The Challenge:
Molecules are collections of atoms connected together in a specific way. Even constrained to those elements most used (C, N, H, O, P, S) the number of possible molecules, even using small numbers of atoms, is vast – AND every molecule has different properties. It is unsurprising then that much of modern life (and life itself) is based on molecules with specific structures and properties (e.g. as pharmaceuticals, agrochemicals, plastics, liquid crystals).
The task of making molecules is challenging – an organic molecule containing just a few dozen atoms (e.g. taxol) can easily take many man-years of effort to complete. The result is that many of the molecules we use are compromises – the easiest to make with acceptable function, rather than being the best for the job. One example of this is in pharmaceuticals when the need to use simple, easy to make compounds leads to cross-activity (interaction with other than the target biological system) as the compromise, and hence undesirable side effects.
The aim of the Dial-a-Molecule Grand Challenge Network is to make the synthesis of any desired molecule as easy as dialing a number thus greatly empowering researchers, and removing a severe constraint to progress, in many fields. A linked aim is to move towards 100% efficient synthesis. Currently in the production of a molecule many times the mass of the desired product (typically 1000s of times) is produced as waste with consequent disposal and cost implications. With 100% efficient synthesis there would be no waste to dispose of and the process would be much cheaper as well as consuming less energy.
Why Grand Challenge?
The importance and difficulty of the challenge can be appreciated by comparison with oligonucleotide synthesis. Automated oligonucleotide synthesis has had a transformative impact on molecular biology and enabled the human genome project. Consider the potential impact of a similar level of efficiency and predictability applied to any desired class of synthetic molecules. It would revolutionise problem solving across diverse disciplines such as biology, pharmaceuticals/agrochemicals, effect chemicals, molecular materials, nanomaterials etc. The scale of the Grand Challenge becomes clear, however, when one considers that oligonucleotide synthesis:
- involves only three basic types of chemistry
- is carried out on a very narrow and functionally similar set of building blocks
- though extremely high yielding, is massively inefficient in terms of waste and atom economy
- required 20 years of effort to reach this level of sophistication
Therefore to be able to make any complex molecular system, with the additional focus on economics / efficiency / sustainability, is going to require a step-change in approach.
It will take contributions from many areas of science, engineering and mathematics, to tackle the Grand Challenge. Although Dial-a-Molecule is expected to take 20-40 years to achieve, there will be substantial advances, and consequent commercial benefits, even in the initial stages.
Significance:
It cannot be stressed enough that the impact of addressing the Grand Challenge will be vast. Synthesis of molecules is both a central driver for, and a serious constraint in a myriad of research disciplines, associated industries and other grand challenges. For example, a recent pan-industry report on synthetic chemistry in the healthcare environment stated, when synthetic enablement is lacking, we see projects stall, even those with the best biological or clinical rationale. Emerging challenges in fields such as (nano)materials, chemical biology and next-generation healthcare pose synthetic problems that are beyond the scope of existing technologies.
Examples for such new challenges are:
- expansion of accessible chemical space to facilitate highly specific small molecule interactions with any genomic protein (chemical genomics/pharmaceuticals); next-generation biological drugs (integrated synthetic chemistry and synthetic biology)
- molecular electronics (e.g. for spintronics applications)
- non-invasive monitoring tools (markers, imaging agents)
- security-related products (smart-dyes, etc.)
- components of smart materials
