ-[Pt(L-κS,O)2] isomer compared to complexes with smaller N-alkyl substituents. Single-crystal X-ray diffraction studies show that in chloroform, a cis-EE-[Pt(L1-κS,O)2] isomer is isolated when N-ethyl,N-methyl groups are attached to the thioamidic moiety, whereas cis-[Pt(L5-κS,O)2] having N-phenyl,N-isopropyl groups crystallized as a cis-ZZ isomer. Irradiation of a mixture of cis-ZZ/EZ/EE-[Pt(L-κS,O)2] configurational isomers in chloroform-d showed the formation of three additional 195Pt{1H} resonances ascribed to trans-ZZ/ZE/EE-[Pt(L-κS,O)2] geometric isomers in the range δ = −1950 to −2000 ppm.

Selective Coordination Mode of Acylthiourea Ligands in Half-Sandwich Ru(II) Complexes and Their Cytotoxic Evaluation.

In this study, half-sandwich Ru(II) complexes containing acylthiourea ligands of the general type [Ru(η6-p-cymene)(PPh3)(S)Cl]PF6 (1m-6m) and [Ru(η6-p-cymene)(PPh3)(S-O)]PF6 (1b-6b) where S/S-O = N',N'-disubstituted acylthiourea were synthesized and characterized (via elemental analyses, IR spectroscopy, 1H NMR spectroscopy, 13C{1H} NMR spectroscopy, and X-ray diffractometry), and their cytotoxic activity was evaluated. The different coordination modes of the acylthiourea ligands, monodentately via S (1m-6m) and bidentately via S,O (1b-6b), to ruthenium were modulated from different synthetic routes. The cytotoxicity of the complexes was evaluated in five human cell lines (DU-145, A549, MDA-MB-231, MRC-5, and MCF-10A) by MTT assay. The IC50 values for prostate cancer cells (2.89-7.47 μM) indicated that the complexes inhibited cell growth, but that they were less cytotoxic than cisplatin (2.00 μM). Unlike for breast cancer cells (IC50 = 0.28-0.74 μM) and lung cancer cells (IC50 = 0.51-1.83 μM), the complexes were notably more active than the reference drug, and a remarkable selectivity index (SI 4.66-19.34) was observed for breast cancer cells. Based on both the activity and selectivity, complexes 5b and 6b, as well as their respective analogous complexes in the monodentate coordination 5m and 6m, were chosen for further investigation in the MDA-MB-231 cell line. These complexes not only induced morphology changes but also were able to inhibit colony formation and migration. In addition, the complexes promoted cell cycle arrest at the sub-G1 phase inducing apoptosis. Interaction studies by viscosity measurements, gel electrophoresis, and fluorescence spectroscopy indicated that the complexes interact with the DNA minor groove and exhibit an HSA binding affinity.

Tuning acylthiourea ligands in Ru(II) catalysts for altering the reactivity and chemoselectivity of transfer hydrogenation reactions, and synthesis of 3-isopropoxy-1H-indole through a new synthetic approach

Ru(II)-p-cymene complexes (1–3) containing picolyl based pseudo-acylthiourea ligands (L1-L3) were synthesized and characterized. The crystallographic study confirmed the molecular structures of all the ligands (L1-L3) and complex 3. The catalytic activity of the complexes was tested mainly towards TH of carbonyl compounds and nitroarenes. The influence of steric and electronic effects of the ligands on the chemoselectivity and reactivity were reported. The catalytic activity was enhanced and chemoselectivity was switched after tuning the ligands in the catalysts, compared to their corresponding unmodified Ru(II)-p-cymene complexes. The catalysis was extended to a broad range of substrates including some challenging systems like furfural, benzoylpyridine, benzoquinone, chromanone, etc. The strategy of tuning the bifunctional ligands in the catalysts for effective and selective catalysis worked nicely. Further, the catalysis was extended to one pot synthesis of 3-isopropoxyindole from 2-nitrocinnamaldehyde, the first synthetic route similar to Baeyer Emmerling indole synthesis. All the catalytic experiments exhibited high conversion and selectivity.

Hirshfeld surface analysis of some new heteroleptic Copper(I) complexes

Seven new coordination complexes namely, [Cu(T1) (I) (PPh3)2] (CT1), [Cu(T2) (I) (PPh3)2] (CT2), [Cu(T3) (I) (PPh3)2] (CT3), [Cu(T4) (I) (PPh3)2] (CT4), [Cu(T5) (I) (PPh3)2] (CT5), [Cu(T6) (I) (PPh3)2] (CT6) and [Cu(T7) (I) (PPh3)2] (CT7), were synthesized and characterized by using spectroscopic and crystallographic methods. The results from spectroscopic data and crystal structure analysis showed that in all complexes, the acylthiourea ligands coordinated as monodentate S-donor mode. All of the complexes displayed distorted tetrahedral geometry with one iodide anion, two triphenylphosphine ligands and one acylthiourea ligand (N-benzoyl-N′-(substituted phenyl)thiourea bearing different ortho/meta-substituents; R–H, 3-Me, 3-OMe, 3-OH, 3-Cl, 2-Me and 2-OMe, T1-T7 respectively) attached to the Cu(I) central metal atom. The acylthiourea ligands behaved as a monodentate S-donor ligand instead of its common O, S-bidentate nature due to the tetrahedrally favored geometry of the copper(I) metal and the presence of two bulky group of triphenylphosphine ligand as the co-ligand. Interestingly, CT1-CT4 and CT7 crystals are isostructural and crystallized in the monoclinic P21/c crystal system whereas CT5 and CT6 are also isostructurally crystallized in the triclinic P1¯ crystal system. Isostructural structures of these two crystal systems illustrated almost similar crystal packing but with significantly different interactions as determined by Hirshfeld surface analysis which is discussed herein.

Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes using acylthiourea based Ru(II)(p-cymene) complexes as precatalysts

A new series of Ru(II)(η6-p-cymene) complexes (1–5) was synthesized from pyridine based acylthiourea ligands (L1-L5) and [Ru(η6-p-cymene)Cl2]2. All the ligands and complexes were well characterized by UV-Visible, FT-IR, mass and 1H &13C NMR spectroscopic techniques. The molecular structures of the ligands (L1, L2, L4, and L5) and complex 1 were confirmed using single crystal X-ray diffraction study. The Ru(II)(η6-p-cymene) complexes (1–5) were proved to be efficient precatalysts for the transfer hydrogenation of carbonyl compounds and nitroarenes in the presence of 2-propanol as a hydrogen donor and KOH as a base. The catalytic transfer hydrogenation reactions were chemoselective towards the nitro group in presence of carbonyl group, which is a rare scenario in homogeneous catalysis. The catalyst was compatible with broad range of substrates which include furfural, quinone and many heterocycles. The catalytic reactions exhibited very high conversions (upto 100%) and excellent yields (upto 99%). Turn Over Number (TON) was found upto 990.

Hydrolysis reaction promotes changes in coordination mode of Ru(II)/acylthiourea organometallic complexes with cytotoxicity against human lung tumor cell lines

In this study, Ru(II)-arene complexes with acylthiourea ligands of the type [Ru(η6‑p‑cymene)(PPh3)(T)Cl]PF6(1–5) and [Ru(η6‑p‑cymene)(PPh3)(T)]PF6(1a, 4a), where PPh3 = triphenylphosphine and T = N‑acyl‑N′(monosubstituted)thiourea, were synthesized and characterized, and their cytotoxic properties were also evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4. All complexes showed unusual coordination modes for acylthiourea ligands, which are coordinated in a monodentate fashion (S) in 1–5, while they found to be bidentate (S,N), in 1a and 4a. To the best of our knowledge, 1a and 4a are the first crystallographically reported ruthenium compounds with acylthiourea coordinated via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in human lung cells, A549 and MRC-5. The IC50 values ranging from 0.25 to 0.61 μM after 48 h incubation in lung cancer cells indicate that the compounds showed high cytotoxicity with values significantly lower than the reference drug, cisplatin (11.84 μM). Interaction studies were carried out using human serum albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however complex 1a, which is the hydrolysis product of 1, presented the highest activity and selectivity among all seven compounds synthesized here. Complexes 1 and 1a inhibited the colony formation decreasing the colony size and inducing morphology changes in A549 cells. These complexes induced apoptosis cell death and promoted cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S phase.

