Biomimetic Model of Coenzyme B12: Aquabis(ethane‐1,2‐diamine‐κN,κN′)ethylcobalt(III) – Its Kinetic and Binding Studies with Imidazoles and Amino Acids and Interactions with CT DNA

Pseudo‐first‐order reaction kinetics and binding studies of trans‐[Co(en)₂(Et)H₂O] complex with 1H‐imidazole, substituted 1H‐imidazoles, histidine, histamine, glycine and glycine ethyl ester were investigated by means of spectrophotometric techniques. Equilibrium constants were determined as a function of pH at 25°. Binding and kinetic studies were correlated to basicity and steric hindrance. From the equilibrium data, it was found that the entering nucleophile is participating in the transition state, an I_d mechanism is proposed. The effect of the incoming ligands on the complex was studied by molecular mechanics. The interaction of trans‐[Co(en)₂(Et)H₂O] with CT DNA was studied spectrophotometrically.     

Catalytic effect of CTAB reverse micelles on the kinetics of dissociation of bis(2,4,6–tripyridyl-s-triazine) iron(II)

The kinetics of dissociation of bis(2,4,6–tripyridyl-s-triazine) iron(II), ([Fe(TPTZ)₂]²⁺) has been studied in CTAB/chloroform/hexane reverse micellar medium. In the absence of acid, the reaction is immeasurably slow and does not go to completion in conventional aqueous medium but is markedly accelerated and takes place with a rate constant equal to 55.3 × 10^?3 s^?1 and goes to completion in reverse micelles. The significant increase in rate is attributed to the special properties of the water pool in the reverse micelles like low dielectric constant, nucleophilic effect of Br^- ion, and favorable partitioning of TPTZ in the organic phase. The rate of the reaction decreases with increase in W (=[H₂O]/[CTAB]) at constant CTAB concentration and remains constant with increase in CTAB at fixed W. The results are compared with other closely related systems.     

Synthesis, characterization, DNA-binding, photocleavage, cytotoxicity and docking studies of Co(III) mixed ligand complexes

A new ligand, (2-ethoxy-6-(1H imadazo[4,5-f][1,10]phenanthroline-2-yl)phenol) (HEPIP) and its three Co(III) complexes [Co(phen)₂(HEPIP)](ClO₄)₃ (1), [Co(bpy)₂(HEPIP)](ClO₄)₃ (2) and [Co(dmb)₂(HEPIP)](ClO₄)₃ (3) have been synthesized and characterized. All three Co(III) complexes exhibited antitumor activity against four human tumor cell lines. The interaction of these complexes with calf thymus DNA was studied by absorption and emission spectroscopy, viscosity measurements and DNA cleavage assays. The DNA-binding constants of complexes 1, 2 and 3 were determined as 6.13 × 10⁵, 4.46 × 10⁵ and 3.72 × 10⁵ M^?1, respectively. The complexes appear to interact with DNA through intercalation. Studies on the mechanism of photocleavage indicated that both superoxide anion radical and singlet oxygen may play an important role.     

Asymmetric amplification by kinetic resolution using a racemic reagent: example in amine acetylation

The reaction of a racemic reagent on a mixture of enantiomers with small ee (ee=enantiomeric excess) has been studied for amine acylation. A substantial asymmetric amplification could be realized, for example, from 67 to >95.5 ee. The combination of asymmetric amplifications is subsequently discussed. Two sequential asymmetric amplifications, one using a racemic reagent and another using a positive nonlinear effect allowed us to start from 1.5 % ee and end with a large amount of a product of 97 % ee.     

Synthesis, characterization and DNA-binding characteristics of Ru(II) molecular light switch complexes

A series of four polypyridyl Ru(II) complexes such as [Ru(L)₄(PIP)]²⁺ and [Ru(L)₄PPIP]²⁺ where L is 4-amino pyridine and Pyridine (PIP?=?2-phenylimidazo[4,5-f] [1, 10] phenanthroline), (PPIP?=?2-(4??-phenoxy-phenyl) imidazo[4,5-][1, 10]phenanthroline) have been synthesized and characterized by elemental analysis, physicochemical methods such as UV?Cvis, IR and NMR spectroscopic techniques. The DNA-binding behavior of these complexes was investigated by electronic absorption titrations, fluorescence spectroscopy, viscosity measurements and salt-dependent studies. The experimental results indicate that all these complexes can bind to DNA through an intercalation mode, the DNA-binding affinities of these complexes follow the order [Ru(4-APy)₄(PPIP)]²⁺(1)?>?[Ru(Py)₄PPIP]²⁺(2)?>?[Ru(4-APy)₄(PIP)]²⁺(3)?>?[Ru(Py)₄PIP]²⁺(4). Noticeably, these complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA. Further, all four complexes screened for their antimicrobial activity indicate that the complexes show appreciable activity against Escherichia coli and Neurospora Crassa. In addition, in the presence of Co²⁺, the emission of DNA-[Ru(L₄)PPIP/PIP]²⁺ can be quenched and recovered by the addition of EDTA, which exhibited the DNA ??light switch?? properties.     

