Using open‐tubular capillary electrochromatography with part‐coating column for binding constants determination of β2‐adrenergic receptor with seven drugs

An open‐tubular capillary electrochromatography method has been developed for the determination of binding constants between β₂‐adrenergic receptor (β₂‐AR) and seven drugs. β₂‐AR was oriented immobilized onto one part of inner surface of capillary via microwave‐assisted technical synthesis. According to the linear relationship between coating length and the apparent mobility of analyte, the binding constant (K_b) can be obtained by related theories and equations. The order of K_b values between drugs such as adrenaline hydrochloride, norepinephrine bitartrate, and propranolol hydrochloride with β₂‐AR is well consistent with that reported in the literature. By the method, K_b values between four extracts of Radix Paeoniae Rubra and β₂‐AR were also successfully obtained. Subsequently, computer models were applied to interpret the CEC experiments. And the results proved to be in good agreement with the method. The work, herein, demonstrates the potential of the method in drug‐receptor affinity interactions evaluation and screening of lead compounds from natural sources.     

Rapid analysis of interaction between six drugs and β2‐adrenergic receptor by injection amount‐dependent method

Drug–protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants (K _A ) of six drugs to β ₂‐adrenergic receptor by injection amount‐dependent method using stationary phase containing the immobilized receptor. The values of K _A were calculated to be (25.85 ± 0.035) × 10⁴ m ⁻¹ for clorprenaline, (42.51 ± 0.054) × 10⁴ m ⁻¹ for clenbuterol, (6.67 ± 0.008) × 10⁴ m ⁻¹ for terbutaline, (33.99 ± 0.025) × 10⁴ m ⁻¹ for tulobuterol, (7.59 ± 0.011) × 10⁴ m ⁻¹ for salbutamol and (78.52 ± 0.087) × 10⁴ m ⁻¹ for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β ₂‐AR column. A good correlation was found between the association constants by the current method and radio‐ligand binding assay. Our data indicates that the injection amount‐dependent method is a powerful alternative for rapid analysis of ligand–receptor interactions.     

High‐expression β1 adrenergic receptor/cell membrane chromatography method based on a target receptor to screen active ingredients from traditional Chinese medicines

β‐Adrenergic receptors are important targets for drug discovery. We have developed a new β₁‐adrenergic receptor cell membrane chromatography (β₁AR‐CMC) with offline ultra‐performance LC (UPLC) and MS method for screening active ingredients from traditional Chinese medicines. In this study, Chinese hamster ovary‐S cells with high β₁AR expression levels were established and used to prepare a cell membrane stationary phase in a β₁AR‐CMC model. The retention fractions were separated and identified by the UPLC–MS system. The screening results found that isoimperatorin from Rhizoma et Radix Notopterygii was the targeted component that could act on β₁AR in similar manner of metoprolol as a control drug. In addition, the biological effects of active component were also investigated in order to search for a new type of β₁AR antagonist. It will be a useful method for drug discovery as a leading compound resource.     

New anthracene based Schiff base ligands appended Cu(II) complexes: Theoretical study,DNA binding and cleavage activities

New anthracene based Schiff base ligands L ¹ and H( L ² ), their Cu(II) complexes [Cu( L ¹ )Cl₂] ( 1 ) and [Cu( L ² )Cl] ( 2 ) , (where L ¹  = N¹,N²‐bis(anthracene‐9‐methylene)benzene‐1,2‐diamine, L ²  = (2Z,4E)‐4‐(2‐(anthracen‐9‐ylmethyleneamino)phenylimino)pent‐2‐en‐2‐ol) have been prepared and characterized by elemental analysis, NMR, FAB‐mass, EPR, FT‐IR, UV–Vis and cyclic voltammetry. The electronic structures and geometrical parameters of complexes 1 and 2 were analyzed by the theoretical B3LYP/DFT method. The interaction of these complexes 1 and 2 with CT‐DNA has been explored by using absorption, cyclic voltammetric and CD spectral studies. From the electronic absorption spectral studies, it was found that the DNA binding constants of complexes 1 and 2 are 8.7 × 10³ and 7.0 × 10⁴ M^?1, respectively. From electrochemical studies, the ratio of DNA binding constants K₊/K₂₊ for 2 has been estimated to be >1. The high binding constant values, K₊/K₂₊ ratios more than unity and positive shift of voltammetric E_1/2 value on titration with DNA for complex 2 suggest that they bind more avidly with DNA than complex 1 . The inability to affect the conformational changes of DNA in the CD spectrum is the definite evidences of electrostatic binding by the complex 1 . It can be assumed that it is the bulky anthracene unit which sterically inhibits these complexes 1 and 2 from intercalation and thereby remains in the groove or electrostatic. The complex 2 hardly cleaves supercoiled pUC18 plasmid DNA in the presence of hydrogen peroxide. The results suggest that complex 2 bind to DNA through minor groove binding.     

