Electronegativity—a perspective

Electronegativity is a very useful concept but it is not a physical observable; it cannot be determined experimentally. Most practicing chemists view it as the electron-attracting power of an atom in a molecule. Various formulations of electronegativity have been proposed on this basis, and predictions made using different formulations generally agree reasonably well with each other and with chemical experience. A quite different approach, loosely linked to density functional theory, is based on a ground-state free atom or molecule, and equates electronegativity to the negative of an electronic chemical potential. A problem that is encountered with this approach is the differentiation of a noncontinuous function. We show that this approach leads to some results that are not chemically valid. A formulation of atomic electronegativity that does prove to be effective is to express it as the average local ionization energy on an outer contour of the atom’s electronic density.     

Compactin—a review

Compactin, a hypocholesterolemic molecule, is a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, which is a regulatory enzyme for cholesterol biosynthesis. The structural similarity and high affinity of the acid form of compactin and HMG, the natural substrate of enzyme, results in specific and effective inhibition of this enzyme. Inhibition results in reduced levels of mevalonic acid in the body, leading to pleiotropic effects. Various fungi have been used for the commercial production of compactin. Using different strategies for improving production levels, yields have been increased to around 900 times of the amount originally produced. Recently, the gene sequence responsible for compactin production has been cloned and sequenced. This review deals with the chemistry, mode of action, pharmacology, biosynthesis, and production of compactin. A comparative study of various reports dealing with the production of compactin is also included.     

Inflammation — a lifelong companion

Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.     

Nootkatone—a biotechnological challenge

Due to its pleasant grapefruit-like aroma and various further interesting molecular characteristics, (+)-nootkatone represents a highly sought-after specialty chemical. (+)-Nootkatone is accumulated in its producer plants in trace amounts only, and the demand of the food, cosmetics and pharmaceutical industry is currently predominantly met by chemical syntheses. These typically require environmentally critical reagents, catalysts and solvents, and the final product must not be marketed as a “natural flavour” compound. Both the market pull and the technological push have thus inspired biotechnologists to open up more attractive routes towards natural (+)-nootkatone. The multifaceted approaches for the de novo biosynthesis or the biotransformation of the precursor (+)-valencene to (+)-nootkatone are reviewed. Whole-cell systems of bacteria, filamentous fungi and plants, cell extracts or purified enzymes have been employed. A prominent biocatalytic route is the allylic oxidation of (+)-valencene. It allows the production of natural (+)-nootkatone in high yields under mild reaction conditions. The first sequence data of (+)-valencene-converting activities have just become known.

Polycarnitine—a new biomaterial

The natural product l-carnitine is—due to its biotechnological accessibility and specific properties—on the way to becoming an attractive biobased bulk product. l-Carnitine is a natural betaine with vitamin properties. Carnitine is an essential part of the fatty acid metabolism of human beings and animals. Carnitine was first isolated in 1905 from meat extract and important recent developments include the biosyntheses of l-carnitine from l-lysine or -butyrobetaine. Our synthesis routes are designed to maintain the primary structure and specific properties of carnitine, such as hydrophilicity and stiffening effects for polymeric structures and applications. l-Carnitine is converted via lactonization or olefinization into polymerizable basic molecules. The properties and the applications of carnitine polymers are described.This revised version was published online in February 2005 with text corrections in the subsection Biotechnological production of L-carnitine of the Introduction section.     

Pentosome — a new connective tissue component —is a subunit of amyloid P

Summary A new minute connective tissue structure, referred to as pentosome, has been investigated by electron microscopy and its nature has been examined by immunoperoxidase tests. Pentosomes are 3.5-nm wide, particulate structures that have been observed in the posterior chamber of the eye, the connective tissue spaces of the mouse foot-pad and the matrix of the mouse EHS tumor. They are usually found in the vicinity of microfibrils whether they are free or associated with elastic fibers. They tend to be organized into groups forming a three-dimensional semi-crystalline lattice at 10-nm intervals, but are connected by fine filaments. At high magnification, pentosomes appear as hollow structures composed of two parallel pentagons, which respectively measure 2.7 and 3.5 nm, and are held together by a cross-bar. A series of immunoperoxidase tests has only shown antigenicity against a serum protein, the amyloid P component. However, pentosomes are only about one-third the size of the 8.5-nm wide, disk-like segments of the amyloid P molecule. Since they could be subunits of these molecules, such subunits were prepared and compared with pentosomes; they appeared to be identical. It is concluded that the pentosomes found in connective tissue are AP subunits.     

