Sustainable Nanochemistry

Polymer Theranostics & Bioenergy

Dr. Vasco Bonifácio pioneered the synthesis of biodendrimers in Portugal. In 2008, under the project Just in time dendrimers (PTDC/CTM/099452/2008) he designed a new class of dendrimers. The synthesis of polyurea (PURE) dendrimers was first published in 2012 (Angew. Chem. Int. Ed. 2012, 51, 5162). PURE dendrimers are water-soluble, biocompatible, non-cytotoxic, non-hemolytic and present an unusual pH-dependent blue non-traditional intrinsic luminescence (NTIL). PURE dendrimers are structurally similar to PAMAM dendrimers (pioneered by Prof. Tomalia in 1985), differing in the backbone functional groups, were amides (NH-CO) are replaced by ureas (NH-CO-NH). The simple incorporation of urea groups confer dendrimers new properties (e.g. reduced toxicity, no haemolytic activity, high fluorescence) and functionalization opportunities (e.g. urea chemistry). The synthesis of PURE dendrimers in made in supercritical carbon dioxide and follows an isocyanate-free, divergent step-wise polymerization [A3+B3 strategy], using carbon dioxide as solvent and as a carbon source (C1-feed stock) (Figure 1).

Figure 1. Green synthesis and chemical structure of a PUREG4 dendrimer.

Biodendrimers are currently undergoing a transition to clinics and are expected to soon make part of our day life, both as formulations for drug/gene delivery, or as novel polymer therapeutics, with intrinsic antimicrobial, antifungal or anticancer activity. In May 2019, Vivagel (developed by Prof. Tomalia), a non-antibiotic therapy for bacterial vaginosis, was the first FDA approved dendrimer-based formulation.
Since its discovery PURE dendrimers have been investigated in many different applications, especially in the field of Nanomedicine, and are expected to strongly contribute to the advance of many fields of science (
Scheme 1).

Scheme 1. PURE dendrimers for polymer theranostics. Publications 32, 35, 37, 42, 48, 51, 52.

Another challenging and emergent application of PURE dendrimers is in the bioenergy field. Playing with urea chemistry, we converted aromatic poly(urea amidoamidine) (PURAM) dendrimers into poly(imidazolone amine) (PIMAM) donor-acceptor dendrimers that show a photodiode-like behaviour (Scheme 2). Also, after rational design, other dendrimers were syntesised and are being investigated as supercapitor electrodes for microbial fuel cells.

Scheme 2. PURE dendrimers for bioenergy.