Rationalization of the strength of metal binding to human serum transferrin

A wide range of metal ions of natural, therapeutic, diagnostic and toxic interest are transported by serum transferrin (80 kDa). It is therefore important to understand the factors that control the strength of metal binding. We show here that even though Sc3+ has only slightly larger ionic radius than Fe3+ (0.075 nm versus 0.065 nm), it binds to the C-lobe and N-lobe sites much more weakly: logK1* (bicarbonate-independent binding constant) 14.6 +/- 0.2, logK2* 13.3 +/- 0.3, respectively (10 mM Hepes, 5 mM bicarbonate, 310 K). Preferential binding to the C-lobe was established by 1H-NMR spectroscopy. We show that the strength of binding of divalent and trivalent metal ions to human serum transferrin correlates with metal ion acidity [and therefore with the strength of binding to hydroxide, K1(OH)]. The correlations are of predictive value for a range of other metal ions. The plot of logK1* (human serum transferrin) versus logK1(OH) has a negative intercept consistent with unfavorable entropy effects due to lobe closure of apotransferrin on binding of metal ions. This interpretation was tested by comparison with similar correlations of the strength of metal binding to the enzymes carbonic anhydrase and carboxypeptidase with that for the low-M(r) ligand imidazole. These plots have positive intercepts consistent with the preorganized (entatic) state of these metalloenzymes (favorable entropy effects on metal binding).     

Low-noise gaas MESFET optimization using an orthogonal array approach

This article presents an experimental optimization of the noise figure of small-signal self-aligned FETs. An L₁₈ orthogonal array has been used to find the main effects of specific device parameters on noise performance at 18 GHz. This knowledge has been used to find an alternative device which shows a ～0.7-dB improvement in noise measure without requiring major process changes. Hybrid low-noise amplifiers built with the improved FETs confirm the noise performance and show record power performance for high dynamic range applications. © 1994 John Wiley & Sons, Inc.     

Reactions of the Antiarthritic Drug Aurothiomalate With Phenylmercury(II) Compounds: NMR Studies

Clinical formulations of the antiarthritic drug aurothiomalate sometimes contain phenylmercury(ll) compounds as antimicrobial preservative agents and, in the presence of para-chloromercuri-benzoate, aurothiomalate is a potent inhibitor of collagenase. By (1)H NMR spectroscopy, para-hydroxymercuribenzoate and para-hydroxymercuriphenylsulphonate were shown to react with aurothiomalate by complexing only with the terminal thiomalate of aurothiomalate oligomers, thereby converting them to ring complexes. The reaction was also detected by UV spectroscopy. The arylmercury complexes produced no change in the bulk of the thiomalate residues of aurothiomalate indicating considerable stability of the polymeric structure of aurothiomalate in which each gold is bound to two thiolate residues. The potent inhibition of the mercurial induced collagenase activity may be due either to aurothiomalate or to a complex formed between the terminal thiomalate residues with the arylmercurial. The arylmercury complexes may be unsuitable as antimicrobials in solutions of aurothiomalate because of complexation with the terminal thiomalate residues.     

A universal electromagnetic microactuator using magneticinterconnection concepts

This paper describes a new universal electromagnetic microactuator that makes use of novel magnetic interconnection concepts. In order to realize the universal actuator, planar microinductors are fabricated on a substrate which already contains anisotropically etched Ni/Fe permalloy-electroplated magnetic vias or through-holes. The inductor, which acts as a flux generator, is physically located on one side of the wafer, but is magnetically connected to the opposite side of the wafer where actuation occurs. This approach to actuator design provides for maximum flexibility in the range of applications. In addition, it allows the actuator to be readily connected to driving circuitry without interfering with the actuating device. Multi-layer 3D inductive components are fabricated using a LIGA-like thick photoresist lithography process. The fabricated coils consist of a horseshoe-shaped permalloy-electroplated magnetic core and electroplated copper conductor lines that form the windings around the core. Initial testing using a prototype cantilever beam structure has proven functionality and indicates that the new device has much potential as a low power magnetic microactuator. Many magnetic MEMS applications require an electromagnetic actuator with high efficiency, and some areas which this device is expected to impact include microfluidics, micromotors, optics, and resonating devices     

