p-Sulfonatocalixarene versus p-thiasulfonatocalixarene: encapsulation of tenofovir disoproxil fumarate and implications to ESI-MS, HPLC, NMR, DFT and anti-MRSA activities

• Published in: Journal of inclusion phenomena and macrocyclic chemistry 2021-02, Vol.99 (1-2), p.43-59
• Main Authors: Jarange, Asmita B., Patil, Sanhita V., Malkhede, Dipalee D., Deodhar, Shreya M., Nandre, Vinod S., Athare, Sulakshana V., Kodam, Kisan M., Gejji, Shridhar P.
• Format: Article
• Language: English
• Subjects: Adenine; Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Density functional theory; Encapsulation; Food Science; High performance liquid chromatography; Hydrogen bonding; Inclusion complexes; Infrared spectra; NMR; Nuclear magnetic resonance; Organic Chemistry; Original Article; Protons; Stoichiometry
• ISSN: 1388-3127; 1573-1111
• DOI: 10.1007/s10847-020-01022-w

The inclusion complexes of tenofovir disoproxil fumarate (TDF) with p -sulfonato-calix[4]arene (SCX4) and p -sulfanatothiacalix[4]arene (TSCX4) macrocycles are characterized through an array of experiments including 1 H NMR, NOESY, HPLC, HRMS, FT-IR and PXRD in conjunction with the density functional theory. An encapsulation of TDF within SCX4 and TSCX4 macrocycles conduce 1:1 complexes those prevail over 1:2 or 1:3 Stoichiometries which exhibis distinct structural features. A loss of crystallinity accompanying the complexation ascertains the inclusion of the guest within the macrocycle. A comparison of the measured 13 C NMR spectra of the complexes with individual hosts ascertains the cone conformation of SCX4 in such complexes as in its free state. It has been demonstrated that the TDF guest penetrates deeply within the cavity of SCX4 facilitating the hydrogen bonding interactions between adenine protons and the hydroxyl as well as methylene protons of the macrocycle. The measured 1 H NMR spectra thus reveal large upfield signals (δ 8.35, 8.48 ppm) for adenine protons of the SCX4 complex. On the other hand, the partial encapsulation of TDF in TSCX4 reflects in the deshielding of hydroxyl protons in the measured 1 H NMR spectra. The characteristic C=N and SO stretching vibrations in the infrared spectra engender’frequency shifts’ in the opposite directions compared to the individual host or guest. A simple reverse phase high performance liquid chromatography method is presented. The adenine encapsulation further has been qualitatively correlated with MRSA activities.