Israel V. M. V. Enoch

The role of encapsulation by β-cyclodextrin in the interaction of raloxifene with macromolecular targets: a study by spectroscopy and molecular modeling

We report the binding of the drug raloxifene with Calf thymus DNA (ctDNA) and bovine serum albumin (BSA) in the presence and absence of β-cyclodextrin (β-CD) and explain the influence of β-cyclodextrin on the binding of the drug to macromolecules. UV-Vis absorption, fluorescence, proton nuclear magnetic resonance and two-dimensional rotating-frame nuclear overhauser effect spectroscopic techniques are used to study the stoichiometry and the binding strength of the complexes. Molecular modeling is used in combination with other techniques to propose the structure of the inclusion complex and the interaction with ctDNA. The Stern–Volmer quenching constants of the interaction of raloxifene with ctDNA in aqueous and in β-CD solution are compared. The competition for binding of ctDNA with raloxifene and Methylene Blue is studied. The apparent binding constant and the number of binding sites for the binding of raloxifene with BSA in aqueous solution are significantly different from those in the presence of β-CD. The influence of β-CD on the binding of the small molecules with biological macromolecules is discussed. We infer that the binding strengths between raloxifene and macromolecules, viz., ctDNA and BSA are influenced by the β-CD encapsulation. These results may suggest new ways to tune the drug binding to biomacromolecules by encapsulating specific moieties of drugs.

Binding of a chromen-4-one Schiff’s base with bovine serum albumin: capping with β-cyclodextrin influences the binding

This work deals with the synthesis of 6-methyl-3-[(4′-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound’s binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 104 M−2. The structure of host–guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC–BSA (1.73 × 105 M−1) and β-cyclodextrin-complexed MMPIMC–BSA (9.0 × 104 M−1) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin.

Tuning the binding of coumarin 6 with DNA by molecular encapsulators: effect of β-cyclodextrin and C-hexylpyrogallol[4]arene

We report in this paper that the binding of coumarin 6 (C6) to DNA can be tuned by complexing it with host structures, viz. β‐cyclodextrin (β‐CD) and C‐hexylpyrogallol‐4‐arene (C‐HPA). Because host molecules are used as carriers of small molecules onto target sites, the exposed part of the guest molecule needs to be found out, and the relationship between the host : guest ratio and the mode of binding with the target macromolecule, that is, the DNA needs to be analyzed, in order to comprehend the preferred binding moiety and tune the binding. In this paper, the formation of the inclusion complex of C6 with β‐CD and with C‐HPA is studied by UV‐visible, fluorescence, 2D rotating‐frame nuclear Overhauser effect correlation spectroscopy and diffusion‐ordered spectroscopy nuclear magnetic resonance spectra and molecular modeling. C6 forms a 1:1 complex with β‐CD and a 1:2 complex with C‐HPA. The studies on the protonation of C6 in the presence and the absence of the host molecules suggest that the chromone part of C6 is outside the β‐CD molecule, whereas it is fully covered by C‐HPA. The binding of C6 with calf thymus DNA (ctDNA) occurs through intercalation and hydrogen bonding, and the host–guest structures remain intact on binding with ctDNA. The oxygens of the C6 molecules are exposed when inside the host molecules and aid in the hydrogen bonding with DNA. Copyright

Isolation of Prunin from the fruit shell of Bixa orellana and the effect of β-cyclodextrin on its binding with calf thymus DNA.

Naringenin-7-O-glucoside [Prunin (Pru)] was isolated from the fruit shell of Bixa orellana L. The binding of Pru with calf thymus DNA (ctDNA) and the influence of cyclomaltoheptaose (β-cyclodextrin, β-CD) on the binding were studied by absorption and fluorescence spectroscopic techniques. The comparison of the binding modes of Pru/β-CD and ctDNA-Pru/β-CD suggested that β-CD extracted Pru from DNA for forming inclusion complex. Molecular modeling gave added support to the above results. Fluorescence microscopy was used to visualize the effect of β-CD on the bindings.

Alteration of the Binding Strength of Dronedarone with Bovine Serum Albumin by β-Cyclodextrin: A Spectroscopic Study

We report the influence of β-cyclodextrin on the binding of the drug dronedarone with bovine serum albumin. The stoichiometry, the binding constant, and the mode of binding of the derivative with β-cyclodextrin are studied by UV–Visible absorption, fluorescence, and 2 Dimensional Rotating Frame Overhauser Effect Spectroscopy (2D ROESY NMR) spectroscopic techniques. The structure of the 1:1 inclusion complex is proposed. The binding of free dronedarone with bovine serum albumin and β-cyclodextrin-bound dronedarone are studied by fluorescence quenching and Förster resonance transfer. The decreased magnitude of the Stern–Volmer constant and the binding constant for the interaction of dronedarone with bovine serum albumin in the presence of β-cyclodextrin are articulated. The donor-to-acceptor distances in the presence and the absence of β-cyclodextrin are compared. The binding sites of the dronedarone with bovine serum albumin are reported by molecular modeling. Dronedarone binds to the sub-domain III of bovine serum albumin. The 3-(dibutylaminopropoxy)benzoyl moiety of dronedarone binds with bovine serum albumin. Encapsulation with β-cyclodextrin decreases the binding strength of dronedarone with bovine serum albumin.

