Biophysical and biochemical investigation on the binding of a manganese–cyanonitrosyl complex with DNA

The interaction of a cyanonitrosyl–manganate complex with DNA has been studied by u.v.–vis spectroscopy, circular dichroism, fluorescence and gel electrophoresis techniques. As the DNA 260 nm band remained insensitive to interaction, the interaction ratio was determined by monitoring the CN⁻→ Mn LMCT band observed at 222 nm, and the interaction ratio was found to be in the complex (D): DNA (P)=1:0.30 from the spectrophotometric titration. The above-mentioned physical measurements indicate that the binding mode is not intercalative and the cyanonitrosyl system is a groove binder.     

Host-guest inclusion complex between β-cyclodextrin and paeonol: A theoretical approach

Host-guest interactions of β-cyclodextrin (β-CD) with paeonol (PAE) were simulated using semi-empirical PM3 and both ONIOM2 [(B3LYP/6-31G*:PM3), (HF/6-31G*:PM3)] methods. The results obtained with PM3 method clearly indicate that the complexes formed are energetically favored with or without solvent, the model 1 (PAE entering into the cavity of β-CD from its wide side by OCH3 group) is found more favored than the model 2 (PAE entering into the cavity of β-CD from its wide side by COCH3 group). Finally, natural bonding orbital (NBO) analysis was performed based on ONIOM2 optimized complexes to quantify the donor–acceptor interactions between PAE and β-CD.     

Theoretical investigation to characterize the inclusion complex of α-lipoic acid and β-cyclodextrin

We simulated the docking of α-lipoic acid (α-LA) in β-cyclodextrin (β-CD) using two models. We considered in this study complexes formed by 1:1 host–guest stoichiometry in vacuo and in aqueous phase, using PM6, DFT and ONIOM2 hybrid calculations. The results obtained with PM6 method clearly indicate that the complexes formed are energetically favored with or without solvent, model 2 (α-LA entering the cavity of β-CD from its wide side by COOH group) is found more favored than model 1 (α-LA entering into the cavity of β-CD from its wide side by cyclic group), the preference being greater in the case of ONIOM2 calculations. In addition, NBO analysis gives that mutual interactions between the donor and acceptor orbitals of α-lipoic acid and β-CD plays an important role to the stabilization of such a complex. Finally, ¹H nuclear magnetic resonance (NMR) chemical shifts of free and complexed α-LA were calculated by the Gauge-Including Atomic Orbital (GIAO) method and compared with available experimental data. The results of GIAO calculations were analyzed and discussed.     

Vibrational and thermodynamic properties of β-HMX: a first-principles investigation

Thermodynamic properties of β-HMX crystal are investigated using the quasi-harmonic approximation and density functional theory within the local density approximation (LDA), generalized gradient approximation (GGA), and GGA + empirical van der Waals (vdW) correction. It is found that GGA well describes the thermal expansion coefficient and heat capacity but fails to produce correct bulk modulus and equilibrium volume. The vdW correction improves the bulk modulus and volume, but worsens the thermal expansion coefficient and heat capacity. In contrast, LDA describes all thermodynamic properties with reasonable accuracy, and overall is a good exchange-correlation functional for β-HMX molecular crystal. The results also demonstrate significant contributions of phonons to the equation of state. The static calculation of equilibrium volume for β-HMX differs from the room-temperature value incorporating lattice vibrations by over 5%. Therefore, for molecular crystals, it is essential to include phonon contributions when calculated equation of state is compared with experimental data at ambient condition.     

New norditerpenoids and a diterpenoid from a sponge that inhibit the lyase activity of DNA polymerase β

Using an assay to detect inhibitors of the lyase activity of DNA polymerase β, bioassay-directed fractionation of a CHCl₃ extract of an unidentified sponge of the family Demospongiae resulted in the isolation of the new diterpenoid 1, the new bis-norditerpenoids 2-3, and the two known compounds spongia-13(16),14-dien-19-oic acid (4), and methylspongia-13(16),14-dien-19-oate (5). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All five compounds inhibited the lyase activity of DNA polymerase β.     

