Synthesis of 6-mono-6-deoxy-beta-cyclodextrins substituted with isomeric aminobenzoic acids. Structural characterization, conformational preferences, and self-inclusion as studied by NMR spectroscopy in aqueous solution and by X-ray crystallography in the solid state.
The synthesis, purification, and characterization of mono-6-modified-beta-cyclodextrins bearing N-attached o-, m-, and p-aminobenzoic acids (2, 3, and 4, respectively) are presented. The structures in aqueous solution were investigated using one- and two-dimensional NMR spectroscopy. Detailed assignment of the spectra together with intramolecular NOE correlations revealed the way each of the isomeric appendages is positioned relative to the macrocyclic cavity. No self-inclusion is observed. The o-isomer 2 turns inward over the top of the primary side and interacts with specific protons of the substituted glucopyranose unit A and those of a neighboring unit. The m-isomer 3 displays two conformations, where the substituent resides above the primary side in a tilted manner and interacts either with the previous or the next unit. We propose that the carboxyl groups in both 2 and 3 are localized through H-bonding with one or two, respectively, primary hydroxyl groups of the neighboring glucopyranose units. In a similar positioning of the aromatic ring of the p-isomer 4, the hydrophilic carboxyl end is fully exposed to the aqueous environment. The X-ray structure of 4 shows that the solution conformation has evolved such that in the crystalline state, the aromatic moiety is inserted through its carboxyl part inside another CD where it establishes intermolecular H-bonds with inward-turned primary OH groups. Besides this stabilization, 4 forms parallel and antiparallel supramolecular chains in the crystal that are additionally stabilized by direct H-bonds.
Eliadou
Kyriaki
K
Institute of Physical Chemistry, National Center for Scientific Research Demokritos, Ag. Paraskevi 15310, Athens, Greece.
Giastas
Petros
P
Yannakopoulou
Konstantina
K
Mavridis
Irene M
IM
D062365:Aminobenzoates / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000379:methods; D003505:Cyclodextrins / Q000138:chemical synthesis*; D005947:Glucose / Q000737:chemistry; D006860:Hydrogen Bonding; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D011714:Pyrans / Q000737:chemistry; D012996:Solutions; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins
D062365:Aminobenzoates; D003505:Cyclodextrins; D011714:Pyrans; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; D005947:Glucose; C031215:betadex