Interactions of Dissolved dsDNA with Intercalating Drug by Anodic Voltammetry and Spectroscopy. Influence of pH

The interactions of C‐1305 (5‐dimethylaminopropylamino‐8‐hydroxy‐6H‐v‐triazolo[4,5,1‐de]acridin‐6‐one) with DNA were studied using differential pulse voltammetry and UV‐vis spectroscopy. C‐1305 interacts with dsDNA in two ways: by intercalation and by binding to the minor‐groove. For the intercalation at physiological pH (7.4) the values of the binding constant, K₁, and the binding‐site size, n₁, equal 3.36×10⁵ M^?1 and 2.5, respectively. For the weak interactions the K₂ and n₂ parameters equal 0.18×10⁵ M^?1 and 4. In the presence of excess NaCl the weak interactions do not vanish, therefore they are assigned to the minor groove binding. Substantial and complex is the influence of pH.     

Encapsulation‐Induced Remarkable Stability of a Hydrogen‐Bonded Heterocapsule

Remarkably enhanced stability of the self‐assembled hydrogen‐bonded heterocapsule 1?2 by the encapsulation of 1,4‐bis(1‐propynyl)benzene 3 a was found with K_a=1.14×10⁹ M ^?1 in CDCl₃ and K_a2=1.59×10⁸ M ^?2 in CD₃OD/CDCl₃ (10 % v/v) at 298 K. The formation of 3 a @( 1?2 ) was enthalpically driven (ΔH°<0 and ΔS°<0) and there was a unique inflection point in the correlation between ΔH° versus ΔS° as a function of polar solvent content. The ab initio calculations revealed that favorable guest–capsule dispersion and electrostatic interactions between the acetylenic parts (triple bonds) of 3 a and the aromatic inner space of 1?2 , as well as less structural deformation of 1?2 upon encapsulation of 3 a , play important roles in the remarkable stability of 3 a @( 1?2 ).     

Inhibition of Emulsin by D-Gluconhydroximo-1,5-lactone and Related Compounds

At pH 4.5 (citrate buffer), D -gluconhydroximo-lactone ( 2 ), the N-methylurethane 3 and the N-phenylurethane 4 inhibit competitively the hydrolysis of p-nitrophenyl β-D -glucopyranoside by emulsin. The IC₅₀ values of 2, 3 , and 4 were 1.6 × 10^?4, 1.0 × 10^?4, and 5.8 × 10^?6 M , respectively. The K_i values of 2 and 4 were 9.8 × 10^?5 and 2.3 × 10^?6 M , respectively, while D-glucono-1,5-lactone ( 1 ) showed IC₅₀ = 1.1 × 10^?4 M and K_i = 3.7 × 10^?5 M .     

p‐Toluate‐bridged dinuclear Cu(II) complexes in combination with tridentate chelating ligand: Crystal structure,density functional theory calculation,DNA/protein binding and catecholase activity

