Seeing bonds

Peering at molecular structures is what chemists do. Technology that can improve the way that they see this world can have a huge impact on the field. In one such leap, researchers in China report the first visualisation of a hydrogen bond using atomic force microscopy (AFM).

First pictures of hydrogen bonds unveiledChemistry World, 26 September 2013.

Image credit: Xiaohui Qiu

Precision strike

In the last 100 years antibiotics have saved millions of lives. However, they are indiscriminate weapons: they kill useful bacteria, such as those in the human gut which extract nutrients, as efficiently as they kill the nasty disease-causing sort. Ben Feringa, of the University of Groningen, in the Netherlands, and his colleagues have devised a method to make antibiotics more selective.

As they report in Nature Chemistry, this was achieved by slapping chemical structures called diazo compounds to a class of antibiotic called quinolones, developed to treat urinary tract infections. Different diazo compounds absorb particular wavelengths of light (it is these structures which give dyes their distinctive colour). They then added the mixture to a Petri dish containing the bacterium E. coli, shielded part of the dish and irradiated the uncovered parts with ultraviolet light. Two of the nine compounds they tested worked as hoped: whereas E. coli remained abundant in the covered parts of the Petri dish, the sections exposed to the light were almost entirely cleared of bacteria.

Crucially, in the half hour or so after exposure to the light, the diazo groups lose energy and revert to their original structure. This, in turn, switches the antibiotic off again. That way, when the antibiotic travels to other parts of the body or is excreted, it does so in its inactive form, and thus remains harmless to the friendly bacteria living in the gut. (And beyond: excreted antibiotics that make their way into sewers have been blamed for spurring the development of drug-resistant bacteria in the wild.)

The brief active window does, however, mean that Dr Feringa’s drug would only be useful in fighting localised infections, where a half-hour antibiotic raid is plenty, rather than more general ones which require a sustained onslaught. And though light can, in principle, be delivered deep inside the body using an endoscope (as happens in some cancer treatments), this is finicky and expensive in practice. As a result, light-activated antibiotics would probably be limited to easily accessible infections on the skin (in wounds, for instance) or in the mouth, ears or nose.

At least for now, that is, for Dr Feringa is working on flipping his chemical switch using sources of energy found inside the body, such as heat or certain energy-rich enzymes. If he succeeds, incidents of antibiotic friendly fire may be consigned to the history of antibacterial warfare.

First published on

Image credit: Ben Feringa

Organocatalysis: A new era in chemical synthesis

Some time ago Oxford was host to a brilliant chemist, Prof. D.W.C. MacMillan of Princeton University. He delivered the Vertex Lecture at the Department of Chemistry speaking on ‘New concepts in Catalysis’. His research interests are in the area of Organocatalysis, or the use of small organic molecules to catalyze organic transformations, a new immerging field in enantioselective molecule synthesis. Simply put, it is the use of environmentally friendly and easily available chemicals to carry out reactions at normal conditions of room temperature and atmospheric pressure to create chemical bonds at a specific position and in a specific direction.

What is more special about this field apart from its scientific value and environmental friendliness is that in the period of 1998 to 2008 more than 1500 manuscripts described use of organocatalysis in more than 150 discrete reaction types. A remarkable number given that there were no reports of such catalysis in the year 1995 and on an average chemistry produces only a handful of new reaction types a decade. This field has taken the synthesis community by a storm.

It is interesting to look at these facts as they provide insight into how scientific communities can bypass an important research area for decades and then suddenly embrace it with fervent enthusiasm. MacMillan says in an essay in Nature, “It is hard to answer why a field was overlooked for so long. One perspective is that it is impossible to overlook a field that does not yet exist which is similar to the thought that scientists cannot work on a problem they haven’t found.”

And why was there such rapid growth in research in this area? Primarily, the field offered real advantages to researchers and industry and at an easy and low cost of carrying out such reactions in laboratory. Reactions were being discovered everyday which were able to replace use of organometallic systems which are expensive, toxic and sensitive to air or moisture. Organic molecules are generally insensitive to air or moisture, small chiral molecules can be derived from nature, thus are readily accessible and cheap to prepare, the by-products are non-toxic and environmental friendly. It is also widely recognized that during large scale production of chemicals the removal of toxic catalyst-related impurities from the waste stream can often have a large financial impact. All these factors led to rapid growth and increased competition in the area of organocatalysis, which in turn accelerated the pace of innovation and discovery.

Apart from MacMillan’s large contribution to the field in terms of new chemistry, there is one contribution which he particularly boasts of and that is, naming this field: Organocatalysis. So, what’s in a name? He answers, “Consider the success of the terms nanotechnology at globally shifting the visibility and perception of areas of research. Organocatalysis provided a strong identity and helped unify a fledgling field by attracting attention of the broader chemical synthesis community.” These reactions are similar in mechanism to the ones catalysed by enzymes, which are much more complex molecules than the one used under the term organocatalysis. These discoveries and innovations have brought chemists one step closer to be able to outwit nature. Very rarely in the history of science does a whole new field emerge that not only has the potential to change the way things are done today but also the ability to grow so quickly.

Reference: MacMillan, D. (2008). The advent and development of organocatalysis Nature, 455(7211), 304-308 DOI: 10.1038/nature07367

Further reading: ReviewReactionsNature Insight