Effects of acidity,calcium, and aluminium on fish survival and productivity—a review

Fish survival, growth and productivity are dependent on both biological and environmental factors. The latter can be distinguished as edaphic (which includes water quality) and morphometric (which includes lake and stream morphology). Climatic factors are relatively less significant in temperate waters, except over a long time scale, or over wide geographic areas. In the conditions characteristic of acid lakes— low pH, low calcium and high aluminium concentrations—survival may be reduced, growth may be affected and, consequently, productivity will be low. In spite of inconsistencies in the literature, it can be shown that at low pH (? 4.5), a limiting concentration of calcium is about 1 mg litre^?1 and aluminium can have adverse effects at 250 μg litre^?1 within a limited range of pH. These three factors appear to interact. Taking age specific fecundity of adults and survival of eggs and fry, it is possible to predict the limiting conditions for maintenance, growth or decline of a fish population. At pH 4.5 and calcium < 0.8 mg litre^?1 it may be expected that many lakes will be fishless.     

I.r. study of solution-grown crystals of polyethylene: correlation with the model from neutron scattering

The crystal stem arrangement in solution-grown polyethylene crystals has been investigated by the mixed-crystal infra-red technique. Parallel neutron scattering measurements are reported separately. The behaviour of the CD₂ bending vibration is shown to be consistent with a model having 75% adjacent re-entry, 50% dilution of a molecule along the fold plane (110 direction) and a degree of superfolding equivalent to an average molecular weight ($\text{M}\text{?}{}_{\mathrm{w}}$) of 21 000 for each sheet. This is in agreement with results from neutron scattering, which have previously been interpreted using this model. Computer calculations of stem positions based on these parameters are used to calculate the distributions of doublet splittings for several molecular weights. The main features of low-temperature FTi.r. spectra as a function of molecular weight are reproduced in this way.     

Workshop on: Chemistry of Metals in Medicine - The Industrial Perspective

The Workshop was attended by 61 participants from 20 countries. Most of the speakers were industrialists and the Chairpersons and Discussion Leaders were academics.The area "Chemistry of Metals in Medicine" has the potential for producing innovative, high quality, and original research.This is a new and emerging area of biomedical chemistry. Small firms are already being established which are devoted to the new elemental medicine. Major pharmaceutical and healthcare industries too are becoming aware of the major impact which metal chemistry is likely to have on traditional organic pharmacology and of the new opportunities which it presents for advances including the development of metalloenzyme-specific inhibitors, targeted radionuclide complexes for diagnosis and therapy, contrast agents for magnetic resonance imaging, safer mineral and vitamin supplements, new agents for the treatment of neurological, gastrointestinal and cardiovascular disease, skin conditions, cancer, and microbial and viral infections.The European scientific and technological research base in this area is potentially attractive for business. Industrial collaboration and cooperation can be accommodated within the COST framework.     

A model for chain folding in polymer crystals: rough growth faces are consistent with the observed growth rates

The hypothesis that growth surfaces of polymer crystals can be molecularly rough has been tested using models designed to predict lamellar thicknesses and crystal growth rates. Monte Carlo methods used for crystallization of atomic growth units have been adapted to take account of the connectedness along the chains by including two types of restrictions for adding units to the crystal. Firstly new units cannot be added to an established fold surface. Secondly the effect of loops created at the growth surface is simulated by ‘pinning’ points generated at random along the crystalline stem, corresponding to stems growing from chains which are attached elsewhere on the growing face. No interruptions are allowed along crystalline stems. The trends in the results do not depend on the precise nature of the restrictions, and agree with the experimental ones. Crystal thick nesses vary approximately inversely with supercooling at small supercooling, and then level off to an approximately constant ‘plateau’ (no ‘catastrophic’ increase). They are smaller in magnitude than experimental ones since high fold energies are not included. The growth rates obey equations derived for secondary nucleation, though nucleation is certainly not present. The explanation is related to the high free energy (low entropy) states that are required for overall advance of the crystal. The low entropy depends on the crystal thickness as does the high enthalpy states in secondary nucleation. These results resolve the problem that both the existence of lamellae and the growth rate curves were explained on the assumption of molecularly smooth growth surfaces, whereas polymer crystals are often curved.