The dinuclear Cu(II) complexes [Cu₂(L¹)₂(mb)]?ClO₄ ( 1 ) and [Cu₂(L²)₂(mb)]?ClO₄ ( 2 ) (HL¹ = 2‐[(2‐diethylaminoethylimino)methyl]phenol; HL² = 2‐[1‐(2‐diethylaminoethylimino)propyl]phenol; mb = 4‐methylbenzoate) were synthesized and characterized using X‐ray crystal structure analysis and spectroscopic methods. Complexes 1 and 2 are dinuclear with distorted square pyramidal Cu (II) geometries, where Schiff base coordinates with tridentate (N,N,O) chelating mode and mb bridges two metal centres. Optimized structures and photophysical properties of ligands and complexes were calculated using density functional theory and time‐dependent density functional theory methods using B3LYP functional with 6‐31G (d,p) and LanL2MB basis sets. Interactions of the complexes with bovine serum albumin (BSA) and human serum albumin (HSA) were studied using UV–visible absorption and fluorescence spectroscopies and the calculated values of association constants (M^?1) are 1.7 × 10⁵ ( 1 –BSA), 5.7 × 10⁵ ( 2 –BSA), 1.6 × 10⁵ ( 1 –HSA) and 6.9 × 10⁵ ( 2 –HSA). Interactions of the complexes with calf thymus DNA were also investigated and the binding affinities are 1.4 × 10⁵ and 1.6 × 10⁵ M^?1 for 1 and 2 , respectively. Both complexes catalytically oxidize 3,5‐di‐tert‐butylcatechol to 3,5‐di‐tert‐butylbenzoquinone in the presence of molecular oxygen.     

Synthesis and structural and DNA binding studies of mono‐ and dinuclear copper(II) complexes constructed with ─O and ─N donor ligands: Potential anti‐skin cancer drugs

Mononuclear and dinuclear copper(II) complexes with thiophenecarboxylic acid, [Cu(3‐TCA)₂(2,2′‐bpy)] ( 1 ), [Cu(3‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 2 ), [Cu(5‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 3 ) and [Cu₂(2,5‐TDCA)(DMF)₂(H₂O)₂(2,2′‐bpy)₂](ClO₄)₂ ( 4 ) (where 3‐TCA = 3‐thiophenecarboxylic acid; 3‐Me‐2‐TCA = 3‐methyl‐2‐thiophenecarboxylic acid; 5‐Me‐2‐TCA = 5‐methyl‐2‐thiophenecarboxylic acid; 2,5‐TDCA = thiophene‐2,5‐dicarboxylic acid; 2,2′‐bpy = 2,2′‐bipyridyl; DMF = N,N‐dimethylformamide), were synthesized. Compounds 1 – 4 were extensively characterized using both analytical and spectroscopic methods. Additionally, the solid‐state structures of 1 and 4 were unambiguously established from single‐crystal X‐ray diffraction studies. The hexacoordinated Cu(II) centre in 1 (CuO₄N₂) is a distorted octahedral geometry whereas the pentacoodinated 4 (CuO₃N₂) has distorted square pyramidal geometry. Compounds 1 and 4 exhibit intermolecular hydrogen bonding which leads to the formation of two‐ and three‐dimensional supramolecular architectures, respectively. Spectrophotometric and computational investigations suggest that these compounds bind with DNA in minor groove binding such that K_b = 4.9 × 10⁵ M^?1 and K_sv = 3.4 × 10⁵ M^?1, and binding score of ?5.26 kcal mol^?1. The binding affinity of these complexes to calf thymus DNA is in the order 2 > 3 > 4 > 1 . Methyl‐substituted thiophene ring increases the DNA binding affinity whereas unsubstituted thiophene ring DNA binding rate is reduced. The methyl group on the thiophene ring would sterically hinder π–π stacking of the ring with DNA base pairs, and subsequently they are involved in hydrophobic interaction with the DNA surface rather than partial intercalative interaction. Compounds 1 – 4 show pronounced activity against B16 mouse melanoma skin cancer cell lines as measured by MTT assay yielding IC₅₀ values in the micromolar concentration range. The compounds could prove to be efficient anti‐cancer agents, since at a concentration as low as 2.1 μg ml^?1 they exerted a significant cytotoxic effect in cancer cells whereas cell viability was not affected in normal cells.     

