Current Inorganic Chemistry (v.2, #1)

We live in what one author of this Hot Topic issue has correctly labeled “the Age of Aluminum” [1]. Aluminum, the third most abundant element in the Earth's crust and the most abundant metal, is one of the most remarkable elements in the periodic table. Compounds made with aluminum are strong, durable, light and corrosion resistant. Aluminum is also an excellent conductor of electricity. For these reasons, aluminum currently finds its way into virtually every aspect of our daily lives. Industrially, aluminum is used in cans and cookware, aluminum foil, housing materials, components of electrical devices, airplanes, boats, cars and numerous hardware items of all descriptions. Aluminum is found in drinking water, as a food additive in typical Western diets, cosmetics, pharmaceutical products and because of such ubiquity, it is increasingly found in our bodies [2, 3]. None of this would necessarily be a problem if aluminum was inert in biological systems. However, in spite of a widely held belief that this is true, it is demonstrably not the case. Aluminum is highly reactive with oxygen and carbon, two of the most abundant organic elements, yet appears to have no intrinsic nor beneficial role in organic chemistry of any biota on the planet [1]. Instead, evidence clearly shows that aluminum is toxic to plants, animals and humans. For example, aluminum intoxication frequently impairs learning, memory, concentration and behaviour in both animals and humans. The latter is typically reflected in confusion, anxiety, repetitive behaviours and sleep disturbances. Notably, all of these symptoms typical of an aluminum overload are also typical to two most common neurological disorders of the Western world, one neurodegenerative and the other one neurodevelopmental: Alzheimer's disease and autism. Moreover, there is now sufficient experimental evidence implicating elevated levels of aluminum in both of these disease conditions [2, 4, 6]. In this Hot Topic issue of Current Inorganic Chemistry we have brought together some of the world's experts on the biochemistry of aluminum to consider the potential impacts of aluminum compounds on human health. The issue starts with a discussion of aluminum

Elucidating Aluminium's Exposome by Christopher Exley (3-7).
The term exposome has been coined to express the totality of environmental or an environmental exposure (Wild, C.P. Cancer Epidemiol. Biomarkers Prev., 2005 14, 1847-1850). The biologically non-essential and environmentally ubiquitous element aluminium is arguably the most significant metal toxicant in the lithosphere and it is imperative that its exposome is as fully understood as possible. Identifying the tools required to elucidate and illuminate aluminium

There is a burgeoning body of evidence that aluminum can be implicated as an etiological factor of several neuropathological events. The molecular mechanisms underlying aluminum toxicity are still poorly understood. Reflecting on many studies, we suggest a new view on the toxicity of aluminum in a link with fluoride. Soluble aluminofluoride complexes - fluoroaluminate (AlFx) are formed in water solutions containing fluoride and traces of aluminum. These complexes are able to simulate phosphate groups in many biochemical reactions. AlFx are used in many laboratory investigations of guanine nucleotide binding proteins (G proteins). They affect various enzyme activities and cell signaling cascades. The hidden danger of a long-term synergistic action of aluminum and fluoride is not fully recognized at this point. We suggest that aluminum and fluoride can exacerbate the pathological and clinical problems, namely by interfering with a great number of G-protein-dependent cellular mechanisms, and by worsening excitotoxicity, microglial priming, and brain inflammation. Our suggestion opens the door to a better understanding of mechanisms of aluminum harmful effects on human health.

Aluminum (Al) is a recognized neurotoxin causally linked to several neurodegenerative diseases with a dementia component. Al has long had a GRAS (Generally Recognized As Safe) rating by the US FDA, that allows Al salts to be used in food manufacture and clarification of urban drinking water supplies. Routine ingestion of Al salts throughout life causes bioavailable Al to accumulate in the brain where it specifically deposits in regions most vulnerable in Alzheimer's disease (AD). AD has an insidious onset, developing slowly and progressively, producing cognitive deterioration in old age. The main source of Al exposure for humans is their total dietary Al intake from foods, water, other beverages, and Al additives. Prospective data collection from epidemiological studies attempting to quantify total dietary Al intake, to probe for AD causality, is virtually impossible to obtain in a human population where all its members are routinely exposed to abundant Al amounts from many sources. Longitudinal animal studies provide a parallel in that their feed and water intakes can be rigorously controlled throughout the life span. Such a study revealed that a significant proportion of rats, particularly those that consumed Al in an equivalent amount to the high end of the human total dietary Al range, progressively accumulated Al in their brain, accompanied by AD-related neuropathology and cognitive deterioration in old age. This article describes evidence for the close involvement of Al with the major AD hallmarks and provides suggestions that may help to remediate the current AD epidemic in westernized countries.

