A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas

Tetrahedral copper(I) TpCuP complexes 1-15, where Tp is a N,N,N-tris(azolyl)borate and P is a tertiary phosphine, have been synthesized and characterized by means of NMR, ESI-MS, and XAS-EXAFS, and X-ray diffraction analyses on the representative complexes 1 and 10, respectively. All copper(I) complexes were evaluated for their antiproliferative activity against a panel of human cancer cell lines (including cisplatin and multidrug-resistant sublines). The two most effective complexes [HB(pz)3]Cu(PCN), 1, and [HB(pz)3]Cu(PTA), 2, showed selectivity toward tumor vs normal cells, inhibition of 26S proteasome activity associated with endoplasmic reticulum (ER) stress, and unfolded protein response (UPR) activation. No biochemical hallmarks of apoptosis were detected, and morphology studies revealed an extensive cytoplasmic vacuolization coherently with a paraptosis-like cell death mechanism. Finally, the antitumor efficacy of complex 1 was validated in the murine Lewis Lung Carcinoma (LLC) model.

In vitro and in vivo anticancer activity of copper(I) complexes with homoscorpionate tridentate tris(pyrazolyl)borate and auxiliary monodentate phosphine ligands.

A luminescent hydrogel based on a new Au(I) complex

Homoleptic, tetrahedral Cu(i) complexes of the type [Cu(P)4]BF4 (1-3), where P are the phosphine ligands, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) and 2-thia-1,3,5-triaza-phosphoaadamantane-2,2-dioxide (PTA-SO2), have been prepared. Novel complexes [Cu(DAPTA)4]BF42 and [Cu(PTA-SO2)4]BF43 have been fully characterized by means of spectroscopic methods, corroborated by XAS-EXAFS analysis of 2. In vitro cell culture experiments revealed a significant antiproliferative activity for Cu(i) compounds against several human cancer cell lines derived from solid tumors with preferential cell growth inhibition towards tumour compared to non-malignant cells. In vitro monitoring of migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) showed an anti-angiogenic effect of copper(i) complexes at sub-cytotoxic concentrations. In vivo studies on the antitumor efficacy and ability to inhibit angiogenesis confirmed the dual cytotoxic and anti-angiogenic properties of Cu(i) derivatives.

Homoleptic phosphino copper(I) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity.

The molecular electrostatic potential (MESP) V(r) data derived from a reliable quantum chemical method has been widely used for the interpretation and prediction of various aspects of chemical reactivity. A rigorous mapping of the MESP topology is achieved by computing both ∇V(r) data and the elements of the Hessian matrix at the critical points where ∇V(r) = 0. In the MESP topology, intra‐ and inter‐molecular bonded regions show the characteristic (3, −1) bond critical points (BCPs) while the electron‐rich regions such as lone pair and π‐bonds show (3, +3) minimum (Vmin) CPs. The Vmin analysis provides a simple and powerful technique to characterize the electron‐rich region in a molecular system as it corresponds to the condensed information of the wave function at this point due to the nuclei and electronic distribution through the Coulomb's law. The Vmin analysis has been successfully applied to explain the phenomena related to chemical reactivity such as π‐conjugation, aromaticity, substituent effect, ligand electronic effects, trans‐influence, redox potential, activation energy, cooperativity, noncovalent interactions, and so on. The MESP parameters ∆Vmin and ∆Vn, derived for arene systems have been used as powerful measures of substituent effects while Vmin at the lone pair region of ligands has been used as a reliable electronic parameter to assess their σ‐donating ability to metal centers. Furthermore, strong predictions on the intermolecular interactive behavior of molecular systems can be made from MESP topology studies. This review summarizes the chemical reactivity applications offered by MESP topology analysis for a large variety of organic, organometallic, and inorganic molecular systems.

Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity

Two glucose-derived thiourea derivatives, 2a and 2b, were prepared by addition of the corresponding amino sugars to a solution of 4-nitrobenzoyl isothiocyanate (Scheme 1). The thioureas were isolated as colorless solids in good yields and were fully characterized by NMR spectroscopy, optical rotation, elemental analysis, and also by single-crystal X-ray diffraction. Attempts to obtain CuII and NiII bis(chelate) complexes with these thioureas failed. However, the C(1)-protected thiourea derivative 2a reacted with orthopalladated acetato-bridged dimers to afford the corresponding monomeric PdII complexes 3 and 4 (Scheme 2). In these compounds, the thiourea coordinates to the metal as monoanionic O,S chelate ligand, which was confirmed by X-ray crystallography.

Michelle Sternberg

Papers

Synthesis and Metal Complexes of Thiourea Ligands Containing Carbohydrate‐Derived Substituents

2-Thia-1,3,5-triaza-7-phosphaadamantane-2,2-dioxide Revisited: Computational and Experimental Studies of a Neglected Phosphine