Experimental and computational investigation of the unexpected formation of β-substituted polyoxygenated furans from conveniently functionalized carbohydrates

In the course of our current studies on the reactivity of alkylidenecarbenes, prepared with the trimethylsilylazide/Bu₂SnO method, on conveniently functionalized α-cyanomesylates derived from d-allose, d-arabinose, and d-threose, we have observed the unexpected, but mechanistically interesting formation of enantiomerically β-substituted polyhydroxylated furans. These compounds are the result of a series of cascade fragmentation reactions on unstable intermediates obtained during 1,5C-H insertion reactions from alkylidenecarbenes. The mechanism of the reaction has been investigated by computational methods using DFT analysis.     

Investigation of the inclusion complex of tolfenamic acid with β-cyclodextrin: Geometry and NBO analysis

Quantum chemical calculations were carried out to investigate geometry and driving forces for inclusion complexes of tolfenamic acid (TA) into β-CD (at 1:1 stoichiometry). Two possible orientations of TA in the β-CD cavity were considered. Both PM3MM and ONIOM2 method evidence that TA is encapsulated in the β-CD cavity for A and B orientation. Finally, charge transfer between the donor and acceptor orbitals of each TA and β-CD play an important role to stabilize the inclusion complex.     

Pharmacology and structures of the free base of the anaesthetic kazcaine and its complex with β-cyclodextrin

The base form of the local anaesthetic kazcaine (BFK, [1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine, C₁₈H₂₃NO₃]) and β-cyclodextrin (β-CD) co-crystallized as BFK:β-CD inclusion complex in 1:2 M ratio from a mixture of water and ethanol while the filtered mother liquor yielded crystals of free BFK. X-ray diffraction showed that the crystals of BFK and its inclusion complex with β-CD belong to monoclinic (P2₁/c) and triclinic (P1) space groups, respectively. The crystals of free BFK are stabilized by pairs of C–H?O, C–H?π and ≡C–H?O type interactions and van der Waals contacts. In the 1:2 BFK:β-CD complex the two β-CD molecules are in hydrogen-bonding contact with their primary hydroxyl groups, the 1-(2-ethoxyethyl)-4-ethynyl-piperidine moiety being located in one and the benzoyloxy group of BFK in the other β-CD. This crystal structure is of the channel-type, the β-CD molecules of the 1:2 BFK:β-CD complex interacting with their secondary hydroxyl groups. The pharmacological activities of the 1:2 BFK/β-CD inclusion complex have been determined in mice, rats, porpoises and rabbits and compare favourably with those of kazcaine, procaine, dicaine, lidocaine and trimecaine. The methods used include terminal (superficial), infiltration, conduction anaesthesia, and acute toxicity.     

An investigation of the complexation of a TTF derivative with α-, β- and γ-cyclodextrins in aqueous media

This Letter, describes the complexation of α-, β- and γ-cyclodextrins (1-3) with TTF derivative 4 in water. In particular, we show using ¹H, ¹³C NMR, UV-vis spectroscopy and isothermal titration calorimetry that β-cyclodextrin 2 forms an effective complex with 4. Complex 2·4 can be conveniently disassembled upon the addition of 1-adamantanol.     

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 ??-cyclodextrin (??-CD) acting as capping agent. Molecular modelling was used to optimise the study of 6MF-??-CD and 6MF-DNA interactions. Enhancement in the fluorescence intensity of 6MF was observed due to the formation of 1 : 1 complex with ??-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-??-CD systems. An increase in fluorescence intensity was observed for the 6MF-ctDNA system while varying the concentration of ??-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 ??-CD. Cyclic voltammetric studies confirmed the binding interaction between 6MF and ctDNA in the absence and presence of ??-CD and molecular modelling explains the site of the interaction of 6MF with cyclodextrin and ctDNA.     

Photochemically induced fluorescence investigation of aβ-cyclodextrin: Azure A inclusion complex and determination of analytical parameters

The photooxidation of Azure A and fluorescence properties of Azure A and its photoproduct have been investigated in aqueous media and in the presence of-cyclodextrin (-CD). The fluorescence intensity of the complex formed between the photoproduct and -CD was found to be three times higher than that of the uncomplexed Azure A photoproduct. A complex formation constant of 110±40 M^–1 was calculated using the Benesi-Hildebrand treatment of the fluorescence emission data. Although the stoichiometry of the Azure A photoproduct: -CD complex was found to be 1: 1, it seems that the Azure A structure is only partially included. Calibration graphs were plotted for the free Azure A photoproduct and the photogenerated product included in -CD. The analytical parameters and quantification limits were determined.     

