Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

Direct and indirect modulation of neuropeptide Y gene expression in response to hypoglycemia in rat arcuate nucleus

AbstractExpression of neuropeptide Y (Npy) heteronuclear (hn) RNA, an indicator of gene transcription, was significantly increased in the arcuate nucleus of rats 30min after insulin injection. Npy hnRNA levels were also increased significantly in response to hypoglycemia in rats in which the hypothalamus was deafferentated, although the absolute levels were significantly lower than in sham-operated rats. Direct effects of lowering glucose levels on Npy gene expression were also confirmed in hypothalamic organotypic cultures. Thus, Npy gene transcription in the arcuate nucleus increases rapidly in response to hypoglycemia, and both direct and indirect inputs are involved in the rapid upregulation

A thorough anion-π interaction study in biomolecules:On the importance of cooperativity effects

Noncovalent interactions have a constitutive role in the science of intermolecular relationships, particularly those involving aromatic rings such as π-π and cation-π. In recent years, anion-π contact has also been recognized as a noncovalent bonding interaction with important implications in chemical processes. Yet, its involvement in biological processes has been scarcely reported. Herein we present a large-scale PDB analysis of the occurrence of anion-π interactions in proteins and nucleic acids. In addition we have gone a step further by considering the existence of cooperativity effects through the inclusion of a second noncovalent interaction, i.e. π-stacking, T-shaped, or cation-π interactions to form anion-π-π and anion-π-cation triads. The statistical analysis of the thousands of identified interactions reveals striking selectivities and subtle cooperativity effects among the anions, π-systems, and cations in a biological context. The reported results stress the importance of anion-π interactions and the cooperativity that arises from ternary contacts in key biological processes, such as protein folding and function and nucleic acids-protein and protein-protein recognition. We include examples of anion-π interactions and triads putatively involved in enzymatic catalysis, epigenetic gene regulation, antigen-antibody recognition, and protein dimerization

Structures and Spin States of Crystalline [Fe(NCS)2L2] and [FeL3]2+ Complexes (L = an Annelated 1,10-Phenanthroline Derivative)

The phase behaviour and spin states of [Fe(NCS)2(dpq)2] (1; dpq = dipyrido[3,2-f:2′,3′-h]quinoxaline), [Fe(NCS)2(dppz)2] (2; dppz = dipyrido[3,2-a:2′3′-c]phenazine) and [Fe(NCS)2(dppn)2] (3; dppn = dipyrido[3,2-a:2′3′-c]benzophenazine) have been investigated. Solvent-free 1 and 2 are isostructural and low-spin in the crystalline state, in contrast to previously published 2·py (py = pyridine) which exhibits a hysteretic spin-crossover (SCO) transition near 140 K. The inactivity of 1 and 2 towards SCO may relate to their more crowded intermolecular lattice environment, particularly two very short intermolecular anion⋯π contacts involving the NCS− ligands. Two solvate phases of 1 are also described, including 1·2py which undergoes gradual SCO with T½ca. 188 K. Bulk samples of 2 and 3 are predominantly low-spin and isostructural with the crystals of 2 by powder diffraction, but bulk samples of 1 contain an extra phase that exhibits hysteretic SCO, but was not crystallographically characterised. Crystal structures of low-spin [Fe(dppz)3][ClO4]2 (4) and a solvate of [Fe(dppn)3][BF4]2 (5) are also described, which are the first homoleptic complexes of these ligands to be crystallographically characterised

Au I Cl-bound N-heterocyclic carbene ligands form MII4(LAuCl) 6 integrally gilded cages

The incorporation of an N-heterocyclic carbene (NHC) moiety into a self-assembled MII4L6 cage framework required the NHC first to be metallated with gold(I). Bimetallic cages could then be constructed using zinc(II) and cadmium(II) templates, showing weak luminescence. The cages were destroyed by the addition of further gold(I) in the form of AuI(2,4,6-trimethoxybenzonitrile)2SbF6, which caused the reversibly-formed cages to disassemble and controllably release the AuI-NHC subcomponent into solution. This release in turn induced the growth of gold nanoparticles. The rate of dianiline release could be tuned by capsule design or through the addition of chemical stimuli, with different release profiles giving rise to different nanoparticle morphologies

Noncovalent Lone Pair⋅⋅⋅(No-π!)-Heteroarene Interactions: The Janus-Faced Hydroxy Group

A comparative study by NMR using designed top pan molecular balances demonstrates that the noncovalent interaction of a hydroxyl group with π-deficient pyrazine and quinoxaline units involves a lone pair•••heteroarene interaction which is much stronger and essentially solvent independent when measured relative to the classical π-facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene