Volume 9, Issue 1-4 - Special issue: Medicinal Redox Inorganic Chemistry

Texaphyrins, first prepared by Sessler and coworkers in the 1980s, represent early examples of expanded porphyrins. This class of pentaaza, oligopyrrolic macrocycles demonstrates excellent tumor localization and metal-chelating properties. In biological milieus, texaphyrins act as redox mediators and are able to produce reactive oxygen species. Furthermore, texaphyrins have been shown to upregulate zinc in vivo , an important feature that inspired us to develop new zinc ionophores that might allow the same function to be elicited but via a simpler chemical means. In this review, the basic properties of texaphyrins and the zinc ionophores they helped spawn will be discussed in the cadre of developing an understanding that could lead to the preparation of new, redox-active anticancer agents.

Macrophages sense exogenous/endogenous danger signals due to their high functional plasticity and adjust their output signals accordingly. These comprise immune responses with the formation of reactive oxygen species, nitric oxide and pro-inflammatory cytokines, with the assumption that reactive species compose a redox signalling network. However, alternatively polarised macrophages suppress toxic radical formation, producing anti-inflammatory signatures associated with tissue repair, immune modulation, and angiogenesis. To change their mediator profile, we describe macrophage subsets and their response to apoptotic cells, focusing on reactive oxygen/nitrogen species and signalling mechanisms, and how apoptotic cells polarise macrophages to adopt an immune-regulatory, pro-angiogenic, and tumour-promoting phenotype.

Cystathionine β-synthase (CBS) catalyzes the condensation of homocysteine with serine or cysteine to form cystathionine and H 2 O or H 2 S. Human CBS has a non-catalytic heme bound to cysteine and histidine. The heme environment is conserved among several eukaryotic species but does not resemble any other protein. Fe(III)-CBS is relatively unreactive; however, reduction to Fe(II)-CBS can be achieved by strong chemical and biochemical reductants. Once reduced, Fe(II)-CBS can react with CO, which leads to a carbonylated and inactive species. Fe(II)-CBS can also be reoxidized by oxygen back to Fe(III)-CBS, thus forming superoxide radical. Kinetic considerations favor reoxidation unless this occurs under very low oxygen concentrations.

This review aims to clarify (1) what is a true mimic of superoxide dismutase family of enzymes, SOD; and (2) whether such compound could act as SOD mimic in a complex biological milieu. Several groups of compounds (metalloporphyrins, metallocorroles, Mn biliverdins, Mn cyclic polyamines, Mn salens, and metal oxides and salts) have been described. Their ability to catalyze the dismutation of O 2 ·– , [ k cat (O 2 ·– )], thermodynamic property that supports high catalytic ability ( E 1/2 ), kinetic factors that facilitate the catalysis, and the stability of compounds, which assures the integrity of metal coordination sphere where reactions of interest occur have been discussed. The other possible in vivo actions of those compounds, such as peroxynitrite and hypochlorite reduction, peroxidase-like activity, thiol oxidase activity etc., have been described as well. Based on in vivo studies it appears that k cat (O 2 ·– ) for Mn(III) N-substituted pyridylporphyrins parallels their therapeutic ability. The reason for that lies in their electrophilic nature which favors reactions with nucleophilic (anionic) reactive species (O 2 ·– , ONOO – , ClO – , HO 2 – , CO 3 ·– ) and simple or protein thiolates. Their in vivo multiple rather than single modes of actions, would be determined by: (a) their redox properties; (b) localization at targeted cellular site; and (c) redox environment of diseased or mutated/cancer cell. Quality of any drug preparation and the knowledge of researchers on its properties are essential when its mechanistic aspects are explored.

Inorganic radicals, such as superoxide and hydroxyl, play an important role in biology. Their tendency to oxidize or to reduce other compounds has been studied by pulse radiolysis; electrode potentials can be derived when equilibrium is established with a well-known reference compound. An IUPAC Task Group has evaluated the literature and produced the recommended standard electrode potentials for such couples as (O 2 /O 2 ·- ), (HO · , H + /H 2 O), (O 3 /O 3 ·- ), (Cl 2 /Cl 2 ·- ), (Br 2 ·- /2Br - ), (NO 2 · /NO 2 - ), and (CO 3 ·- /CO 3 2- ).