Organoiridium complexes : anticancer agents and catalysts

Iridium is a relatively rare precious heavy metal, only slightly less dense than osmium. Researchers have long recognized the catalytic properties of square-planar Ir(I) complexes, such as Crabtree's hydrogenation catalyst, an organometallic complex with cyclooctadiene, phosphane, and pyridine ligands. More recently, chemists have developed half-sandwich pseudo-octahedral pentamethylcyclopentadienyl Ir(III) complexes containing diamine ligands that efficiently catalyze transfer hydrogenation reactions of ketones and aldehydes in water using H2 or formate as the hydrogen source. Although sometimes assumed to be chemically inert, the reactivity of low-spin 5d(6) Ir(III) centers is highly dependent on the set of ligands. Cp* complexes with strong σ-donor C^C-chelating ligands can even stabilize Ir(IV) and catalyze the oxidation of water. In comparison with well developed Ir catalysts, Ir-based pharmaceuticals are still in their infancy. In this Account, we review recent developments in organoiridium complexes as both catalysts and anticancer agents. Initial studies of anticancer activity with organoiridium complexes focused on square-planar Ir(I) complexes because of their structural and electronic similarity to Pt(II) anticancer complexes such as cisplatin. Recently, researchers have studied half-sandwich Ir(III) anticancer complexes. These complexes with the formula [(Cp(x))Ir(L^L')Z](0/n+) (with Cp* or extended Cp* and L^L' = chelated C^N or N^N ligands) have a much greater potency (nanomolar) toward a range of cancer cells (especially leukemia, colon cancer, breast cancer, prostate cancer, and melanoma) than cisplatin. Their mechanism of action may involve both an attack on DNA and a perturbation of the redox status of cells. Some of these complexes can form Ir(III)-hydride complexes using coenzyme NAD(P)H as a source of hydride to catalyze the generation of H2 or the reduction of quinones to semiquinones. Intriguingly, relatively unreactive organoiridium complexes containing an imine as a monodentate ligand have prooxidant activity, which appears to involve catalytic hydride transfer to oxygen and the generation of hydrogen peroxide in cells. In addition, researchers have designed inert Ir(III) complexes as potent kinase inhibitors. Octahedral cyclometalated Ir(III) complexes not only serve as cell imaging agents, but can also inhibit tumor necrosis factor α, promote DNA oxidation, generate singlet oxygen when photoactivated, and exhibit good anticancer activity. Although relatively unexplored, organoiridium chemistry offers unique features that researchers can exploit to generate novel diagnostic agents and drugs with new mechanisms of action

The role of venture capitalists in the regional innovation ecosystem : a comparison of networking patterns between private and publicly backed venture capital funds

This paper empirically examines the development of social networks among venture capitalists and other professionals of the regional innovation ecosystem. Using an online survey of venture capitalists, the article considers their networking behaviour, focusing particularly on the distinction between those employed by private and those employed by publicly backed venture capital funds, and on the composition and spatial search of their networks. It investigates whether the frequency of interaction between venture capitalists and other members of the innovation ecosystem is associated with the nature of the venture capital funds. The paper provides the first detailed investigation of the relationship between different types of venture capitalists and other players of the innovation ecosystem such as universities incubators, research institutes, and business support organisations. The results show that there are distinctive differences within the two seemingly similar professional groups (private and public venture capitalists), and public dependence of the venture capital fund is strongly and significantly associated with higher volumes of interactions. The more publicly dependent a fund is, the more it interacts with other players of the innovation system. This finding has important implications for both academics and practitioners and suggests that publicly backed funds have a wider role to play in mobilising the different players of the regional innovation ecosystem

Cultural economy and the creative field of the city

I begin with a rough sketch of the incidence of the cultural economy in US cities today. I then offer a brief review of some theoretical approaches to the question of creativity, with special reference to issues of social and geographic context. The city is a powerful fountainhead of creativity, and an attempt is made to show how this can be understood in terms of a series of localized field effects. The creative field of the city is broken down (relative to the cultural economy) into four major components, namely, (a) intra-urban webs of specialized and complementary producers, (b) the local labor market and the social networks that bind workers together in urban space, (c) the wider urban environment, including various sites of memory, leisure, and social reproduction, and (d) institutions of governance and collective action. I also briefly describe some of the path-dependent dynamics of the creative field. The paper ends with a reference to some issues of geographic scale. Here, I argue that the urban is but one (albeit important) spatial articulation of an overall creative field whose extent is ultimately nothing less than global

Corporate Power and Social Policy: The Political Economy of the Transnational Tobacco Companies.

Drawing on published tobacco document research and related sources, this article applies Farnsworth and Holden's conceptual framework for the analysis of corporate power and corporate involvement in social policy (2006) to the transnational tobacco companies (TTCs). An assessment is made of TTCs' structural power, the impact upon their structural position of tobacco control (TC) policies, and their use of agency power. The analysis suggests that, as a result of the growth of TC policies from the 1950s onwards, TTCs have had to rely on political agency to pursue their interests and attempt to reassert their structural position. The collapse of the Eastern bloc and the liberalisation of East Asian economies presented new structural opportunities for TTCs in the 1980s and 1990s, but the development of globally coordinated TC policies facilitated by the World Health Organisation's Framework Convention on Tobacco Control has the potential to constrain these

Promotion of Iridium-Catalyzed Methanol Carbonylation: Mechanistic Studies of the Cativa Process

The iridium/iodide-catalyzed carbonylation of methanol to acetic acid is promoted by carbonyl complexes of W, Re, Ru, and Os and simple iodides of Zn, Cd, Hg, Ga, and In. Iodide salts (LiI and Bu4NI) are catalyst poisons. In situ IR spectroscopy shows that the catalyst resting state (at H2O levels ≥ 5% w/w) is fac,cis-[Ir(CO)2I3Me]-, 2. The stoichiometric carbonylation of 2 into [Ir(CO)2I3(COMe)]-, 6, is accelerated by substoichiometric amounts of neutral promoter species (e.g., [Ru(CO)3I2]2, [Ru(CO)2I2]n, InI3, GaI3, and ZnI2). The rate increase is approximately proportional to promoter concentration for promoter:Ir ratios of 0−0.2. By contrast anionic Ru complexes (e.g., [Ru(CO)3I3]-, [Ru(CO)2I4]2-) do not promote carbonylation of 2 and Bu4NI is an inhibitor. Mechanistic studies indicate that the promoters accelerate carbonylation of 2 by abstracting an iodide ligand from the Ir center, allowing coordination of CO to give [Ir(CO)3I2Me], 4, identified by high-pressure IR and NMR spectroscopy. Migratory CO insertion is ca. 700 times faster for 4 than for 2 (85 °C, PhCl), representing a lowering of ΔG by 20 kJ mol-1. Ab initio calculations support a more facile methyl migration in 4, the principal factor being decreased π-back-donation to the carbonyl ligands compared to 2. The fac,cis isomer of [Ir(CO)2I3(COMe)]-, 6a (as its Ph4As+ salt), was characterized by X-ray crystallography. A catalytic mechanism is proposed in which the promoter [M(CO)mIn] (M = Ru, In; m = 3, 0; n = 2, 3) binds I- to form [M(CO)mIn+1]-H3O+ and catalyzes the reaction HI(aq) + MeOAc → MeI + HOAc. This moderates the concentration of HI(aq) and so facilitates catalytic turnover via neutral 4