Au‐NHC complexes with thiocarboxylate ligands: Synthesis, structure, stability, thiol exchange and in vitro anticancer activity

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Au-NHC complexes with thiocarboxylate ligands: Synthesis, structure, stability, thiol exchange and in vitro anticancer activity

N-Heterocyclic carbene complexes of gold bearing a thiocarboxylate ligand, (NHC)Au(SCOR), are stable and easily prepared. At elevated temperatures, they form equilibria with their disproportionation products [Au(NHC)2]+ and [Au(SCOR)2]−. (NHC)Au(SCOR) are active against a cisplatin-resistant ovarian cancer call line (OVCAR-8), exhibiting IC50 < 10 μM.


Novel complexes of form (NHC)Au(SCOR) (NHC = N-heterocyclic carbene, SCOR− = thiocarboxylate ligand) were synthesised and characterised by spectroscopic techniques and X-ray diffraction studies. The results of NMR and X-ray studies indicated that thiocarboxylate ligands are comparable with NHCs in their electron donor ability. The complexes were stable at room temperature in the solid state but in solution underwent disproportionation reactions to form equilibria with [Au(NHC)2]+ and [Au(SCOR)2]−. In solution, the thiocarboxylate ligand in (NHC)Au(SCOR) underwent rapid exchange with other thiocarboxylate or thiolate ligands. The (NHC)Au(SCOR) complexes showed toxicity against cisplatin-resistant ovarian cancer cells (OVCAR-8), with IC50 < 10 μM, in the range exhibited by cationic [Au(NHC)2]+ complexes well-known for their promising anticancer activity.

Synthesis and antiproliferative study of phosphorescent multimetallic Re(I)/Au(I) complexes containing fused imidazo[4,5‐f]‐1,10‐phenanthroline core

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Synthesis and antiproliferative study of phosphorescent multimetallic Re(I)/Au(I) complexes containing fused imidazo[4,5-f]-1,10-phenanthroline core

Heterometallic ReI/AuI complexes containing imidazo[4,5-f]-1,10-phenanthroline (N^N^C) as polytopic ligand were synthesised and their antiproliferative and emissive potential analysed. The gold complex bearing a thiolate sugar derivative is the most active complex.


Five heterobimetallic ReI/AuI and a tri-metallic ReI/AuI/ReI species following the formulas fac-[ReCl (CO)3(N^N^CAuR)]0/+ and [(fac-[ReCl (CO)3(N^N^C)])2Au]+, where R is an iodide (1), phenylacetylene (2), dodecanethiol (3), 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (4) and JohnPhos (5) and N^N^C is the fused imidazo[4,5-f]-1,10-phenanthroline heterotopic ligand, were synthesised and fully characterised by a variety of spectroscopic and analytical techniques. The resultant complexes are luminescent in the orange region, revealing classical metal-to-ligand charge transfer (3MLCT) ((Re (dπ) → (N^N^C)(π*)) emission in aerated DMSO solution. The red shifted emission observed on going from 3 to 4 suggests that the electronic properties of the gold ancillary ligand are implicated in the emissive properties. Antiproliferative activity in tumour cell lines, lung (A549) and cervix (HeLa) cells revealed that only complex 4 containing a 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose as gold ancillary ligand possesses certain cytotoxicity in both cell lines.

Direct dynamics simulation of the thermal O(3P) + dimethylamine reaction in the triplet surface. I. Rate constant and product branching

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Direct dynamics simulation of the thermal O(3P) + dimethylamine reaction in the triplet surface. I. Rate constant and product branching

Corresponding to the collision energy of 7.8 kcal/mol, the reaction between O(3P) and dimethylamine leads to two product channels, namely, (1) 2OH and 2CH3NHCH2 (major product) and (2) 2OH and 2CH3NCH3 (minor product). Both pathways follow direct and indirect H abstraction mechanisms.


Abstract

In order to provide atomistic details for the mechanism of the collisional dynamics of O(3P) and dimethylamine (DMA) in the triplet electronic surface, direct dynamics simulations are reported herein. The simulations are performed at the U-HSE06/aug-cc-pVDZ level of theory. The results are reported for the relative collision energy of 7.8 kcal/mol. For the vibrational and rotational excitations, following temperature regimes have been considered: 200 and 10 K, respectively. Simulations reveal that the reaction can lead to two product channels in the considered energy regime: (1) 2OH + 2CH3NHCH2 and (2) 2OH + 2CH3NCH3. The computed reaction cross section for pathways 1 and 2 are as follows: 17.89  ± 0.20 Å2 and 3.28  ± 0.03 Å2, whereas the computed microcanonical reaction rate constants for pathways 1 and 2 are as follows: (4.21  ± 0.05)*10−10 and (7.72  ± 0.07)*10−11 cm3/(molecule sec). Both pathways follow direct and indirect H abstraction processes. Among the direct pathways, stripping and rebound mechanisms have been observed, whereas the indirect pathway involves formation of a post-reaction complex having lifetime ~0.4–0.5 ps. The velocity scattering angle distribution for the reaction is dominated by scattering in the sideways (60–120 °) and backward (120–180 °) directions with some contribution from the scattering in the forward direction (0–60 °).