Non-covalent interactions between poly(N-isopropylacrylamide) and small aromatic probe molecules studied by NMR spectroscopy

Abstract

One of the most important goals in drug delivery is to carry drug molecules to their target as selectively and efficiently as possible. To accomplish this goal it is crucial to understand the interactions of carriers and their loading. The interactions between a thermoresponsive potential drug carrier polymer, poly(N-isopropylacrylamide) (PNIPA) and small aromatic probe molecules: phenol, dopamine and indole derivatives including tryptophan were studied by using solution-state NMR spectroscopy. These substances represent structural elements often found in pharmaceutically relevant compounds. The indole ring is an important part of biologically active natural products, it can be found in several plants and animals. To investigate the effect of temperature on binding and the significance of coil-to-globule transition, 1H T1 and T2 relaxation times, 1H one- and two-dimensional nuclear Overhauser effect spectroscopy (NOESY) and diffusion ordered spectroscopy (DOSY) measurements were carried out in D2O and organic solvents. In the case of phenol and indole derivatives a strong interaction was observed above the lower critical solution temperature (LCST), for it to be much weaker below. According to relaxation measurements only the aromatic ring of tryptophan is bound to the polymer. No interaction was observed between dopamine and the polymer.