Synthesis of Sequence-Defined and Sequence-Controlled Polyphosphodiesters and Their Self-Assembly

Having control over the sequence is the ultimate key to achieve the high degree structural control over polymeric materials. The ability to control the sequence of building blocks in polymer leads to precise, well-managed synthetic macromolecules with unique and ordered chemical and physical properties. Synthetic macromolecules have entered almost every aspect of modern life, but the use of sequence (as is so potent in biology) has not yet been integrated. However, in the last few years, it has been demonstrated that sequenced-defined bio-oligomers such as oligonucleotides or oligopeptides can find applications in the fields of data storage, biomedicine, drug delivery and nanofabrication because of their versatile physical and chemical properties. Nature on planet earth is directed by poly(phosphoester)s (PPEs) in the form of deoxy & ribonucleic acid (DNA & RNA), and, as pyrophosphates, they store up chemical energy in organisms. Taking the organic polymer synthesis to the next level, we are synthesizing sequence-defined poly(phosphodiester)s using a library of non-nucleosidic monomers. We employ diols as monomers, each bearing a unique functionality such as long chain alkyls, aromatic or heteroaromatic rings. We have adapted the automated solid phase phosphoramidite synthesis commonly used for DNA to make our sequence-defined polymers, allowing us to programme and print specific sequences with ease. Like proteins, these polymers then self-assembly in a sequence-defined fashion to give uniform particles. These nanoparticles were studied using different analytical methods such as DLS, AFM and gel electrophoresis chromatography. Due to their biocompatibility and biodegradability, the PPEs are potentially capable of participating in molecular recognition or directing intracellular drug delivery.