An Exploration of Helical Asymmetry - Development and Application of Helical Organocatalysts

Within the biochemical world, the helix is of prime importance. This corkscrew shaped three-dimensional structure is found in two biological polymer systems of vast importance: deoxyribonucleic acid (DNA) and many protein structures. DNA consists of two interwoven strands of polynucleotide groups and form what has become known as the double helix . This helical structure is vitally important for the safe keeping and replication of the genetic code for all life, making the shape of the helix uniquely important. Likewise, many proteins (which act as vital biological catalysts which enable so many of the body's chemical reactions to occur) have large sections that consist of a helical structure. As a result, we can appreciate the importance that this helical shape holds in biological chemistry (i.e. within our bodies). The helix also posses another important attribute. The helix is also known to be chiral, that is, it twists in either a right- or left-hended manner. These two handed twists can not be superimposed upon each other, in the same way human hands cannot be laid upon each other.In contrast to nature, mankind has not utilised this exciting design feature when performing synthetic chemistry; not in the body, but in the laboratory. The ability to form chiral molecules (that is right or left handed compounds) selectively is of huge importance, especially in the context of producing new medicines for society. This point is still pertinent as we are still greatly aware of the horrors that the lack of understanding of chiral molecules caused with the use Thalidomide (one handed form of thalidomide was effective for mothers suffering from morning sickness, the other handed form caused the birth defects of children). This helical concept will be married with the use of organic molecules which can act as molecular catalysts (like a very small enzyme) and form compounds in a selective fashion (one hand in preference to another). Often toxic transition metals are used for such purposes which may also be extremely expensive. Organic catalysts offer the chance of effective, clean and cheap formation of complicated compounds which would be of great benefit in forming new medicinal treatments. It is proposed to incorporate the unique properties of the helix when designing my new organic catalysts. As the helix forms either left or right handed corkscrews it is chiral: if the catalyst incorporates a helix, the catalyst will be chiral and can be used to form chiral molecules selectively, producing one handed form of the product over the other (e.g. left handed in preference to right). The special properties of helical compounds (shape, lack of symmetry and crystallinity) make them perfect targets for new organic catalysts. This proposal is exciting as the concept helical organic catalysts have never been investigated before. This research would offer the chance to investigate whether the special nature of the helix in biology translates to mankind's efforts to make molecules as efficient and selectively as nature can. Can the special feature of the helix in biology work in synthetic chemistry as practised by mankind? If successful, it is envisaged we will be able to synthesise new and complicated amino acids from very inexpensive malonic acid compounds. Such amino acids may be of use in designing new small proteins with potential use in medicine. The benefits to synthetic chemistry could be large. New methods for forming chiral compounds are always required, especially if they are effective and cheap. This may have significant benefits for the pharmaceutical industry in this country and potentially, for medicines in the future.