Andrew D. Phillips

Polynuclear Ruthenium, Osmium and Gold Complexes. The Quest for Innovative Anticancer Chemotherapeutics

Polynuclear compounds are a relatively new and successful approach in metal-based cancer chemotherapy as typified by the trinuclear Pt compound BBR3464 which was evaluated in clinical trials. In this review, we discuss newer developments of polynuclear ruthenium, osmium and gold complexes, focusing on their anticancer activity. The compounds presented are often supposed to exert their anticancer activity by different modes of action as compared to established drugs, including newly proposed mechanisms such as enzyme inhibition, crosslinking of biomacromolecules or through photo-activation, though many of the examples are also capable of binding to DNA nucleobases. Important metabolization and chemical characteristics of such compounds are discussed, and if the appropriate data is available, molecular modes of action are highlighted.

A main-group donor-acceptor adduct: 1,3,4,5-tetramethylimidazol-2-ylidene-tris(pentafluorophenyl)borane.

The solid-state structural analysis of the title compound, Me4C2N2C-->B(C6F5)3 or C25H12BF15N2, provides useful metric parameters for the qualitative comparison of the donor strength with other mono- and dicoordinate main-group compounds which feature distinctive lone-pair character.

Models for Bonding in the Alkali Metal-Gallium Clusters K2Ga4(C6H3-2,6-Trip2)2 and Na2Ga4Trip6 (Trip=C6H2-2,4,6-i-Pr3): Importance of Alkali Metal-Aryl Interactions

Computational data for the tetragallium clusters K2Ga4(C6H3-2,6-Trip2)2 and Na2Ga4Trip6 (Trip=C6H2-2,4,6-i-Pr3) showed that significant Ga–Ga multiple bonding exists only in the latter species. The data for the M2Ga4R2 (M=Li, Na or K; R=H, Me or Ph) models of K2Ga4(C6H3-2,6-Trip2)2, which has a distorted octahedral K2Ga4 core structure incorporating an almost square Ga4 moiety, showed that they have an occupied bonding π-orbital that is delocalized over the four galliums, thereby conferring formal aromatic character by the [4n+2] Hückel rule. However, the Ga–Ga bond order is approximately one, and the hypothetical free [Ga4H2]2− dianion is unstable toward electron dissociation. For the cluster Na2Ga4Trip6, calculations for the model compounds Ga4H6 and [Ga4H6]2−, which involve a central gallium trigonally substituted by three GaH2 units, confirmed that no multiple bonding exists in the neutral species Ga4H6 but that, upon reduction to [Ga4H6]2−, a π-bond is formed which is delocalized over the Ga4 unit. The Ga–Ga distances that were calculated for all model species listed above are longer than those experimentally observed. This was attributed to the absence of alkali metal-aryl interactions in the model species.

Towards the design of novel boron- and nitrogen-substituted ammonia-borane and bifunctional arene ruthenium catalysts for hydrogen storage

Electronic‐structure density functional theory calculations have been performed to construct the potential energy surface for H2 release from ammonia‐borane, with a novel bifunctional cationic ruthenium catalyst based on the sterically bulky β‐diketiminato ligand (Schreiber et al., ACS Catal. 2012, 2, 2505). The focus is on identifying both a suitable substitution pattern for ammonia‐borane optimized for chemical hydrogen storage and allowing for low‐energy dehydrogenation. The interaction of ammonia‐borane, and related substituted ammonia‐boranes, with a bifunctional η6‐arene ruthenium catalyst and associated variants is investigated for dehydrogenation. Interestingly, in a number of cases, hydride‐proton transfer from the substituted ammonia‐borane to the catalyst undergoes a barrier‐less process in the gas phase, with rapid formation of hydrogenated catalyst in the gas phase. Amongst the catalysts considered, N,N‐difluoro ammonia‐borane and N‐phenyl ammonia‐borane systems resulted in negative activation energy barriers. However, these types of ammonia‐boranes are inherently thermodynamically unstable and undergo barrierless decay in the gas phase. Apart from N,N‐difluoro ammonia‐borane, the interaction between different types of catalyst and ammonia borane was modeled in the solvent phase, revealing free‐energy barriers slightly higher than those in the gas phase. Amongst the various potential candidate Ru‐complexes screened, few are found to differ in terms of efficiency for the dehydrogenation (rate‐limiting) step. To model dehydrogenation more accurately, a selection of explicit protic solvent molecules was considered, with the goal of lowering energy barriers for H‐H recombination. It was found that primary (1°), 2°, and 3° alcohols are the most suitable to enhance reaction rate.

