Designing of Poly(l-lactide)-Nicotine Conjugates: Mechanistic and Kinetic Studies and Thermal Release Behavior of Nicotine.

The current work focuses on the ring-opening polymerization (ROP) of l-lactide (LLA) using N-heterocyclic functionalized molecules as an initiator for the synthesis of metal-free poly(l-lactide) (PLLA) conjugates. With this motivation, we have used a drug molecule, nicotine, having N-heterocyclic functionality as the initiator for the synthesis of PLLA conjugates. Structural characterizations carried out using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, Fourier transform infrared, and NMR establish the reacting species during polymerization in the absence of any side reactions. However, side reactions occurred because of the absence of steric hindrance when polymerization is initiated using nicotine in the presence of benzyl alcohol. Accordingly, we report here a detailed investigation on the mechanism of nicotine as an initiator and propose an anionic-based mechanism for the ROP of LLA. Studies on the kinetics parameters have been performed for the nicotine-initiated ROP of LLA and have found that polymerization proceeds with a first-order dependence on both the monomer and initiator concentrations with a low activation energy of 4.9 kcal·mol(-1). Further, thermal release studies performed by hyphenated thermogravimetric-Fourier transform infrared analysis found that nicotine is released along with reduced toxins from these synthesized PLLA-nicotine conjugates. Thus, these PLLA-nicotine conjugates can in turn open up a new era in tobacco industries for the preparation of synthetic cigarettes and also in biomedical applications for drug delivery purposes. Herein, a few preliminary experiments using another drug molecule, nicorandil, having similar N-heterocyclic functionality were also conducted to support the role of nicotine as an initiator for the synthesis of PLLA conjugates.