Henry Rzepa, talks and Presentations

A history of symmetry, stereochemistry and how the Woodward-Hoffman rules for pericyclic reactions came about.

The future of the chemistry textbook, and how disruptive technologies and social media might impact upon it. The talk is available at http://www.ch.ic.ac.uk/rzepa/talks/imperial13/

Changing ways of sharing research in Chemistry In 1994 onwards, the Internet was seen as having an increasingly influential potential for how chemistry may be handled, shared, stored and communicated, and how the Internet might have impacted upon the quality, reproducibility and re-use of both experimental observation and computational modelling for new scientific opportunities. Examples will be presented to illustrate from a personal viewpoint how the author carried out collaborative research in pre-Internet days, and how things have changed up to 2012. This will include a review of early attempts at electronic conferencing, examples of modern "datuments" as data-enriched interactive articles, the role of digital repositories and how environments such as blogs and Wikis can be used to promote collaborative new science.

The first part of the talk will cover the essential features of modern chiroptical spectroscopies, and the second will illustrate these with several case studies. These will include the rather controversial histories of the determination of the absolute configurations of an important series of sulfur-containing natural products such as the dethiochaetocins and dehydrogliotoxins. The mechanism of dethionation of these species has been claimed to involve both retention and inversion of configuration at the carbon-S centre, and a possible route for either process is shown in the scheme below. Computational chemistry is also used to chart the viability of such a mechanism, although the techniques used to do so require methods that have only recently been introduced as routine procedures. The take-home message is intended to illustrate that the use of computational modeling for both chiroptical spectroscopy and associated mechanistic exploration is increasingly regarded as a sine qua non of the synthetic laboratory.

Of the 61M known compounds, it is estimated only around 1M have been reported as scalemic, a term used to describe any non-racemic chiral compound. Of these, an unknown proportion have a clearly established absolute configuration for the dominant enantiomer. Absolute configurations can be established by anomalous dispersion X-ray crystallography (and it is estimated about 11,000 such determinations have been made) or chiroptical spectroscopies. This talk concentrates on the latter, and in particular illustrates how electronic circular dichroism, optical rotatory power, optical rotatory dispersion and vibrational circular dichroism, coupled with powerful modern quantum mechanical simulations, can be used to assign the absolute configurations of scalemic molecules. In effect, the QM "chiroptical instrument" is seen as an indespensible symbiotic component of a modern synthetic laboratory, and the skills needed to operate it properly should be part of the training of any aspiring synthetic chemist who may be making scalemic molecules.

I venture to suggest that ... the general development of the human race to be well and effectually completed when all men, in all places, without any loss of time, at a low rate of charge, are cognizant through their senses, of all that they desire to be cognizant of in all other places. ... This is the grand annihilation of time and place which we are all striving for, and which in one small part we have been permitted to see actually realised" (Samuel Butler, 1863, [1])

The concept of a modern scientific journal becomes 346 years old in 2011 (DOI: 10.1098/rstl.1665.0001), although only since 1994 has the journal article been embedded in the Internet and Web era (DOI: 10.1039/C39940001907). Although the structure of the article itself morphed little during the first part of the Internet age, there are now signs that many aspects of its creation and dissemination are starting to evolve more rapidly. Here, several potential future enhancements are reviewed, including the role of the scientific blog in augmenting the effectiveness of the peer-review processes, the role of data-integrity within the article, integration of Web-enhanced and other data-rich and functional objects, the role of open digital repositories, article semantification, and delivery and re-functionalisation of the re-invented article via new generations of mobile personal devices.

The iPad is the first of an apparently new generation of personal information appliance. The app has become the new shrink-wrapped access point for the web of chemistry, and the metaphors are driven by touch and the sensors built into the devices. Whilst it would be fair to say these have not really started being explored by chemists, we have had one year to explore the potential. Some low-hanging fruits can be picked, including redesigning the text book, the lecture and the laboratory for this medium. But will the concept merely fragment and dumb-down chemistry in yet another proprietory manner, or could this be the start of the next revolution?

A reflection on aspects of scientific publishing, journals and other forms of discourse, based on two scientific stories.

There is now increasing focus on the imortance of structured data as an integral part of the primary scientific, technical and medical publication processes. Whereas traditional journals version 1 (circa 1680-2008) have rarely given structured and semantically enabled data much prominence (this not enhancing their business model), there is now far more pressure (from eg funding councils) to ensure that the often considerable investments in securing the data are not lost to the community, or to posterity. This presentation will give a brief demonstration of how the (computational) data generating resource (the HPC unit at Imperial College) has been structured and preserved via a uportal developed within the HPC unit, ingested into a digital repository, and now embedded in primary journal articles (version 2) and taught courses in the chemistry department.

