Microcalorimetric investigation on the formation of supramolecular nanoassemblies of associative polymers loaded with gadolinium chelate derivatives

In this study, isothermal titration microcalorimetry (ITC) and molecular modeling were used to investigate the mechanism of formation of supramolecular nanoassemblies prepared by mixing aqueous solutions of two associative polymers (i.e. polymerised β-CD (pβ-CD) and dextran grafted with lauryl side chains (MD)). Their capacity to entrap a contrast agent for magnetic resonance imaging (a gadolinium (Gd3+) derivative) has been determined by the same methods. ITC experiments have been employed to evaluate the stoichiometry of interaction (N), association constants (K) and thermodynamic parameter variation associated with complexation between hosts and guests involved in this system. The inclusion compounds studied were: as hosts, β-CD and pβ-CD, and as guests, MD, adamantyl amine, and a Gd3+ complex functionalized with adamantane. It has been demonstrated that pβ-CD cavities tend to interact more favourably with MD (K = 25,000 M−1) than with adamantly amine (K = 3650 M−1) and Gd3+ complex (K = 1460 M−1), forming 1:1 complexes, as also confirmed by molecular modeling. Noteworthy, the Gd3+ derivatives, although incorporated in the supramolecular nanoassemblies (by inclusion into the β-CD cavities of pβ-CD), did not destabilize the pβ-CD–MD inclusion complexes, probably because the interaction between pβ-CD and MD was stronger. Finally, the analysis of thermodynamic parameters revealed that the interaction between MD and pβ-CD was entropy driven (|ΔH| < |TΔS|) while the interactions of adamantly amine and Gd3+ complex with β-CD and pβ-CD were enthalpy driven and dominated by van der Walls forces (|ΔH| > |TΔS|).