Structural and theoretical-experimental physicochemical study of trimethoprim/randomly methylated-β-cyclodextrin binary system

Enhanced semiempirical QM methods for biomolecular interactions

“…The very good accuracy of SQM-DH methods for biomolecular interactions in comparison to high-level CCSD(T)/CBS references begs the question of whether these methods might not be good enough to replace DFT-D methods for the accurate computation of such interactions in medium sized systems. Accordingly many studies on host/guest or inclusion complexes were published over the last years [100–104] , as well as on molecular tweezers [105] , non-covalent complexation in general [106–110] , and supramolecular chemistry [111,112] , most of them with very promising results at SQM-DH level. Muddana and Gilson presented a study on 29 CB7 host-guest systems with PM6-DH +/COSMO based on their ‘minima mining’ (M2) approach for predicting binding affinities and found good agreement with experiment [113] .…”

Recent Progress in Treating Protein–Ligand Interactions with Quantum-Mechanical Methods

“…The most important model systems with relation to protein/ligand interactions are host/guest systems, for which SQM-DH methods are now routinely applied [ 12 , 96 , 97 , 98 , 99 ]. Muddana et al calculated free energies of binding with their minima mining approach; i.e.…”

Preparation and characterization of Trimethoprim inclusion complex with Methyl-β-Cyclodextrin and determination of its antimicrobial activity

“…Spectra of the binary systems do not show new bands, indicating the absence of new bonds. In the region above 2500 cm -1 a wider band is observed probably due to a superposition of spectral features of the OH stretching of the CD and the NH 2 stretching of the TMP [7]. Significant changes are observed in the area between 1600 and 1400 cm -1 assigned to C=C aromatic stretching in free TMP due to the interaction between this region of the drug and cyclodextrin cavity [7] and an enlargement of the bands at 1030 cm -1 of the MBCD is observed due to the establish of interaction during complexes formation.…”

“…The FTIR spectrum of TMP shows bands between 1653.34 and 1421.08 cm -1 that can be assigned to C=C and C=N stretching of the aromatic ring; 1234.58 cm -1 corresponding to the OCH 3 aromatic group vibration; vibration of the C-N bond at 1336.77cm -1 in the aromatic primary amine, and NH 2 stretching at 3468.39 and 3403.64 cm -1 [7]. In the MBCD spectrum it is observed a broad band at 3368.18 cm -1 corresponding to residues of OH methylated groups, and a strong band at about 1030.82 cm -1 attributed to the OCH 3 group.…”

“…In particular, β-cyclodextrin shows a low aqueous solubility (1.85% w/v at 25°C) due to its rigid structure resulting from intramolecular formation of hydrogen bonds between its secondary hydroxyl groups [4]. In order to counteract the low solubility of this cyclodextrin, chemically modified derivatives with higher solubility and lower toxicity have been developed, such as 2,3,6 methyl-β-cyclodextrin (MBCD), randomly methylated in position 2, 3 and 6 hydroxylpropyl-β-cyclodextrin (HPBCD), formed by substitution of the hydroxyl in position 2, 3 and 6 with 2-hydroxypropyl substituents [4,5] The complexation of TMP with MBCD and HPBCD in aqueous solution was also studied by other authors [6,7]. However, the full characterization of the formed complexes in solid state, including their dissolution profile and antibacterial activity determination was never performed.…”