Volume 74, Issue 5

The future of medicinal chemistry as both a pure and an applied science has been considered relative to trends that are already having a significant impact upon drug discovery and development. After quickly reviewing how medicinal chemistry has been practiced to date, topics considered into the future include: pursuing therapeutic efficacy, addressing 3D structure within database settings, assuring absorption, directing distribution, controlling metabolism, optimizing elimination, and avoiding toxicity. It is suggested that as the exploration of these topics proceeds into the new millennium by deploying combinatorial chemistry coupled to high-throughput screening, medicinal chemistry will play a key role as a central interpreter of the underlying structure­activity relationships such that the overall process of drug discovery and development will be knowledge-generating. As fundamental knowledge accumulates across all of these areas, virtual approaches will eventually become firmly anchored to experimental and theoretical databases having validated clinical predictability. The potential impact of some of the recent trends in process chemistry, and in analytical chemistry using X-ray diffraction as an exemplary method, are additionally highlighted before reiterating the article's major points in a summary section. From this purview, the summary also considers the education of future medicinal chemists, notes potential issues related to the future of pharmaceutical-related intellectual property, and concludes by alluding to a brewing paradox between enhanced knowledge and enhanced molecular diversity relative to the future discovery of new drugs.

A procedure is proposed to name new elements. After the discovery of a new element is established by a joint IUPAC­IUPAP Working Group, the discoverers are invited to propose a name and a symbol to the IUPAC Inorganic Chemistry Division. Elements can be named after a mythological concept, a mineral, a place or country, a property, or a scientist. After examination and acceptance by the Inorganic Chemistry Division, the proposal follows the accepted IUPAC procedure and is then submitted to the IUPAC Council for approval.

Over the past two decades, the term "heavy metals" has been widely used. It is often used as a group name for metals and semimetals (metalloids) that have been associated with contamination and potential toxicity or ecotoxicity. At the same time, legal regulations often specify a list of "heavy metals" to which they apply. Such lists differ from one set of regulations to another and the term is sometimes used without even specifying which "heavy metals" are covered. However, there is no authoritative definition to be found in the relevant literature. There is a tendency, unsupported by the facts, to assume that all so-called "heavy metals" and their compounds have highly toxic or ecotoxic properties. This has no basis in chemical or toxicological data. Thus, the term "heavy metals" is both meaningless and misleading. Even the term "metal" is commonly misused in both toxicological literature and in legislation to mean the pure metal and all the chemical species in which it may exist. This usage implies that the pure metal and all its compounds have the same physicochemical, biological, and toxicological properties, which is untrue. In order to avoid the use of the term "heavy metal", a new classification based on the periodic table is needed. Such a classification should reflect our understanding of the chemical basis of toxicity and allow toxic effects to be predicted.

Cyclophane and linear phane systems are considered as parent hydrides. Their derivatives are named in conformity with the principles, rules, and conventions prescribed for naming organic compounds. The following nomenclatural features are described: indicated and added hydrogen, order of seniority for numbering, substituents expressed as suffixes, substituents cited as prefixes, phane parent hydrides modified by addition or subtraction of hydrogen atoms, and polyfunctional derivatives.

Method validation is one of the measures universally recognized as a necessary part of a comprehensive system of quality assurance in analytical chemistry. In the past, ISO, IUPAC, and AOAC International have cooperated to produce agreed protocols or guidelines on the "Design, conduct and interpretation of method performance studies" [1], on the "Proficiency testing of (chemical) analytical laboratories" [2], on "Internal quality control in analytical chemistry laboratories" [3], and on "The use of recovery information in analytical measurement" [4]. The Working Group that produced these protocols/guidelines has now been mandated by IUPAC to prepare guidelines on the single-laboratory validation of methods of analysis. These guidelines provide minimum recommendations on procedures that should be employed to ensure adequate validation of analytical methods. A draft of the guidelines has been discussed at an International Symposium on the Harmonization of Quality Assurance Systems in Chemical Laboratory, the proceedings from which have been published by the UK Royal Society of Chemistry.

Eight persons from five institutions in different countries carried out polymerizations of aniline following the same preparation protocol. In a "standard" procedure, aniline hydrochloride was oxidized with ammonium peroxydisulfate in aqueous medium at ambient temperature. The yield of polyaniline was higher than 90 % in all cases. The electrical conductivity of polyaniline hydrochloride thus prepared was 4.4 ± 1.7 S cm -1 (average of 59 samples), measured at room temperature. A product with defined electrical properties could be obtained in various laboratories by following the same synthetic procedure. The influence of reduced reaction temperature and increased acidity of the polymerization medium on polyaniline conductivity were also addressed. The conductivity changes occurring during the storage of polyaniline were monitored. The density of polyaniline hydrochloride was 1.329 g cm -3 . The average conductivity of corresponding polyaniline bases was 1.4 x10­8 S cm -1 , the density being 1.245 g cm -1 . Additional changes in the conductivity take place during storage. Aging is more pronounced in powders than in compressed samples. As far as aging effects are concerned, their assessment is relative. The observed reduction in the conductivity by ~10 % after more than one-year storage is large but, compared with the low conductivity of corresponding polyaniline (PANI) base, such a change is negligible. For most applications, an acceptable level of conductivity may be maintained throughout the expected lifetime.

Poly(hexano-6-lactone) (PCL*) fibers were enzymatically degraded by a hydrolase in vitro. The extent of degradation of PCL fibers was examined by weight loss, mechanical properties loss such as tensile strength and ultimate elongation decreases, and visual observations by scanning electron microscopy. The in vitro degradation of PCL fibers was carried out using a lipoprotein lipase (Lipase-PS) as a hydrolase. The kinetic study on the weight loss of PCL fiber accompanying the enzymatic degradation suggested that the degradation of PCL fibers gradually takes place from the surface, not bulk degradation. The rate of degradation was found to depend on draw ratio and crystallinity of the PCL fibers. The strength loss of PCL fibers in the course of degradation took place faster than the weight loss of PCL fibers. Sonic velocity measurements as well as dynamic mechanical properties of PCL fibers were also examined as a function of weight loss of sample fibers with Lipase-PS treatments. It was shown that sonic velocity and value of loss tangent d changed steeply for undrawn PCL fiber in the first step with enzymatic digestion.