A major challenge in pharmaceuticals for clinical applications is to alter the solubility, stability, and toxicity of drug molecules in living systems. Cyclodextrins (CDs) have the ability to form host-guest inclusion complexes with pharmaceuticals for further development of new drug formulations. The inclusion complex of clomiphene citrate (CL), a poorly water-soluble drug, with native β-cyclodextrin (β-CD) was characterized by a one and two-dimensional nuclear magnetic resonance (NMR) spectroscopic approach and also by molecular docking techniques. Here we report NMR and a computational approach in preferential isomeric selection of CL, which exists in two stereochemical isomers, enclomiphene citrate (ENC; E isomer) and zuclomiphene citrate (ZNC; Z isomer) with β-CD. β-CD cavity protons, namely, H-3' and H-5', experienced shielding in the presence of CL. The aromatic ring protons of the CL molecule were observed to be deshielded in the presence of β-CD. The stoichiometric ratio of the β-CD:CL inclusion complex was observed by NMR and found to be 1:1. The overall binding constant of β-CD:CL inclusion complexes was based on NMR chemical shifts and was calculated to be 50.21 M . The change in Gibb's free energy (∆G) was calculated to be -9.80 KJ mol . The orientation and structure of the β-CD:CL inclusion complexes are proposed on the basis of NMR and molecular docking studies. 2D H- H ROESY confirmed the involvement of all three aromatic rings of CL in the inclusion complexation with β-CD in the solution, confirming the multiple equilibria between β-CD and CL. Molecular docking and 2D H- H ROESY provide insight into the inclusion complexation of two isomers of CL into the β-CD cavity. A molecular docking technique further provided the different binding affinities of the E and Z isomers of CL with β-CD and confirmed the preference of the Z isomer binding for β-CD:CL inclusion complexes. The study indicates that the formation of a hydrogen bond between -O- of CL and the hydrogen atom of the hydroxyl group of β-CD was the main factor for noncovalent β-CD:CL inclusion complex formation and stabilization in the aqueous phase.
In this work, molecular simulation methods combining molecular docking and the structure elucidation of inclusion complex of cephalexin/β-cyclodextrin (β-CD) was determined using 1H NMR. Molecular docking studies showed that the complex formation process between β-CD and cephalexin was favourable and spontaneous because of negative values of binding energies. Molecular docking studies also confirmed the entry of aromatic ring into the cavity. Molecular mechanics studies were performed for aromatic ring of cephalexin, in different orientations and from both cavity ends, to measure the
parameters of inclusion depth and mode of entry. The resultant structure was studied for HOMO-LUMO gap to validiate the method. The final structure was established using 1H NMR, molecular mechanics, HOMO-LUMO gap and molecular docking.
Many linear polymers containing water‐attracting groups spread uniformly at the airwater interface. The spreading property of polymethyl methacrylate is due to the ester groups which serve as anchors and promote spreading. The spreading of polystyrene, although it is a pure hydrocarbon, appears probably to be due to the end groups in each polymer molecule, introduced at the termination of the chains which act as anchors and facilitate spreading.
The surface pressure extended by the films of the high polymers is a sort of two‐dimensional swelling pressure. The distinguishing feature of these films is their high compressibility in the rectilinear portion of the F–A curve.
The limiting areas for F–A curves are not independent of the concentrations of spreading solutions as might be expected. The primary cause of this phenomenon in the case of high polymers appears to be a more or less coherent sponge‐ or felt‐like structure which develops at high concentration. The linear polymers, like polystyrene, become coiled up statistically and at higher concentration the coils become interlocked and produce an imperfectly spread film.
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