Inclusion complexation of naproxen with cyclosophoraoses and succinylated cyclosophoraoses in different pH environments

• Published in: Journal of Inclusion Phenomena and Macrocyclic Chemistry 2012-12, Vol.74 (1-4), p.325-333
• Main Authors: Kwon, Chanho, Choi, Youngjin, Jeong, Daham, Kim, Jun Gull, Choi, Jae Min, Chun, Sohyun, Park, Seyeon, Jung, Seunho
• Format: Article
• Language: English
• Subjects: Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Food Science; Organic Chemistry; Original Article
• ISSN: 0923-0750; 1573-1111
• DOI: 10.1007/s10847-012-0119-7

Cyclosophoraoses [cyclic β-(1,2)-glucan, Cys] isolated from Rhizobium leguminosarum biovar trifolii TA-1 have unique structures and high solubility, which make it a potent solubilizer for host–guest inclusion complexation. Succinylated cyclosophorasoses (S-Cys) were also synthesized by chemically modifying isolated cyclosophoraoses. In ultraviolet-visible studies using naproxen (NAP), Cys was shown to form the most stable complexes with NAP ( K 1:1  = 2457.9 M −1 ), which was followed by the negatively charged S-Cys ( K 1:1  = 357.1 M −1 ) at pH 3.4. A further strong reduction in the complex stability constant was observed at pH 7.5. When the reduction in the stability constant was compared with other cyclic oligosaccharides (Cys; 119.2 M −1 , CD; 14.48 M −1 and HP-CD; 6.75 M −1 ), S-Cys ( K 1:1  = 5.6 M −1 ) was shown to have the highest decrease in stability constant. These results suggest that the S-Cys could regulate the efficiency of inclusion complexation at external pH values. NMR studies of complex formation between NAP and Cys also showed a different correlation pattern at pH 3.4 and 7.5. This difference in correlation demonstrates that the inclusion complexes between Cys and NAP formed as a result of the differential charge distribution of the carboxyl groups of NAP. The pH-dependent inclusion behavior of Cys for NAP was also evaluated using molecular docking simulations.