On the conformational search of a beta CD dendritic derivative: NMR and theoretical calculations working together reveal a donut-like amphiphilic structure

Abstract

The conformational behavior of host molecular systems is intimately related to their performance, bothas molecular containers and as interfaces in biological environments. Thus, it is of great importance tocarry out rational analyses to understand this behavior.In the present study we established a systematic feedback methodology by correlating 1D and 2D NMRdata (1H and NOESY) and theoretical calculations (semiempirical PM6, two-layer method QM/QM andMolecular Dynamics) comprehensively, to elucidate the conformation of a large,flexible poly(ester)dendriticb-cyclodextrin derivative (bCD[G2]-OH).Three models (A: donut-like, B: ball and C: vase) were constructed as suitable candidates to preservethe C7symmetry observed in the1H NMR spectrum.The electronic relative energies, complemented with the experimental chemical shifts provided theinitial criterion to select Model A as the most likely conformation. The selection was validated throughNOESY NMR experiments and calculated chemical shifts by QM/QM. Additionally, the dynamic behaviorwas explored computationally to confirm that the most stable and persistent conformation forbCD[G2]-OH was model A.Our methodology revealed thatbCD[G2]-OH adopts a donut-like arrangement in which hydrophobicpockets are formed and distributed throughout the structure, rendering information about its amphi-philic character, making this molecule a very attractive host