Highly heterotactic poly(4-vinyl pyridine)s (P4VPs) with the fraction of mr content (fmr) > 0.81 were synthesized by free radical polymerization of 4-vinyl pyridine (4VP) with randomly methylated beta-cyclodextrin (beta-RMCD) in acidic aqueous media of HNO3 and CF3COOH at 40 degrees C. The heterotacticity of P4VP strongly depended on the neutralization of 4VP. The complete neutralization of 4VP with HNO3 or CF3COOH increased the heterotacticity of P4VP, whereas atactic P4VP was obtained in water. The partial decomposition of beta-RMCD by HCl reduced the heterotacticity of P4VP (fmr approximate to 0.74). The structures of inclusion complexed monomers were determined by Job's plot, 2D NMR with nuclear Overhauser enhancement spectroscopy analyses, and simulation by MM2. The 1:2 complex with [beta-RMCD]:[4VP] with meso placement of 4VPs in beta-RMCD was formed when 4VP was completely neutralized with acid, whereas the 1:1 complex was formed in water. The mechanism of heterospecific control by using beta-RMCD was proposed. (c) 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012