Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Published in: Beilstein journal of organic chemistry Vol. 12; no. 1; pp. 549 - 563
• Main Authors: Rizzi, Vito, Matera, Sergio, Semeraro, Paola, Fini, Paola, Cosma, Pinalysa
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 21.03.2016; Beilstein-Institut
• Subjects: Aqueous solutions; Chemistry; Cyclodextrin; cyclodextrins; Full Research Paper; Hydrophobicity; inclusion complex; NMR; Nuclear magnetic resonance; photodynamic therapy; Stoichiometry; inclusion complex; cyclodextrins; photodynamic therapy
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.12.54

Since several years the inclusion of organic compounds (guests) within the hydrophobic cavity (host) of cyclodextrins (CDs) has been the subject of many investigations. Interestingly, the formation of inclusion complexes could affect the properties of the guest molecules and, for example, the influence of the delivery system can be a method to improve/change the photochemical behavior of the guest. In particular, very recent studies have shown the protective role of CDs preventing the degradation of the encapsulated guest. Starting from this consideration, in this work, only the structure and complexation mode of the inclusion complexes involving 4-thiothymidine (S 4 TdR, a known photosensitizer) and five CDs, namely 2-hydroxypropyl-α-cyclodextrin (2-HP-α-CD), 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (2-HP-γ-CD), heptakis-(2,6-di- O -methyl)-β-cyclodextrin (DIMEB CD) and heptakis-(2,3,6-tri- O -methyl)-β-cyclodextrin (TRIMEB CD) were investigated by different spectroscopic techniques (UV–vis, FTIR–ATR, 1 H NMR) and cyclic voltammetry analysis (CV). This work is necessary for a prospective research on the photoreactivity of S 4 TdR in aqueous environment and in the presence of CDs to prevent its degradation under irradiation. UV–vis, FTIR–ATR and CV measurements suggested the formation of supramolecular structures involving the employed CDs and mainly the pyrimidine ring of S 4 TdR. 1 H NMR analyses confirmed such indication, unveiling the presence of inclusion complexes. The strongest and deepest interactions were suggested when TRIMEB and DIMEB CDs were studied. The S 4 TdR affinity towards CDs was also evaluated by using the Benesi–Hildebrand (B–H) equation at 25 °C employing CV and 1 H NMR methods. The stoichiometry of the interaction was also inferred and it appears to be 1:1 for all examined CDs.