The environmental presence of aluminium (Al) is widespread and a significant human absorption of Al salts occurs by way of diet and drinking water. Whether this can affect the incidence and progression of age-related neurological diseases, notably Alzheimer's disease remains controversial. However, there are increasing indications that Al can cause inflammatory changes within the central nervous system both in humans and in experimental animals. It is also known that basal levels of immune activation are elevated within the aging brain even in the absence of recognized inflammatory stimuli. Since, following activation, the immune system of the brain is unable to rapidly return to basal levels, this may in part reflect an accumulation of the lifespan history of the organism's immune responses. Even greater levels of inflammatory activity are found in brains of those suffering from several types of distinct neurodegenerative disorders. Since most of these disorders are idiopathic and not strongly linked to a specific genetic trait, it must be assumed that environmental factors can initiate or advance the development of such disorders. Data from experimental animals and from post-mortem human tissue, together with epidemiological evidence, make Al a strong candidate for being a significant contributor to overall incidence of more than one neurodegenerative disorder.

A great deal has been learned about the neurotoxicity of aluminum over the past two decades in terms of its ability to disrupt cellular function. Newer evidence suggests that a more central pathophysiological mechanism may be responsible for much of the toxicity of aluminum and aluminofluoride compounds on the brain. This mechanism involves activation of the brain

The chemical forms (species) of aluminum in blood plasma and brain extracellular fluid are considered, as they are the candidates for brain aluminum uptake and efflux. The blood-brain barrier is the primary site of brain aluminum uptake. The mechanism of brain uptake of aluminum transferrin, long thought to be mediated by transferrin-receptor mediated endocytosis, requires further investigation. Brain Al citrate uptake has been attributed to the sodium-independent Lglutamate/ L-cystine exchanger system, system Xc-. Reports have suggested aluminum can compromise blood-brain barrier integrity, however the studies were conducted with aluminum concentrations greatly exceeding those seen in human blood plasma. Aluminum appeared in cerebrospinal fluid suggesting it can cross the choroid plexus and in brain after intranasal application suggesting it can be taken up by cranial nerves, but neither of these routes has been definitively demonstrated. Brain aluminum efflux appears to be carrier-mediated, however the mechanism has not been identified. A small increase in brain aluminum seems sufficient to produce neurotoxicity. Once aluminum enters the brain it persists there for a very long time; estimates of the half-life range from 20% of the lifespan to greater than the lifespan. Al persistence in bone, which maintains the majority of the body burden, may influence brain Al, due to equilibrium among the body's organs. Chelation therapy with desferrioxamine has been shown to reduce some manifestations of aluminum toxicity although it may increase redistribution of aluminum to the brain to increase aluminum-induced neurotoxicity. An orally-effective aluminum chelator that is an improvement over desferrioxamine has not yet been demonstrated. Although a non-essential metal, there are mechanisms enabling aluminum to get into the brain, accumulating over the lifespan, and creating the potential to contribute to many neurodegenerative disorders.

The main challenges in the modern synthesis prompt the method development by using iron catalysts. The functionalization of unactivated C-H bonds has been a focal point of experimental and theoretical research and play important roles among these synthesis routes. In iron-catalyst C-H activations, ferric and ferrous salts catalyzed various types C-H bonds, for example sp C-H, sp2 C-H and sp3 C-H, have been studied extensively. Iron-catalyzed C-H bonds transformation are employed in the design of even more active excellent catalysts and stereospecific organic compounds. However, the fundamental understanding of structure and reactivity is rather limited. The review covers the booming developments in the past couples of years and provides a deeper insight of the reaction complexity. This review would give a positive impact on the applications in industry, natural products, pharmacy, and bioactive compounds on the next generation of chemical syntheses.

The chromic acid oxidation of formic acid in the presence and absence of bipyridine (bpy) as a catalyst have been studied in aqueous micellar media under the kinetic condition, [formic acid]T > > [Cr(VI)]T at various temperatures. The un catalyzed path is first order with respect to [H+], [formic acid]T and [Cr(VI)]T. The bpy catalyzed path gives also first order dependency on [H+]. This path also shows a first order dependence on [bpy]T. HCrO4 - has been found to be kinetically active in the absence of bpy while in the bpy catalyzed path, a Cr(VI)-bpy complex was considered to be the active oxidant. In this path the Cr(VI)-bpy complex undergoes a nucleophilic attack by the formic acid to form a ternary complex which subsequently experiences a redox decomposition involving 3e transfer leading to CO2 and corresponding Cr(IV)-bpy complex. In the un catalyzed path, the Cr(VI)-substrate ester undergoes acid-catalyzed redox decomposition through 3e-transfer as the rate-determining step. All these patterns remain unaltered in the presence of externally added surfactants. The effects of an anionic surfactant, sodium dodecyl sulphate (SDS), on both the un catalyzed and catalyzed paths were studied.