Hyperaromatic stabilization of arenium ions: acid-catalyzed dehydration of 2-substituted 1,2-dihydro-1-naphthols

Rate constants for acid-catalyzed dehydration of cis-2-substituted 1,2-dihydro-naphthols are well correlated by the Taft relationship log k = -0.49 - 8.8σ(I), with minor negative deviations for OH and OMe. By contrast the trans substituents show a poor correlation with σ(I) and in most cases react more slowly than their cis isomers. The behavior is consistent with rate-determining formation of a 2-substituted carbocation (naphthalenium ion) intermediate that for cis reactants possesses a 2-C-H bond suitably oriented for hyperconjugation with the charge center. For the trans isomers the 2-substituent itself is oriented for hyperconjugation in the initially formed conformation of the cation. It is argued that k(cis)/k(trans) rate ratios for substituents (Me, 8.4; Bu(t), 12.7; Ph, 3.8; NH(3)(+), 160; OH, 440) reflect their hyperconjugating ability relative to hydrogen. Faster reactions of trans isomers are observed for substitutents known (RS, N(3)) or suspected (EtSO, EtSO(2)) of stabilizing the cation by a π or σ neighboring group effect. The good Taft correlation is taken to indicate that cis substuents are reacting normally, differentiated only by their inductive effects. The slower reactions of the trans isomers are the judged to be "abnormal". This is confirmed by comparing effects of cis and trans β-OH substituents on the reactivities of dihydro phenols, naphthols, and phenanthrols. Whereas k(H)/k(OH) for cis substituents varies by less than 8-fold and is consistent with the influence of an inductive effect of the OH group (k(H)/k(OH) ≈ 2000), k(H)/k(OH) for the trans substituents varies by 3 orders of magnitude, reflecting the additional influence of the lesser hyperconjugating ability of a C-OH bond compared to a C-H bond. The magnitude and variation of this difference is consistent with C-H hyperconjugation conferring aromatic character on the arenium ions.     

Excimer Formation in a Confined Space: Photophysics of Ladderphanes with Tetraarylethylene Linkers

Communication between chromophores is vital for both natural and non‐natural photophysical processes. Spatial confinements offer unique conditions to scrutinize such interactions. Polynorbornene‐ and polycyclobutene‐based ladderphanes are ideal model compounds in which all tetraarylethylene (TAE) linkers are aligned coherently. The spans for each of the monomeric units in these ladderphanes are 4.5–5.5 Å. Monomers do not exhibit emission, because bond rotation in TAE can quench the excited‐state energy. However, polymers emit at 493 nm (Φ=0.015) with large Stokes shift under ambient conditions and exhibit dual emission at 450 and 493 nm at 150 K. When the temperature is lowered, the emission intensity at 450 nm increases, whereas that at 493 nm decreases. At 100 K, both monomers and polymers emit only at 450 nm. This shorter‐wavelength emission arises from the intrinsic emission of TAE chromophore, and the emission at 493 nm could be attributed to the excimer emission in the confined space of ladderphanes. The fast kinetics suggest diffusion‐controlled formation of the excimer.     

Enantiospecific synthesis of tricyclo[5.2.1.0]decanes via acid catalysed rearrangement of isotwistanes

An acid catalysed rearrangement was employed for the enantiospecific conversion of isotwistanol to tricyclo[5.2.1.0^4,8]decanes, which provided support for the proposed biosynthesis of allopupukeananes from pupukeananes. The strategy has been further extended to the enantiospecific synthesis of a homobrexane.     

Phosphomolybdic acid supported on silica gel: a mild, efficient and reusable catalyst for the synthesis of 2,3-unsaturated glycopyranosides by Ferrier rearrangement

A simple, mild, efficient and environmentally benign method for the synthesis of 2,3-unsaturated allyl C-glycosides and O- and S-glycosides is described using phosphomolybdic acid supported on silica gel as a reusable catalyst with high α-selectivity.     

A Stability Indicating LC Method for Deferasirox in Bulk Drugs and Pharmaceutical Dosage Forms

A novel, sensitive, stability indicating RP-LC method has been developed for the quantitative determination of deferasirox, its related impurities in both bulk drugs and pharmaceutical dosage forms. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination delivered in an isocratic mode and quantitation was by ultraviolet detection at 245 nm. The mobile phase consisted of buffer, acetonitrile and methanol (50:45:5, v/v) delivered at a flow rate of 1.0 mL min^?1. Buffer consisted of 10 mM potassium dihydrogen orthophosphate monohydrate, pH adjusted to 3.0 by using orthophosphoric acid. In the developed LC method the resolution (R _s ) between deferasirox and its four potential impurities was found to be greater than 2.0. Regression analysis showed an r value (correlation coefficient) greater than 0.999 for deferasirox and its four impurities. This method was capable to detect all four impurities of deferasirox at a level of 0.002% with respect to test concentration of 0.5 mg mL^?1 for a 10 μL injection volume. The inter- and intra-day precision values for all four impurities and for deferasirox was found to be within 2.0% RSD. The method showed good and consistent recoveries for deferasirox in bulk drugs (98.3–101.1%), pharmaceutical dosage forms (100.2–103.1%) and for its all the four impurities (99.7–102.1%). The test solution was found to be stable in methanol for 48 h. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in acid stress hydrolysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.95%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.