Investigation of calcium antagonist–L-type calcium channel interactions by a vascular smooth muscle cell membrane chromatography method

The dissociation equilibrium constant (K _D) is an important affinity parameter for studying drug–receptor interactions. A vascular smooth muscle (VSM) cell membrane chromatography (CMC) method was developed for determination of the K _D values for calcium antagonist–L-type calcium channel (L-CC) interactions. VSM cells, by means of primary culture with rat thoracic aortas, were used for preparation of the cell membrane stationary phase in the VSM/CMC model. All measurements were performed with spectrophotometric detection (237 nm) at 37 °C. The K _D values obtained using frontal analysis were 3.36 × 10⁻⁶ M for nifedipine, 1.34 × 10⁻⁶ M for nimodipine, 6.83 × 10⁻⁷ M for nitrendipine, 1.23 × 10⁻⁷ M for nicardipine, 1.09 × 10⁻⁷ M for amlodipine, and 8.51 × 10⁻⁸ M for verapamil. This affinity rank order obtained from the VSM/CMC method had a strong positive correlation with that obtained from radioligand binding assay. The location of the binding region was examined by displacement experiments using nitrendipine as a mobile-phase additive. It was found that verapamil occupied a class of binding sites on L-CCs different from those occupied by nitrendipine. In addition, nicardipine, amlodipine, and nitrendipine had direct competition at a single common binding site. The studies showed that CMC can be applied to the investigation of drug–receptor interactions.     

Synthesis,crystal structures and DNA/human serum albumin binding of ternary Cu(II) complexes containing amino acids and 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino

Two water‐soluble 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino (pzta)‐based Cu(II) complexes, namely [Cu(l ‐Val)(pzta)(H₂O)]ClO₄ ( 1 ) and [Cu(l ‐Thr)(pzta)(H₂O)]ClO₄ ( 2 ) (l ‐Val: l ‐valinate; l ‐Thr: l ‐threoninate), were synthesized and characterized using elemental analyses, molar conductance measurements, spectroscopic methods and single‐crystal X‐ray diffraction. The results indicated that the molecular structures of the complexes are five‐coordinated and show a distorted square‐pyramidal geometry, in which the central copper ions are coordinated to N,N atoms of pzta and N,O atoms of amino acids. The interactions of the complexes with DNA were investigated using electronic absorption, competitive fluorescence titration, circular dichroism and viscosity measurements. These studies confirmed that the complexes bind to DNA through a groove binding mode with certain affinities (K_b = 4.71 × 10³ and 1.98 × 10³ M^?1 for 1 and 2 , respectively). The human serum albumin (HSA) binding properties of the complexes were also evaluated using fluorescence and synchronous fluorescence spectroscopies, indicating that the complexes could quench the intrinsic fluorescence of HSA in a static quenching process. The relevant thermodynamic parameters revealed the involvement of van der Waals forces and hydrogen bonds in the formation of complex–HSA systems. Finally, molecular docking technology was also used to further verify the interactions of the complexes with DNA/HSA.     

The Effect of Backbone Stereochemistry on the Folding of Acyclic β2, 3‐Aminoxy Peptides

As a new type of foldamer, β‐aminoxy peptides have the ability to adopt novel β N? O turns or β N? O helices in solution. Herein, we describe a new subclass of β‐aminoxy peptide, that is, peptides of acyclic β^{2, 3}‐aminoxy acids (NH₂OCHR₁CHR₂COOH), in which the presence of two chiral centers provides insight into the effect of backbone stereochemistry on the folding of β‐aminoxy peptides. Acyclic β^{2, 3}‐aminoxy peptides with syn and anti configurations have been synthesized and their conformations investigated by NMR, IR, and circular dichroism (CD) spectroscopic, and X‐ray crystallographic analysis. The β N? O turns or β N? O helices, which feature nine‐membered rings with intramolecular hydrogen bonds and have been identified previously in peptides of β³‐ and β^{2, 2}‐aminoxy acids, are also predominantly present in the acyclic β^{2, 3}‐aminoxy peptides with a syn configuration and N? O bonds gauche to the C_α? C_β bonds in both solution and the solid state. In the acyclic β^{2, 3}‐aminoxy peptides with an anti configuration, an extended strand (i.e., non‐hydrogen‐bonded state) is found in the solid state, and several conformations including non‐hydrogen‐bonded and intramolecular hydrogen‐bonded states are present simultaneously in nonpolar solvents. These results suggest that the backbone stereochemistry does affect the folding of the acyclic β^{2, 3}‐aminoxy peptides. Theoretical calculations on the conformations of model acyclic β^{2, 3}‐aminoxy peptides with different backbone stereochemistry were also conducted to elucidate structural characteristics. Our present work may provide useful guidelines for the design and construction of new foldamers with predicable structures.     