The Unusual Fluorescence Quenching of Coumarin 314 by β-Cyclodextrin and the Effect of β-Cyclodextrin on its Binding with Calf Thymus DNA

This paper discusses the binding of a laser dye, Coumarin 314 with β-cyclodextrin, studied mainly by UV-visible spectroscopy, 2D rotating-frame nuclear Overhauser effect spectroscopy (ROESY), steady-state spectroscopy and time-resolved fluorescence spectroscopy. The role of β-cyclodextrin on the binding of Coumarin 314 with calf thymus DNA was investigated. Coumarin 314 shows a hyperchromic shift of absorption and a quenching of fluorescence due to binding with β-cyclodextrin. The fluorescence quenching is non-linear and the reason for the non-linearity is discussed. The unusual fluorescence quenching on Coumarin 314–β-cyclodextrin binding is rationalised from the effect of acidity on absorption, fluorescence, and molecular modelling studies. Additional proof for the mode of binding is given by 2D ROESY. The capped and exposed portions of the Coumarin 314 molecule in the Coumarin 314–β-cyclodextrin complex when binding with calf thymus DNA were visualised based on spectral and molecular modelling studies.

Picking Out Logic Operations in a Naphthalene β-Diketone Derivative by Using Molecular Encapsulation, Controlled Protonation, and DNA Binding.

On–off switching and molecular logic in fluorescent molecules are associated with what chemical inputs can do to the structure and dynamics of these molecules. Herein, we report the structure of a naphthalene derivative, the fashion of its binding to β-cyclodextrin and DNA, and the operation of logic possible using protons, cyclodextrin, and DNA as chemical inputs. The compound crystallizes out in a keto-amine form, with intramolecular N−H⋅⋅⋅O bonding. It shows stepwise formation of 1:1 and 1:2 inclusion complexes with β-cyclodextrin. The aminopentenone substituents are encapsulated by β-cyclodextrin, leaving out the naphthalene rings free. The binding constant of the β-cyclodextrin complex is 512 m−1. The pKa value of the guest molecule is not greatly affected by the complexation. Dual input logic operations, based on various chemical inputs, lead to the possibility of several molecular logic gates, namely NOR, XOR, NAND, and Buffer. Such chemical inputs on the naphthalene derivative are examples of how variable signal outputs based on binding can be derived, which, in turn, are dependent on the size and shape of the molecule.

Binding Interactions of Naringenin and Naringin with Calf Thymus DNA and the Role of β-Cyclodextrin in the Binding

The interaction of naringenin (Nar) and its neohesperidoside, naringin (Narn), with calf thymus deoxyribonucleic acid (ctDNA) in the absence and the presence of β-cyclodextrin (β-CD) was investigated. The interaction of Nar and Narn with β-CD/ctDNA was analyzed by using absorption, fluorescence, and molecular modeling techniques. Docking studies showed the existence of hydrogen bonding, electrostatic and phobic interaction of Nar and Narn with β-CD/DNA. 1:2 stoichiometric inclusion complexes were observed for Nar and Narn with β-CD. With the addition of ctDNA, Nar and Narn resulted into the fluorescence quenching phenomenon in the aqueous solution and β-CD solution. The binding constant Kb and the number of binding sites were found to be different for Nar and Narn bindings with DNA in aqueous and β-CD solution. The difference is attributed to the structural difference between Nar and Narn with neohesperidoside moiety present in Narn.

A Highly Selective Fluorescent Sensor for Pb 2+ Based on a Modified β-Cyclodextrin

A modified cyclodextrin is synthesized as an anthracene derivative of 6-deoxy- 6-aminoethylamino-β-cyclodextrin and characterized using IR, NMR, and mass spectral techniques. The compound acts as a sensor of Pb2+ ions in a pool of several metal ions, by enhancement of fluorescence. The absorption spectrum does not show significant changes on the addition of metal ions. The stoichiometry and the binding constant of the complex are determined using fluorescence data. The enhancement of fluorescence is attributed to the aminoethyl and imino nitrogens of the spacer of anthracene and β-cyclodextrin. The compound is quite stable under the testing conditions and the sensing is attributed to the charge transfer mechanism.

Spectroscopic investigation of interaction of 6-methoxyflavanone and its β-cyclodextrin inclusion complex with calf thymus DNA

The interaction of 6-methoxyflavanone (6MF, 6-methoxy-2-phenyl-4H-1-benzopyran-4-one) with calf thymus DNA (ctDNA) was investigated by absorption spectroscopy, fluorescence spectroscopy, and cyclic voltammetry in the presence and absence of β-cyclodextrin (β-CD) acting as capping agent. Molecular modelling was used to optimise the study of 6MF-β-CD and 6MF-DNA interactions. Enhancement in the fluorescence intensity of 6MF was observed due to the formation of 1 : 1 complex with β-CD. In the presence and absence of DNA, 6MF showed different characteristics such as hyperchromic effect, red shift of absorption spectra and fluorescence quenching of 6MF due to binding between 6MF and ctDNA. The nature of the binding group was found to be different for the 6MF-ctDNA and 6MF-ctDNA-β-CD systems. An increase in fluorescence intensity was observed for the 6MF-ctDNA system while varying the concentration of β-CD due to encapsulation of a part of 6MF in cyclodextrin. The results are compatible with the possibility of the interaction of dihydrobenzopyran-4-one moiety of 6MF with ctDNA as well as with β-CD. Cyclic voltammetric studies confirmed the binding interaction between 6MF and ctDNA in the absence and presence of β-CD and molecular modelling explains the site of the interaction of 6MF with cyclodextrin and ctDNA.