Structure and Self-Aggregation of Mono- and Bis(cyclodextrin) Derivatives in Aqueous Media: Fluorescence, Induced Circular Dichroism, and Molecular Dynamics

Fluorescence and circular dichroism techniques were used to study the water solution behavior of those mono- and bis beta CDs derivatives whose appended group or spacer between beta CDs contain the fluorescent 1,3-diphenoxy moiety (OB), i.e., 6[4-((3-(prop-2-ynyloxy)phenoxy)methyl]-1H-1,2,3-triazol-1-yl]6-deoxy-beta CD (m beta CD) and 1,3-bis((1-(6'deoxy-beta CD-6'-yl)-1H-1,2,3-triazol-4-yl)methoxy)benzene (b beta CD), as well as their 1,3-bis(propargyloxy)benzene (POB) model compound in the presence of beta CD. Molecular dynamics calculations were also employed to simulate the conformational behavior of m- and b beta CD derivatives, as well as the POB/beta CD complexation and self-association of m beta CD in the presence of water. Unfortunately, fluorescence techniques are not very useful for studying these systems as the fluorescence properties of the OB chromophore hardly change with the microviscosity and polarity of the environment. However, the combination of the induced circular dichroism measurements and molecular dynamics simulations permitted us to clarify the structure of rn beta CD, b beta CD, and POB/beta CD complexes in aqueous solution. Self-inclusion of the appended group (or spacer) for m beta CD (b beta CD) is rather unlikely. However, m beta CD may associate as tail-to-head n-mers or as tail-to-tail dimers. In the latter complexes OB groups are axially oriented relative to the main beta CD axis and partially outside the cavity. These association processes, which are probably responsible for the m beta CD low solubility in water, may compete with any guest complexation.