Electroanalytical and spectroscopic procedures for examination of interactions between double stranded DNA and intercalating drugs

A method is presented for the electroanalytical characterization of interactions of dsDNA with a drug, under conditions that both agents are dissolved in the phosphate buffer solution and both are electroactive. Normal pulse, square wave, differential pulse, and cyclic voltammetries were employed in the measurements of the drug and dsDNA oxidation signals at carbon electrodes. UV–Vis spectroscopy was used as a non-electrochemical method to support the electroanalytical data. An anticancer drug, C-1311 (5-diethylaminoethyl-amino-8-hydroxyimidazoacridinone), has been selected for the examination. Normal pulse voltammetry was particularly useful in showing that under the conditions employed neither dsDNA nor the drug were adsorbed at the electrode surface. Necessary conditions for the appearance of the well-defined dsDNA voltammetric signal (guanine peak) are: rigorous chemical and biological purity in the cell and appropriate purity of DNA. An analysis of the obtained results confirmed that there were two modes of interaction between C-1311 and dsDNA: by intercalation and electrostatically. In the presence of excess NaCl the electrostatic interactions deteriorate. The binding constants (K ₁ and K ₂, respectively) and the number (n) of nucleic base pairs (bp) and the number (m) of phosphate groups (pg) interacting with one molecule of drug have been determined. For strong interactions (intercalation) the values of the binding constant, K ₁, and the binding-site size, n, equal 3.7 × 10⁴ M⁻¹ and 2.1, respectively. For the weak electrostatic interactions the K ₂ and m parameters equal 0.28 × 10⁴ M⁻¹ and 4.7. The intercalation process is rather slow and its rate (the conditions of pseudo-first-order reaction) was estimated to equal 7 × 10⁻⁴ s⁻¹. The possibility of independent determination of both interacting agents was very useful in the study. Figure Intercalation of C-1311 into a dsDNA fragment     

Study of Activation and Inhibition of Certain Metal Ions to Amylase Catalyzed Reaction by Microcalorimetry

IntroductionMostcomplicatedreactionshappenedinlivingcrea tures ,amongthemenzymecatalyzedreactionisanimpor tantclass .Itissignificantinboththeoryandpracticetoinvestigateenzymecatalyzedreaction .Therearemanyex perimentalmethodssuchasspectrophotometry ,titrimetry ,isotopemethod ,microcalorimetryandsoon ,inwhichmi crocalorimetryisanewoneduetoitshighsensitivityandaccuracy .Wecanstudythewholeprocessoftheheatef fectusingamicrocalorimeter .Sincetheabsorptionorpro ductionofheatisanintrinsicpropertyofe…     

Remarkably selective recognition of iodobenzene derivatives by a macrocyclic bis-Pt(II) metallohost

We designed and synthesized self‐assembled bis‐Pt^II dimer 1? 4 BF₄ with quino[8,7‐b][1,10]phenanthroline as an extended π‐face contact area, which acts as the first artificial receptor with high affinity toward iodinated aromatic compounds significantly based on noncovalent iodine ??? aromatic‐plane interactions in a “side‐on” fashion. Despite their structural similarity to a previously reported metallohost 2 ⁴⁺ that bears 2,2′:6′,2′′‐terpyridine units, a dramatic change in selectivity toward substituted benzene derivatives was observed for 1 ⁴⁺. ¹H NMR spectroscopic titration revealed a high affinity of 1 ⁴⁺ towards haloarenes, with exceptionally large association constants for 2‐iodophenol (K_a=16 000 M ^?1) and 1,2‐diiodobenzene (K_a=21 000 M ^?1), which are 93‐ and 140‐fold higher, respectively, than the values obtained for 2 ⁴⁺. In addition, 1 ⁴⁺ showed a remarkably high affinity and selectivity toward 2,6‐diiodophenol (K_a=35 000 M ^?1), which is an important substructure of the thyroid hormone T₄. X‐ray crystallography and theoretical calculations strongly suggest that “side‐on” iodine ??? aromatic‐plane interactions and π–π stacking contribute to the strong 1,2‐diiodobenzene and 2,6‐diiodophenol binding. The results obtained here give unique and valuable insight into the nature of halogen atom interactions in their “side‐on” region with an electropositive aromatic plane, which may provide useful guidance for designing artificial receptors for iodinated biomolecules.     