The trans-[Ru(PPh3)2(N,N-dimethyl-N′-thiophenylthioureato-k2O,S)(bipy)]PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-[Ru(PPh3)2(N,N-dibutyl-N′-benzoylthioureato-k2O,S)(2,2′-bipyridine (bipy))]PF6(1), trans-[Ru(PPh3)2(N,N-dimethyl-N′-thiophenylthioureato-k2O,S)(bipy)]PF6(2) and trans-[Ru(PPh3)2(N,N-dimethyl-N′-benzoylthioureato-k2O,S)(bipy)]PF6(3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice.

N,N-Disubstituted-N'-acylthioureas as modular ligands for deposition of transition metal sulfides.

First row transition metal complexes (Ni, Co, Cu, Zn) with N,N-disubstituted-N'-acylthiourea ligands have been synthesized and characterized. Bis(N,N-diisopropyl-N'-cinnamoylthiourea)nickel was found to have the lowest onset temperature for thermal decomposition. Thin film deposition of Ni, Co, and Zn sulfides by aerosol assisted chemical vapor deposition from their respective N,N-diisopropyl-N'-cinnamoylthiourea complexes at 350 °C has been demonstrated.

Synthesis and Characterization of Copper Complexes with the N‐(2,6‐Diisopropylphenyl)‐N′‐acylthiourea Ligands

Three N‐(2,6‐diisopropylphenyl)‐N′‐acylthiourea ligands [Ar′NHC(S)NHC(O)Ar; Ar′ = 2,6‐iPr2C6H3; Ar = p‐tBuC6H4 (1, L1), Mes (2, L2), and 1‐Naph (3, L3)] were synthesized and compared with the homologous ligand L0 (Ar = Ph) in terms of their resultant complexes with copper halides. The reaction of L1 with CuCl2 led to the formation of mononuclear L12CuCl (4), while treatment of L1 with CuX (X = Cl, Br) resulted in the adamantane cage complexes (L1CuX)4 (X = Cl, 5; Br, 6). These findings are similar to the results shown by its parent ligand L0. The reaction of L1 with CuI yielded the iodide‐bridged dimeric complex [L12Cu(µ‐I)]2 (7), in contrast to the ligand‐bridged dimer supported by L0. L2 readily afforded the mononuclear CuI complexes 8–10 coordinated by two or three ligands. L3 gave monomeric L33CuX (X = Cl, 11; Br, 12) and the iodide‐bridged dimeric [L32Cu(µ‐I)]2 (13). L3 can bind with CuI halides in a ratio of 1:1 to give complexes L3CuX(PPh3)2 (14–16), when Cu2X2(PPh3)3 (X = Cl, Br) or CuI(PPh3)3 were used as precursors. Treatment of (L1CuCl)4 (5), L22CuBr (8), and L33CuCl (11), respectively, with hot EtOH resulted in the formation of trans‐CuLn′2 (17–19) compounds. All compounds were characterized by single‐crystal X‐ray diffraction studies.

Synthesis, characterization and catalytic oxidation property of copper(I) complexes containing monodentate acylthiourea ligands and triphenylphosphine

The reactions between [CuCl2(PPh3)2] and 3,3-diphenyl-1-(2,4-dichlorobenzoyl)thiourea (HL1), 3,3-diisobutyl-1-(2,4-dichlorobenzoyl)thiourea (HL2) or 3,3-diethyl-1-(2,4-dichlorobenzoyl)thiourea (HL3) in benzene gave new four-coordinated tetrahedral copper(I) complexes of the type [CuCl(HL)(PPh3)2] (1–3) [HL=3,3-dialkyl/aryl-1-(2,4-dichlorobenzoyl)thiourea derivatives]. These complexes were then characterized by analytical and spectroscopic (IR, UV/Vis, 1H, 13C and 31P NMR) techniques. The molecular structure of a representative complex, [CuCl(HL1)(PPh3)2] (1), was determined by the single crystal X-ray diffraction method which reveals a distorted tetrahedral geometry around the Cu(I) ion. The complexes 1–3 (0.007mmol) were found to be active catalysts for the oxidation of primary and secondary alcohols 5.0mmol to their corresponding acids and ketones, respectively, in the presence of hydrogen peroxide (6.0mmol) in 1-butyl-3-methylimidazolium hexafluorophosphate {[bmim][PF6]} (0.1mL) without any additive and base, at 70°C.