Structural chemistry future directions

The structural information developed in this project and molecular modeling studies based thereon proved to be very valuable in guiding the medicinal chemistry effort directed toward the development of therapeutically useful cathepsin K inhibitors, as will be discussed here. Through this work it has also been possible to highlight some of the present limitations on the use of structural information, the recognition of which can serve to guide the advances necessary to make it even more productive in the future. 

The chapter consists of nine sections. Sections II through VII deal with the pterin-containing molybdenum enzymes. Biochemical and model studies of molybdopterin, Mo-co, and related species are described in Section II. In Section III, we briefly survey physical and spectroscopic techniques employed in the study of the enzymes, and consider their impact upon the current understanding of the coordination about the molybdenum atom in sulfite oxidase and xanthine oxidase. Model studies are described in Sections IV and V. Section IV concentrates on structural and spectroscopic models, whereas Section V considers aspects of the reactivity of model and enzyme systems. The xanthine oxidase cycle (Section VI) and facets of intramolecular electron transfer in molybdenum enzymes (Section VII) are then treated. Section VIII describes the pterin-containing tungsten enzymes and the evolving model chemistry thereof Future directions are addressed in Section IX. 

Crystalline and amorphous silicons, which are currently investigated in the field of solid-state physics, are still considered as unrelated to polysilanes and related macromolecules, which are studied in the field of organosilicon chemistry. A new idea proposed in this chapter is that these materials are related and can be understood in terms of the dimensional hierarchy of silicon-backbone materials. The electronic structures of one-dimensional polymers (polysilanes) are discussed. The effects of side groups and conformations were calculated theoretically and are discussed in the light of such experimental data as UV absorption, photoluminescence, and UV photospectroscopy (UPS) measurements. Finally, future directions in the development of silicon-based polymers are indicated on the basis of some novel efforts to extend silicon-based polymers to high-dimensional polymers, one-dimensional superlattices, and metallic polymers with alternating double bonds. 

Synthetic methods have been developed to prepare twisted polyarenes with diverse structural features. A large number of X-ray structures have been reported, allowing direct measurements of the extent of distortion from planarity. However, the use of these twisted compounds for synthetic applications remains underdeveloped. While limited success has been achieved in using optically active twisted polyarenes as catalysts for asymmetric induction, a systematic study of this potentially fruitful area has not been undertaken. Molecular recognition is another area that is still in its infancy. Optical and electronic properties have not been exploited. However, there is no reason to believe that the chemistry of twisted polyarenes will not be as fruitful in the future as has been observed over the past 70 years. Because the future direction of the development of this fascinating class of compounds can barely be imagined, success can come from a wide variety of areas. 

One future direction likely to be pursued with vigor is the marriage of de novo design methodologies with ideas and practices from the burgeoning field of combinatorial chemistry. -- Combining the focus (rf structural constraints and the rapidity of structure generation with the inherent accessibility of combinatorial synthetic routes is almost certain to be fruitful. 

Williams, M., Franklin, G. Future Directions in Integrated Information Systems Is there a Strategic Advantage . In Chemical Structures The International Language of Chemistry, Warr, W.A., Ed. Springer-Verlag Berlin, 1988 pp.11-21. 

At the same time we have illustrated with examples of clusters that the theoretical approaches involving the coupling between electronic structure and motion of nuclei are useful tools removing the border between quantum chemistry and molecular dynamics. The development of new methods allowing the study of time-dependent phenomena involving electronic excitation and motion of nuclei might become an attractive future direction of computational chemistry. 

Interpreting these results on a detailed molecular basis is difficult because we have at present no direct structural data proving the nature of the split Co(IIl/lI) voltammetry (which seems critical to the electrocatalytic efficacy). Experiments on the dissolved monomeric porphyrin, in CH-C solvent, reveal a strong tendency for association, especially for the tetra(o-aminophenyl)porphyrin. From this observation, we have speculated (3) that the split Co(III/II) wave may represent reactivity of non-associated (dimer ) and associated forms of the cobalt tetra(o-aminophenyl)porphyrins, and that these states play different roles in the dioxygen reduction chemistry. That dimeric cobalt porphyrins in particular can yield more efficient four electron dioxygen reduction pathways is well known (24). Our results suggest that efforts to incorporate more structurally well defined dimeric porphyrins into polymer films may be a worthwhile line of future research. 

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