Lobna A. E. Nassr

Metal based pharmacologically active agents: Synthesis, structural characterization, molecular modeling, CT-DNA binding studies and in vitro antimicrobial screening of iron(II) bromosalicylidene amino acid chelates

In recent years, great interest has been focused on Fe(II) Schiff base amino acid complexes as cytotoxic and antitumor drugs. Thus a series of new iron(II) complexes based on Schiff bases amino acids ligands have been designed and synthesized from condensation of 5-bromosalicylaldehyde (bs) and α-amino acids (L-alanine (ala), L-phenylalanine (phala), L-aspartic acid (aspa), L-histidine (his) and L-arginine (arg)). The structure of the investigated iron(II) complexes was elucidated using elemental analyses, infrared, ultraviolet-visible, thermogravimetric analysis, as well as conductivity and magnetic susceptibility measurements. Moreover, the stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically. The results suggest that 5-bromosalicylaldehyde amino acid Schiff bases (bs:aa) behave as dibasic tridentate ONO ligands and coordinate to Fe(II) in octahedral geometry according to the general formula [Fe(bs:aa)2]·nH2O. The conductivity values between 37 and 64 ohm(-1) mol(-1) cm(2) in ethanol imply the presence of nonelectrolyte species. The structure of the complexes was validated using quantum mechanics calculations based on accurate DFT methods. Geometry optimization of the Fe-Schiff base amino acid complexes showed that all complexes had octahedral coordination. In addition, the interaction of these complexes with (CT-DNA) was investigated at pH=7.2, by using UV-vis absorption, viscosity and agarose gel electrophoresis measurements. Results indicated that the investigated complexes strongly bind to calf thymus DNA via intercalative mode and showed a different DNA binding according to the sequence: bsari>bshi>bsali>bsasi>bsphali. Moreover, the prepared compounds are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus flavus and Trichotheium rosium. The results of these studies indicated that the metal complexes exhibit a stronger antibacterial and antifungal efficiency than their corresponding Schiff base amino acid ligands.

Design, characterization, teratogenicity testing, antibacterial, antifungal and DNA interaction of few high spin Fe(II) Schiff base amino acid complexes

In this study, new Fe(II) Schiff base amino acid chelates derived from the condensation of o-hydroxynaphthaldehyde with L-alanine, L-phenylalanine, L-aspartic acid, L-histidine and L-arginine were synthesized and characterized via elemental, thermogravimetric analysis, molar conductance, IR, electronic, mass spectra and magnetic moment measurements. The stoichiometry and the stability constants of the complexes were determined spectrophotometrically. Correlation of all spectroscopic data suggested that Schiff bases ligands exhibited tridentate with ONO sites coordinating to the metal ions via protonated phenolic-OH, azomethine-N and carboxylate-O with the general formulae [Fe(HL)2]·nH2O. But in case of L-histidine, the ligand acts as tetradentate via deprotonated phenolic-OH, azomethine-N, carboxylate-O and N-imidazole ring ([FeL(H2O)2]·2H2O), where HL=mono anion and L=dianion of the ligand. The structure of the prepared complexes is suggested to be octahedral. The prepared complexes were tested for their teratogenicity on chick embryos and found to be safe until a concentration of 100 μg/egg with full embryos formation. Moreover, the interaction between CT-DNA and the investigated complexes were followed by spectrophotometric and viscosity measurements. It was found that, the prepared complexes bind to DNA via classical intercalative mode and showed a different DNA activity with the sequence: nhi>nari>nali>nasi>nphali. Furthermore, the free ligands and their complexes are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus flavus and Trichotheium rosium in order to assess their antimicrobial potential. The results show that the metal complexes are more reactive with respect to their corresponding Schiff base amino acid ligands.

Tailoring, physicochemical characterization, antibacterial and DNA binding mode studies of Cu(II) Schiff bases amino acid bioactive agents incorporating 5-bromo-2-hydroxybenzaldehyde