Synthesis and characterization of inclusion complex of the vasodilator drug minoxidil with β-cyclodextrin

The inclusion complex of β-cyclodextrin and minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) was synthesized using two methods—kneading and freeze-drying—and characterized by UV-Vis spectroscopy, infrared spectroscopy, powder X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis, and nuclear magnetic resonance spectroscopy. These techniques have demonstrated the existence of inclusion compound formation between the host and guest with a molar ratio of 1:1. The studies of solubility and the data obtained by nuclear magnetic resonance spectroscopy showed a weak interaction between the guest and the cyclodextrin molecules in solution.     

A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon-carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide-magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yields. When this reaction was conducted with the lithium ester enolates of α-chlorocarboxylic acid esters, allenic esters were obtained. This procedure provides an unprecedented way for the synthesis of β,γ-unsaturated esters and allenic esters from ketones with the construction of a carbon-carbon bond between α- and β-positions.     

Complexes of α-, β-, and γ-cyclodextrins with nitrophenols: A theoretical study of the structure and energy

Detailed quantum mechanical calculations of the interaction of cyclodextrin (α-, β-, and γ-CD) with 4-nitrophenol (I), 4-nitro-2,6-dimethylphenol (II), 4-nitro-3,5-dimethylphenol (III), and their anions (IVVI) with the formation of intercalation complexes are carried out for the first time. The calculations of the compounds are performed within the density functional theory by the hybrid Becke–Lee–Yang–Parr (B3LYP) method with LanL2DZ basis sets. For the α-CD+III and α-CD+VI complexes it is shown that a nitrophenol molecule of III and a nitrophenolate anion of VI are not contained in the α-CD torus, which agrees with the experimental equilibrium constants. It is found that the calculated equilibrium constants of the formation of guest–host complexes with phenolate anions are much larger than those of neutral molecules. The most stable CD complexes with nitrophenols and their anions should be expected for γ-CD. The β-CD complexes when the guest enters into the host cavity are formed only with compounds I, V, and VI.     

Evaluation of the effect of the chiral centers of Taxol on binding to β-tubulin: A docking and molecular dynamics simulation study

Taxol is one of the most important anti-cancer drugs. The interaction between different variants of Taxol, by altering one of its chiral centers at a time, with β-tubulin protein has been investigated. To achieve such goal, docking and molecular dynamics (MD) simulation studies have been performed. In docking studies, the preferred conformers have been selected to further study by MD method based on the binding energies reported by the AutoDock program. The best result of docking study which shows the highest affinity between ligand and protein has been used as the starting point of the MD simulations. All of the complexes have shown acceptable stability during the simulation process, based on the RMSDs of the backbone of the protein structure. Finally, MM-GBSA calculations have been carried out to select the best ligand, considering the binding energy criteria. The results predict that two of the structures have better affinity toward the mentioned protein, in comparison with Taxol. Three of the structures have affinity similar to that of the Taxol toward the β-tubulin.     

Interplay between Molecular Recognition and Redox Properties: A Theoretical Study of the Inclusion Complexation of β-Cyclodextrin with Phenothiazine and its Radical Cation

The PM3 molecular orbital method was employed in the conformational analysis of the inclusion complexation of -cyclodextrin with phenothiazine and its radical cation from a complete and unrestricted geometry optimization. Ab initio calculations at the level of HF/3-21G(d) and B3LYP/3-21G(d) were utilized to determine the electronic structures of the host, guest and their complexes. The results indicated that the complexation of -cyclodextrin with the phenothiazineradical cation was significantly more favorable than that with the neutral one, in good agreement with the experimental observation. The charge-transfer interaction was proposed as a physical reason for such behavior. It is suggested that caution should be given when extrapolating one oxidation state behavior to the supramolecular systems in their other oxidation states.