Halide‐Anion Binding by Singly and Doubly N‐Confused Porphyrins

The halide‐binding properties of N‐confused porphyrin (NCP, 1 ) and doubly N‐confused porphyrins (trans‐N₂CP ( 2 ), cis‐N₂CP ( 3 )) were examined in CH₂Cl₂. In the free‐base forms, cis‐N₂CP ( 3 ) showed the highest affinity to each anion (Cl^?, Br^?, I^?) with association constants K_a=7.8×10³, 1.9×10³, and 5.8×10² M ^?1, respectively. As metal complexes, on the other hand, trans‐N₂CP 2–Cu exhibited the highest affinity to Cl^?, Br^?, and I^? with K_a=9.0×10⁴, 2.7×10⁴, and 1.9×10³ M ^?1, respectively. The corresponding K_a values for cis‐N₂CP 3–Cu and NCP 1–Cu were about 1/10 and 1/2, respectively, of those of 2–Cu . With the help of density functional theory (DFT) calculations and complementary affinity measurements of a series of trisubstituted N‐confused porphyrins, the efficient anion binding of NCPs was attributed to strong hydrogen bonding at the highly polarized NH moieties owing to the electron‐deficient C₆F₅ groups at meso positions as well as the ideally oriented dipole moments and large molecular polarizability. The orientation and magnitude of the dipole moments in NCPs were suggested to be important factors in the differentiation of the affinity for anions.     

A Reversible Proton Relay Process Mediated by Hydrogen‐Bonding Interactions in [FeFe]Hydrogenase Modeling

A reversible and temperature‐dependent proton‐relay process is demonstrated for a Fe₂ complex possessing a terminal thiolate in the presence of nitrogen‐based acids. The terminal sulfur site (S^t) of the complex forms a hydrogen‐bond interaction with N,N‐dimethylanilinium acid at 183 K. The Fe₂ core, instead, is protonated to generate a bridging hydride at 298 K. Reversibility is observed for the tautomerization between the hydrogen‐bonded pair and the Fe–hydride species. X‐ray structural analysis of the hydrogen‐bonded species at 193 K reveals a short N(H)???S^t contact. Employment of pyridinium acid also results in similar behavior, with reversible proton–hydride interconversion. DFT investigation of the proton‐transfer pathways indicates that the pK_a value of the hydrogen‐bonded species is enhanced by 3.2 pK_a units when the temperature is decreased from 298 K to 183 K.     

Synthesis,characterization, DNA binding,cytotoxicity and molecular docking properties of Cu (II) and Mn (II) complexes with 1,4‐bis (pyrazol‐1‐yl) terephthalic acid

Two novel complexes, [Cu (L)(H₂O)]?H₂O ( 1 ) and [Mn (H₂O)₆] ?L ?H₂O ( 2 ) (L = 1,4‐bis (pyrazol‐1‐yl) terephthalic acid), were synthesized under hydrothermal conditions. They were characterized using elemental analysis, infrared spectroscopy and single‐crystal X‐ray diffraction. Intramolecular weak interactions, such as hydrogen bonds, and intermolecular interactions play important roles in the construction of the complexes. The interaction of these complexes with fish sperm DNA (FS‐DNA) was monitored and binding constants were determined using UV–visible spectroscopy, which revealed their ability to bind to FS‐DNA, with binding constants for the two complexes of 1.88 × 10⁴ M^?1 ( 1 ) and 1.06 × 10⁴ M^?1 ( 2 ). Viscosity experiments further demonstrated the binding of the complexes to DNA. The complexes were further studied using gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complexes investigated through MTT assays in vitro indicated good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments showed that these complexes induced apoptosis of two different cancer cell lines (HeLa and KB cells), demonstrating a significant cancer cell inhibitory rate. Finally, a further molecular docking technique was employed to confirm the binding of the complexes towards the molecular target DNA.     