Formation of [Ar*Ge{CH2C(Me)C(Me)CH2}CH2C(Me)]2 (Ar* = C6H3-2,6-Trip2; Trip = C6H2-2,4,6-i-Pr3) via reaction of Ar*GeGeAr* with 2,3-dimethyl-1,3-butadiene: evidence for the existence of a germanium analogue of an alkyne

The reduction of Ar*GeCl (Ar* = C6H3-2,6-Trip2; Trip = C6H2-2,4,6-i-Pr3) with one equivalent of potassium leads to the formation of a germanium analogue of an alkyne Ar*GeGeAr* 1; reaction of 1 with 2,3-dimethyl-1,3-butadiene yields [Ar*Ge(CH2C(Me)C(Me)CH2)CH2C(Me)=]2 2, which was structurally characterized.

Nitrogen ligands on a phosphinic Lewis acceptor including a 2,2′-dipyridyl chelate complex

In the context of the developing coordination chemistry of lone pair bearing phosphinic centers as acceptors, synthesis and characterisation for new complexes of the phosphadiazonium cation with nitrogen donors are described, including the first dipyridyl chelate.

Isolation and comprehensive solid state characterization of Cl3Al–O–PCl3

The crystal structure of Cl3Al–O–PCl3 contains covalent molecular units with an essentially linear Al–O–P axis, and a similar solution structure is indicated by NMR spectroscopy.

Water-Soluble Silver(I) Complexes Featuring the Hemilabile 3,7-Dimethyl-1,3,5-triaza-7-phosphabicyclo[3.3.1]nonane Ligand: Synthesis, Characterization, and Antimicrobial Activity

This paper describes the preparation and comprehensive characterization of a series of water-soluble cationic silver(I)-centered complexes featuring the hemilabile P, N-ligand known as 3,7-dimethyl-1,3,5-triaza-7-phosphabicyclo[3.3.1]nonane (herein abbreviated as PTN(Me)) and differing types of monoanionic counterions including known biologically active sulfadiazine and triclosan. The complexes primarily differed though the number of coordinating PTN(Me) ligands. The bis-substituted Ag(I) complexes revealed P, N bidentate coordination, while the only P-monocoordination of the metal center was observed for the tris-substituted systems. The bis-ligated silver compounds were observed to quickly degrade upon photoexposure or in contact with air. In contrast, the tris-ligated complexes demonstrated greater stability, in particular, a high resistance to photo-decomposition. Calculated geometry optimized models using the density functional theory method (BP86) revealed for the bis-substituted PTN(Me) Ag(I) species that the total enthalpy of the tetrahedral C2-symmetric structure is marginally lower by -0.6 kcal mol-1 compared to the planar C2 h structure, which is analogous for the corresponding [Au(PTN(Me))2]+ complex with Δ H = -0.5 kcal mol-1. Hence both types of complexes feature free rotation of the PTN ligand about the M-P bond axis. This series of Ag(I) and bis-PTN(Me) Au(I) complexes were evaluated using the agar well diffusion test for potential antimicrobial and antifungal activity. The nature of the counterion was found to have a strong correlation with the area of microbiological growth inhibition. Silver(I) complexes bearing the deprotonated triclosan as the counterion demonstrated the greatest activity, with large zones of growth inhibition, with the tris-ligated triclosan complex obtaining of a high clearance of 42 mm against the Gram-negative Escherichia coli. In contrast, the previously reported [Au(PTN(Me))2]Cl complex demonstrated activity only against E. coli, which is lower than that observed for the silver(I) PTN(Me) species.