Scientific ideas can take a long time to gestate, and their fusion sometimes emerges from the most unexpected of directions. The talk will illustrate a chemist’s attempt to merge ideas from different areas of mathematics, molecular biology, physics and indeed chemistry, and which together span some 314 years of scientific (and indeed musical) development. The central theme concerns twisted objects known as Mobius bands, their molecular analogues, and the consequences of exploring what happens when additional twists are added. The talk will also address the theme of how to express the emerging three dimensional concepts in a visually comprehensible and semantically harvestable manner suitable for both a (re-invention) of the scientific journal for an Internet era, and in presentations to an audience, with the help of some scissors, paper and hopefully the audience itself.

Professor Henry Rzepa has had research interests in both computational chemistry and chemical information for thirty years, and was a pioneer of implementing chemistry on the Web at its start in 1993. He is the author of around 250 scientific articles in the former and 50 in the latter category. The talk today will be a fusion of these interests, and in particular how modern informatics practices can suubstantially enhance the scientific perception of published articles, taking the "paper" well beyond its old cellulose based limits.

Both chirality and aromaticity are cornerstone concepts for organic chemistry. Both had their origins in the 1840s or thereafter in the work of Pasteur, van't Hoff and LeBel for the former and Faraday, Loschmidt, Kekule, Armstrong for the latter, this reaching its first stage of theoretical maturity with Huckel's quantum mechanical analysis in the 20th Century (the famous 4n+2 rule). For a long period, these two concepts were thought to be exclusive; after all aromaticity manifested almost entirely in flat (achiral) benzenoid rings! Another concept, topology, also originated in the 1840s, having been coined by the mathematician Johann Listing, who also proposed fascinating topological objects such as trefoil knots, and rings now better known by their co-discoverer, Mobius. In the 1960s, the concepts of Mobius topologies and aromaticity started merging. The chemist Heilbronner proposed aromaticity rules for Mobius cycles, although he did not identify such cycles as being chiral (this property appears to have been gradually realised only years later, although its difficult to find this expressed in print). The first such Mobius molecule was only synthesized in 2003; it was not however particularly aromatic! Meanwhile, in 1978 molecular biologists had discovered the fascinating twists and knots in cyclic DNA, via James Wang's topoisomerase enzymes. This was expressed using a concept known as supercoiling, and a new generation of mathematicians formalised this into an equation expressing a so-called linking number, which is comprised of twist and writhe; Lk = T + W ...(1) Applied extensively to the properties of cyclic DNA, these concepts did not migrate at all to organic chemists, who by and large dealt with much smaller molecules. Listing in 1847 had also introduced the concept of paradromic winding, which in modern language maps to imparting further twists to the basic Mobius topology. In 2005, we fused these various concepts from chemistry, topology and molecular biology, recognising that a new form of aromaticity based on double- and higher twisted conjugated, and importantly chiral, rings could be possible. We identified various interesting candidate molecules, but were surprised by how relatively stable they appeared (by computation), given they were at least twice as twisted as the classical Mobius rings. We found a resolution to this paradox in equation (1). The (quantum mechanical) instability we realised is associated with T and not with W. We have now computed values of T and W for a range of topologically interesting (and chiral!) systems, and approximately, those that appear the most synthetically interesting have large values of W compared to T. So W (the writhe) can be regarded as a fundamentally new property of cyclic conjugated molecules, and one moreover that might be associated with stability. This has led to our proposal that eqn (1) and the Huckel 4n+2 rule can be combined as follows; If Lk is even (measured in units of π), aromaticity is implied for 4n+2 cyclic conjugated electrons If Lk is odd, aromaticity is implied for 4n cyclic conjugated electrons Intriguingly both T and W are chiral indices, and they can act together or oppose to create some fascinating novel chiral isomerisms. In a general sense, this type of aromaticity is chiral, and benzene like systems are very much the achiral exceptions (having Lk = 0). At the end of the talk, I will speculate on some potential real world applications of this fascinating new form of chiral aromaticity, particularly to the design of new chiral metal ligands, and perhaps even mention another interest of ours, the Semantic Web, and how this might in the future enable more efficient fusion of diverse ideas and concepts (linking is a fundamental concept there as well!).

The Semantic wiki as a model for an intelligent chemistry journal, where a case is made for investigating Wikis as an authoring tool for the scientific publication process.

A presentation given at the 233rd ACS Meeting in Chicago, as part of the session on using social networking tools to teach chemistry, and on the theme of Wikipedia - a holistic model for the communal creation of chemical course content

An exploration of unexpected links between different subjects in chemistry, and how new insights into chiral aromaticity came to be revealed.