Kinetics and mechanism of the reaction of sulphur(IV) with N,N′‐ethylene‐bis(sali‐cylidiniminato)manganese‐(III) in aqueous solution

The reaction of (diaqua)(N,N′‐ethylene‐bis(salicylidiniminato)manganese(III) with aqueous sulphite buffer results in the formation of the corresponding mono sulphito complex, [Mn(Salen)(SO₃)]⁻ (S‐bonded isomer) via three distinct paths: (i) Mn(Salen)(OH₂)₂⁺ + HSO₃⁻ → (k₁); (ii) Mn(Salen)(OH₂)₂⁺ + SO₃²⁻ → (k₂); (III) Mn(Salen)(OH₂)(OH) + SO₃²⁻ → (k₃) in the stopped flow time scale. The fact that the mono sulphito complex does not undergo further anation with SO₃²⁻/HSO₃⁻ may be attributed to the strong trans‐activating influence of the S‐bonded sulphite. The values of the rate constants (10⁻²k_i/dm² mol⁻¹ s⁻¹ at 25°C, I = 0.3 mol dm⁻³), ΔH_i^#/kJ mol⁻¹ and ΔS_i^#/J K⁻¹ mol⁻¹ respectively are: 2.97 ± 0.27, 42.4 ± 0.2, −55.3 ± 0.6 (i = 1); 11.0 ± 0.8, 33 ± 3, −75 ± 10 (i = 2); 20.6 ± 1.9, 32.4 ± 0.2, −72.9 ± 0.6 (i = 3). The trend in reactivity (k₂ > k₁), a small labilizing effect of the coordinated hydroxo group (k₃/k₂ < 2), and substantially low values of ΔS^# suggest that the mechanism of aqua ligand substitution of the diaqua, and aqua‐hydroxo complexes is most likely associative interchange (I_a). No evidence for the formation of the O‐bonded sulphito complex and the ligand isomerization in the sulphito complex, (Mn^III‐OSO₂ → Mn^III‐SO₃), ensures the selectivity of the Mn^III centre toward the S‐end of the S^IV species. The monosulphito complex further undergoes slow redox reaction in the presence of excess sulphite to produce Mn^II, S₂O₆²⁻ and SO₄²⁻. The formation of dithionate is a consequence of the fast dimerization of the SO₃₋. generated in the rate determining step and also SO₄²⁻ formation is attributed to the fast scavenging of the SO₃₋. by the Mn^III species via a redox path. The internal reduction of the Mn^III centre in the monosulphito complex is insignificant. The redox reaction of the monosulphitomanganese(III) complex operates via two major paths, one involving HSO₃₋ and the other SO₃²⁻. The electron transfer is believed to be outersphere type. The substantially negative values of activation entropies (ΔS^# = −(1.3 ± 0.2) × 10² and −(1.6 ± 0.2) × 10² J K⁻¹ mol⁻¹ for the paths involving HSO₃₋ and SO₃²⁻ respectively) reflect a considerable degree of ordering of the reactants in the act of electron transfer. © 1999 John Wiley & Sons, Inc. Int J Chem Kinet 31: 627–635, 1999     

Determination of pKa values of some novel benzimidazole salts by using a new approach with 1H NMR spectroscopy

Benzimidazoles and their derivatives including imidazole are studied widely because they exist in the structure of natural products and different drugs. pK_a values are extremely important for drug discovery and improvement in order to determine pharmacokinetic and pharmacodynamic features such as permeation through biological barriers, interactions with the target area or side effects. Acid–base features (pK_a) have great importance not only for physiological characteristics but also for being used as a ligand or changing physico‐chemical features by turning benzimidazoles into salts. Within the scope of this study, a variety of new benzimidazole salts were synthesized, and their characterizations were made by NMR spectroscopy, FTIR spectroscopy and element analysis techniques. The pK_a values of synthesized benzimidazole salts were determined by inflection point approach using integration values obtained with ¹H NMR spectroscopy and Henderson–Hasselbalch analysis. pK_a values of some benzimidazole salts were also determined by potentiometric methods in order to compare those of NMR spectroscopy results. Copyright © 2015 John Wiley & Sons, Ltd.