On the conformational search of a βCD 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, both as molecular containers and as interfaces in biological environments. Thus, it is of great importance to carry out rational analyses to understand this behavior.In the present study we established a systematic feedback methodology by correlating 1D and 2D NMR data (1H and NOESY) and theoretical calculations (semiempirical PM6, two-layer method QM/QM and Molecular Dynamics) comprehensively, to elucidate the conformation of a large, flexible poly(ester) dendritic β-cyclodextrin derivative (βCD[G2]-OH).Three models (A: donut-like, B: ball and C: vase) were constructed as suitable candidates to preserve the C7 symmetry observed in the 1H NMR spectrum.The electronic relative energies, complemented with the experimental chemical shifts provided the initial criterion to select Model A as the most likely conformation. The selection was validated through NOESY NMR experiments and calculated chemical shifts by QM/QM. Additionally, the dynamic behavior was explored computationally to confirm that the most stable and persistent conformation for βCD[G2]-OH was model A.Our methodology revealed that βCD[G2]-OH adopts a donut-like arrangement in which hydrophobic pockets are formed and distributed throughout the structure, rendering information about its amphiphilic character, making this molecule a very attractive host.