Enzymatic Synthesis of Poly(β-Amino Ester) Copolymer With High Potency in Eliminating Gram-Negative Bacteria

The functional lactone 2-Methyl-2-propanyl-7-oxo-1,4-oxazepane-4-carboxylate (BocOP), containing a protected secondary amino group, is synthesized through oxone-mediated Baeyer-Villiger oxidation. After that, the homopolymerization kinetics of BocOP catalyzed by immobilized Candida antarctia lipase B (Novozym 435, N435) are investigated. The N435 can efficiently catalyze the conversion of BocOP into poly(β-amino ester) (PAE). Then, the N435 is subsequently employed to synthesize copolymers of BocOP and ε-caprolactone (CL) using methoxypolyethylene glycols (mPEG) as initiators. The study shows that BocOP copolymerized with CL to produce a random PAE copolymer. Following deprotection, the PAE copolymers containing discoverable secondary amino groups demonstrate a preferent bactericidal effect against Gram-negative bacteria. The preference arises from the capacity of PAE copolymers to permeabilize the bacterial outer membrane, subsequently slightly compromising the inner membrane and resulting in the death of Gram-negative bacteria. Furthermore, the PAE copolymers exhibit a comparatively low hemolysis and cytotoxicity.