DIVISION OF CHEMICAL EDUCATION

235th ACS National Meeting

New Orleans, LA

April 6-10, 2008

TUESDAY AFTERNOON

Chemical Evolution from Origins of Life to Modern Society

Evolutionary Ideas and Applications

Cosponsored by ENVR, GEOC, and ORGN
S. R. Seidel, J. M. Friedrich, and L. Zaikowski, Organizers, Presiding

1:30 — Introductory Remarks.

1:35 —1495. The evolution of chemistry through synthesis (and of synthesis in chemistry). T. R. Hoye

2:05 —1496. Molecular machines; Natural and artificial molecular motors. T. W. Bell

2:35 —1497. Gene expression: Control with designed molecules. B. Olenyuk

3:05 — Intermission.

3:20 —1498. Natural product structural diversity, biosynthesis, and drug discovery. B. Shen

3:50 —1499. Combinatorial chemistry and diversity-oriented synthesis. A. W. Czarnik

4:20 —1500. Rapid evolution caused by human-induced environmental changes. S. R. Palumbi

4:50 — Concluding Remarks.

ABSTRACTS

CHED 1495

The evolution of chemistry through synthesis (and of synthesis in chemistry)

Thomas R. Hoye, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, Fax: 612-626-7541

Other than human activities over the last ~two centuries, from the beginning of life the synthesis/creation of new molecules has taken place essentially exclusively in the domain of biology—and at the whim of evolution. Human intervention dramatically altered that natural course. Synthesis chemists, from alchemists to those engaged in state-of-the-art developments in the field, have used their higher order skills in a strive to push the limits of how and what we construct as new molecular entities. In this lecture I will attempt to offer some perspective on aspects of that evolution. Synthesis of products of nature—carbon-containing compounds that comprise the natural world of organic chemistry—will be emphasized. Likely topics are the underpinnings of structural theories, roles of mechanistic thinking (curly arrows and computers) and technological developments (chromatography and spectroscopies), the age of catalysis (organometallics and more), strategy and logic (retrosynthetic analysis), the world(s) of asymmetry, green chemistries, and innovations (how) vs. targets (what).

CHED 1496

Molecular machines; Natural and artificial molecular motors

Thomas W. Bell, Department of Chemistry, University of Nevada, Reno, NV 89557-0216, Fax: 775-784-6804, twb@unr.edu

Biological molecular motors, such as F1-ATPase, have inspired chemists to devise artificial analogs of potential use in nanotechnology. This presentation briefly reviews the major types of natural and artificial molecular motors, then presents the author's own approach to molecular motors based on photoisomerization of substituted 9-(2,2,2-triphenylethylidene)fluorenes. Quantum yields for photoisomerization of the 2-tert-butyl derivative at various wavelengths are significant, ranging from 4 9% (J.W. Barr, T.W. Bell, V.J. Catalano, J.I. Cline, D.J. Phillips, R. Procupez, J. Phys. Chem. 2005, A109, 11650-11654), despite theoretical prediction of inefficient or negligible isomerization of the parent hydrocarbon, fulvene. We have also synthesized several analogs with polar substituents, which increase absorption wavelengths and can greatly enhance photoisomerization quantum yields in this system. The current status of our efforts to synthesize the target molecular motor, containing a chiral triarylmethane moiety, is also described.

CHED 1497

Gene expression: Control with designed molecules

Bogdan Olenyuk, Department of Chemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ 85721, Fax: 520-621-8407, olenyuk@email.arizona.edu

The fundamental role of gene expression and the recognition of transcription factors and co-activators as important control elements of cell growth, differentiation, and apoptosis created an ever-increasing interest for these proteins as potential targets for therapeutic intervention in human diseases. The vast array of information available for their molecular structure and mode of action in various biological contexts, combined with the new opportunities offered by the technologies of structure-based design, functional genomics and proteomics are creating an exciting opportunity for the discovery of a new generation of highly selective small molecules for regulation of gene expression. By combining chemical synthesis with the methods of molecular biology and genetics, new strategies of modulating transcription are being developed. This lecture will cover several fundamental aspects of transcription factor-based gene regulation and provide an example of targeting transcription factor-coactivator interactions by exploiting the tissue-specific and gene-specific differences in transcriptional machinery composition.

CHED 1498

Natural product structural diversity, biosynthesis, and drug discovery

Ben Shen, Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI 53705, Fax: 608-262-7582, bshen@pharmacy.wisc.edu

Natural products represent a vast structural diversity not matched by any other sources of small molecules, and natural products remain the best source and inspiration of new drug discovery and development. In spite of the huge molecular space natural products cover, the biosynthetic machinery for natural products is remarkably conserved. Recent advances in understanding the genetics, biochemistry, and chemistry of natural product biosynthetic pathways are shedding new insights into how these relatively conserved pathways are evolved to account for the myriad of structural diversity seen with natural products. It is now also possible to engineer natural product biosynthetic machinery to make “designer” natural products and exploit genetic signatures of biosynthetic machinery to search for “yet-to-be-discovered” natural products. Examples from our current studies on polyketide and peptide natural product biosynthesis and engineering will be presented to highlight the progress in this field.

CHED 1499

Combinatorial chemistry and diversity-oriented synthesis

Anthony W. Czarnik, Department of Chemistry, University of Nevada, Reno, Reno, NV 89557, Fax: 775-853-1124, aczarnik@unr.edu

The process of biological evolution requires the generation of a wide diversity of new biomolecules, which then afford an organism either a competitive disadvantage (most often) or a competitive advantage (occasionally). That diversity of molecules is created by the process of random mutation.

In Chemistry, we likewise desire to discover new substances whose properties yield a competitive advantage, but in the commercial or intellectual marketplaces. The combinatorial approach has yielded a new paradigm for discovering such substances- make many things with diverse structures using synthesis techniques that are efficient and, ideally, also facilitate the high-throughput evaluation of their properties.

Chemical 'mutation' cannot be random; there are too many conceivable substances for anyone to make them all. Instead, chemists apply both existing knowledge and computational means to direct their decisions of what 'chemical libraries' to make. This approach, which began using libraries of biopolymers, has been expanded over the past 15 years to the preparation and screening of libraries useful in virtually all areas of chemical discovery.

CHED 1500

Rapid evolution caused by human-induced environmental changes

Stephen R. Palumbi, Hopkins Marine Station, Stanford University, Pacific Grove, CA 93950, spalumbi@stanford.edu

Evolution of populations within species is driven by natural selection, genetic drift and mutation pressure. Favoring rapid evolution are big population sizes, short generation times, and strong natural selection. Human change of the biosphere results in strong selection pressure because ecosystem properties have been so seriously altered. For species with big population sizes and short generation times, rapid evolution is often the result such as in many microbial disease organisms, small insects, common fisheries species and annual plants. Species with small populations or long generation times tend not to respond to human change evolutionarily but instead exhibit rapid declines in population numbers: such species are most likely to be listed as endangered or extinct. Human action can also affect speciation rates. The most rapid speciation occurs when disruptive selection occurs across a landscape where movement is curtailed. When humans create a fragmented landscape across an environmental mosaic, rapid divergence and reproductive isolation can result. Rapid evolution due to human environmental change is not just an intellectual curiosity. It generates huge costs in medical care and in agricultural losses. It may also increase the rate of evolution of highly virulent diseases or particularly noxious weeds.