Preparation and study of a series of copolymers incorporating 2-vinyl-4,4-dimethylazlactone (VDMA) is reported. The reactivity ratios for photo-initiated free radical copolymerization of VDMA with methacrylic acid (MAA), acrylic acid (AA), acrylamide (AAm), dimethylacrylamide (DMAA), hydroxyethyl methacrylate (HEMA), methoxy poly(ethylene glycol) methacrylate (MPEG300MA), and 2-methacryloyloxyethyl phosphorylcholine (MPC), were determined by fitting comonomer conversion data obtained by in situ 1H NMR to a terminal copolymerization equation. Semi-batch photo-copolymerizations were then used to synthesize the corresponding VDMA copolymers with constant composition. Their solubility and dissolution behavior, as well as their hydrolysis half-lives under physiological conditions, were determined. P(VDMA-co-MAA) copolymers with 52 to 93 mol % VDMA showed decreasing initial solubility and increasing hydrolysis half-lives with increasing VDMA content. VDMA copolymers with nonionic monomers AAm and DMAA were water soluble only at VDMA contents of 41 and 22 mol % or less, respectively, and showed longer hydrolysis half-lives than comparable MAA copolymers. VDMA copolymers with HEMA and MPEG300MA were found to crosslink during storage, so their hydrolysis half-lives were not determined. VDMA copolymers with 18% zwitterionic MPC showed a much longer half-life and superior initial solubility compared to analogous p(VDMA-co-MAA), identifying this copolymer as a promising candidate for macromolecular crosslinkers in, for example, aqueous layer-by-layer co-depositions with polyamines. (C) 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012