Optimisation and Scale Up of EXACTYMER

Nature uses biopolymers with defined sequences to transmit vital information, through DNA and RNA, which in turn fabricates unique 3-D structures in the form of peptides and proteins. If practical synthesis of similarly defined monomer sequence synthetic polymers that can mimic nature's accuracy, size and complexity, a whole wide range of opportunities and possibilities would be revealed. From the delivery of medicines (Hartmann & Börner, 2009) to the fabrication of complex materials (Lutz, et al., 2016) to molecular information storage (Lutz, 2015), a new paradigm shift will occur if this synthetic pathway is established.
The production of synthetic polymers with precisely defined monomer sequences have been attempted through various process, such as ionic polymerisation, controlled radical polymerisations such as atom radical transfer process (ARTP), and ring-opening metathesis (Srichan, et al., 2014). But as quoted, "owing to the statistical nature or chain growth co-polymerisation, chain to chain sequence inhomogeneity is still present in these polymers". Overall, to achieve complete control over monomer sequences with low error rates, a two-step procedure is required. Firstly, a building block is added to the growing chain terminus, to which, secondly, a new reactive chain terminus is generated, by removing a temporary protecting group or transforming passive functionality into reactive functional ends. It is imperative that each step is 100% selective and complete, no side reactions and no sequence deletion errors. This is, in total, referred to as iterative synthesis. Currently accurate purification and eventual scale-up are barriers to the wide-scale uptake of this technology.
To date, a great majority of sequence-defined polymers have been developed through solid phase platforms, with the principal advantage of this technology, allowing for simple removal of reaction debris and excess monomer through washing with solvent. However, many limitations, from the support capping the concentration of the growing oligomer, to slow reaction rates due to reagent diffusion into the solid support, as well chemical and thermal instability of the support for many of the novel chemistries required for synthetic sequence-defined polymers, leaves a more robust process to be desired. Liquid phase systems, on the contrary, do not suffer from these drawbacks, but has not been widely used due to the lack of a general separation methodology.
The ambition of the EXACTYMER project looks to utilised liquid phase systems to create new super-stable, ultra-selective nanomembranes with high permeances, that ultimately will allow for rapid, repeated purifications in exactymer fabrication and integration into other ISPPPS technologies. With automation and in-line analysis, a breakthrough platform will be creating providing access to a new range of exact monomer sequences (exactymers) which will have transformative impacts on molecular healthcare, nanotechnology and information storage. Building off the established HOMOSTAR nanofiltration platform developed within the Livingston group and other OSN technologies (Székely, et al., 2014), the success of this project will place Europe in a world leading position in this emerging field.