Petroleum bioremediation — a multiphase problem

Microbial degradation of hydrocarbons is a multiphase reaction, involving oxygen gas, water-insoluble hydrocarbons, water, dissolved salts and microorganisms. The fact that the first step in hydrocarbon catabolism involves a membrane-bound oxygenase makes it essential for microorganisms to come into direct contact with the hydrocarbon substrate. Growth then proceeds on the hydrocarbon/water interface. Bacteria have developed two general strategies for enhancing contact with water-insoluble hydrocarbons: specific adhesion mechanisms and production of extracellular emulsifying agents. Since petroleum is a complex mixture of many different classes of hydrocarbons, of which any particular microorganism has the potential to degrade only part, it follows that the microorganisms must also have a mechanism for desorbing from used' oil droplets.The major limitations in bioremediation of hydrocarbon-contaminated water and soil is available sources of nitrogen and phosphorus. The usual sources of these materials, e.g. ammonium sulfate and phosphate salts, have a high water solubility which reduces their effectiveness in open systems because of rapid dilution. We have attempted to overcome this problem by the use of a new controlled-release, hydrophobic fertilizer, F-1, which is a modified urea-formaldehyde polymer containing 18% N and 10% P as P₂O₅. Microorganisms were obtained by enrichment culture that could grow on crude oil as the carbon and energy source and F-1 as the nitrogen and phosphorus source. The microorganisms and the F-1 adhered to the oil/water interface, as observed microscopically and by the fact that degradation proceeded even when the water phase was removed and replaced seven times with unsupplemented water — a simulated open system. Strains which can use F-1 contain a cell-bound, inducible enzyme which depolymerizes F-1.After optimizing conditions in the laboratory for the use of F-1 and the selected bacteria for degrading crude oil, a field trial was performed on an oil contaminated sandy beach between Haifa and Acre, Israel, in the summer of 1992. The sand was treated with 5 g F-1 per kg sand and inoculated with the selected bacteria; the plot was watered with sea water and plowed daily. After 28 days the average hydrocarbon content of the sand decreased from 5.1 mg per g sand to 0.6 mg per g sand. Overall, there was an approx. 86% degradation of pentane extractables as demonstrated by dry weight, I.R. and GLC analyses. An untreated control plot showed only a 15% decrease in hydrocarbons. During the winter of 1992, the entire beach (approx. 200 tons of crude oil) was cleaned using the F-1 bacteria technology. The rate of degradation was 0.06 mg g^-1 sand day^-1 (10°C) compared to 0.13 mg g^-1 sand day^-1 during the summer (25°C).     

Roflamycoin — a new channel-forming antibiotic

Ion permeability of lipid bilayers was studied in the presence of a new antifungal pentaene antibiotic, roflamycoin, the structure of which differs of which differs considerably from that of the well-known polyene channel-former amphotericin B. Both of them, however, show the property of increasing the membrane permeability only in the case of sterol-containing membrane when added on both its sides. The conductance is strongly dependent on the concentration of the antibiotic in the solutions and of sterol in the membrane. Unlike the amphotericin B channels, roflamycoin channels are potential-dependent and have short lifetime (approx. 1 s) and high conductance (approx. 100 ps in 1 M KCl), which increases linearly with the salt concentration and is not blocked by the familiar blockers of amphotericin B channels. The two antibiotics seem to have a common mechanism of channel formation, viz. the formation starts from two semi-pores assembled in the opposite monolayers from several molecules of the antibiotic and sterol. However, the inner diameter of the roflamycoin channel is larger because of the different antibiotic-to-sterol ratio in the channel aggregate. It is believed that the difference in the ratio is due to the presence of the methyl group in the polyene chain of roflamycoin, and the considerable difference in lifetimes of the two types of channels depends on the terminal groups of the antibiotics.     

Tricin—a potential multifunctional nutraceutical

This review throws light on the natural occurrence and distribution of tricin (5,7,4′-trihydroxy-3′,5′-dimethoxyflavone) and its conjugated forms, as more common natural plant constituents than previously known. It examines the current literature dealing with its biosynthesis, regulation, biological significance, pharmacological effects, and potential role as a chemopreventive and anticancer agent. Because of its common occurrence in cereal grain plants and the wide spectrum of its health promoting effects, a metabolic engineering strategy is proposed to produce tricin in sufficient amounts for further experimentation, and increase its accumulation in wheat grain endosperm as a nutraceutical.     

Brucellosis in India — a review

Brucellosis is an important re-emerging zoonosis with a worldwide distribution. It is still an uncontrolled serious public health problem in many developing countries including India. Brucellosis in India is yet a very common but often neglected disease. Currently, Brucella melitensis accounts for most recorded cases globally with cattle emerging as a important reservoir with the few cases of B. suis. Isolated cases of non-terrestrial brucellosis and continuing transmission from wild animals have raised important epidemiological issues. Routine serological surveillance along with high clinical suspicion and screening of family members of index cases would be essential in delineating the real magnitude of human brucellosis in endemic countries. Increased business and leisure travel to endemic countries have led to diagnostic challenge in non-endemic areas. Laboratory testing is indispensable for diagnosis. Advances in newer rapid, sensitive, and specific testing methodologies and alternate treatment strategies are urgently needed. A safe and effective vaccine in human is not yet available. Prevention is dependent upon increasing public awareness through health education programmes and safe livestock practices. Active co-operation between health and veterinary services should be promoted. This review collates world literature and its impact to the discovery, isolation and diagnosis and epidemiology along with the control measures adapted in the Indian scenario.     

LIMS — a catalyst for re-engineering

This paper describes how a laboratory information management system (LIMS) can act as a catalyst for re-engineering. Some of the key issues of successful change management are described and the common pitfalls that LIMS projects can fall into are summarised.     

Glycosidases—a great synthetic tool

Glycosidases were used to prepare oligosaccharide structures of physiological and medicinal relevance. The study included an extensive screening of crude enzymatic preparations for α- and β-galactosidase, α- and β-mannosidase, β-N-acetylglucosaminidase, β-N-acetylgalactosaminidase and α-l-fucosidase activities. The enzymes were assessed with respect to regioselectivity of glycosyl transfer on to carbohydrate acceptors. The purification procedures for individual biocatalysts are described in detail.