Five novel Cu(II) complexes derived from the condensation between 5-bromosalicylaldehyde (bs) and α-amino acids (L-alanine, l-phenylalanine, L-aspartic acid, L-histidine and L-arginine) were synthesized and characterized by their elemental analyses, thermogravimetric analysis, IR, mass and electronic spectra, conductance and magnetic measurements. Moreover, the stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically using continuous variation and molar ratio methods. The obtained results indicated that the Schiff bases of the amino acids: L-alanine, L-phenylalanine, L-histidine and L-arginine behave as tridentate ligands. The ligands are coordinating with the Cu(II) via azomethine nitrogen, deprotonated carboxylate oxygen and phenolic oxygen. However, in the case of L-aspartic, the ligand acts as tetradentate due to the coordination of the second carboxylate group. Based on the studies of magnetic moments and electronic spectra, a square planar geometry has been proposed for all Cu(II) complexes except bromsalicylaldehydine aspartate complex which has a distorted tetrahedral structure. The representative Schiff bases and their Cu(II) complexes were tested in vitro for their antibacterial activity against two Gram-positive bacteria (Micrococcus luteus and Bacillus cereus) and one Gram-negative bacteria (Pseudomonas aeruginosa). All the complexes showed activity against the organisms more than the free Schiff base ligands and the activity increases with the increase in concentration of test solution containing the new complexes. Moreover, the interaction of the prepared Schiff base amino acid Cu(II) complexes with calf thymus DNA has been investigated by absorption spectra, viscosity and gel electrophoresis measurement and the mode of CT-DNA binding to the complexes has been explored. The investigated complexes exhibit cooperative binding and presumably intercalate into DNA and follow the trend: bsarc>bshc>bsalc>bsphalc>bsasc.

Novel mechanistic aspects on the reaction between low spin Fe(II) Schiff base amino acid complexes and hydrogen peroxide-spectrophotometric tracer of intraperoxo intermediate catalyzed reaction.

The kinetics and mechanism of the reaction of hydrogen peroxide with some Fe(II) Schiff base complexes were investigated spectrophotometrically in aqueous solution at pH 8 and 35 degrees C under pseudo-first-order conditions. The used ligands were derived from salicylaldehyde or o-hydroxynaphthaldehyde and some amino acids (l-leucine, l-iso-leucine, l-serine, l-methionine and dl-tryptophan). It was found that the formation of the purple interaperoxo complex appears only above pH 7.5. The reaction consists of two steps. The first step involves reversible formation of the intraperoxo intermediate which renders irreversible at pH 8. The second step consists of inner-sphere electron transfer. The suggested scheme illustrated first-order kinetics at low [H(2)O(2)] and zero-order at high [H(2)O(2)]. Moreover, the activation parameters of the reaction were evaluated.

Initial State and Transition State Contributions to Reactivity Trends of Base-Catalyzed Hydrolysis of Some Nitro Chromen-2-One Derivatives

Abstract Base-catalyzed hydrolysis of 6-nitro-2H-chromen-2-one (NC) and 6-nitro-2H-chromen-2-one-3-carboxylic acid (NCC) in binary water/methanol and water/acetone mixtures were studied kinetically at 298 K. The changes in the activation barrier of the investigated compounds from water to water/methanol and water/acetone mixtures were estimated from the kinetic data. Solvent effects on the reactivity trends were analyzed into initial state and transition state components. These were determined from the transfer chemical potentials of the reactants and the kinetic data. The transfer chemical potentials δmμθ for NC were derived from its solubilities in water/methanol and water/acetone mixtures, and the transfer chemical potentials for NCC− anion were derived from solubility data for its calcium, cerium and lanthanum salts. Base-catalyzed hydrolysis of NC and NCC in water/methanol and water/acetone mixtures follow a rate law with kobs=k2·c(HO−) and kobs=k1+k2·c(HO−), respectively. The decrease in the rate constants of base-catalyzed hydrolysis of NC as methanol% or acetone% increases is dominated by the initial state (IS), while the decrease in the rate constants of base-catalyzed hydrolysis of NCC as methanol% or acetone% increases is dominated by the transition state (TS).

Reactivity trends in the base hydrolysis of 6-nitro-2H-chromen-2-one and 6-nitro-2H-chromen-2-one-3-carboxylic acid in binary mixtures of water with methanol and acetone at different temperatures

Kinetics of the base hydrolysis of 6-nitro-2H-chromen-2-one (NC) and 6-nitro-2H-chromen-2-one-3-carboxylic acid (NCC) in water-methanol and water-acetone mixtures was studied at temperature range from 283 to 313 K. The activation parameters of the reactions were evaluated and discussed. The change in the activation barrier of the investigated compounds from water to water-methanol and water-acetone mixtures were estimated from the kinetic data. The base hydrolysis of NC and NCC in the water-methanol and water-acetone mixtures follows a rate law with kobs = k2[OH−] and kobs = k1 + k2[OH−], respectively. The decrease in the rate constants of NC and NCC hydrolysis, as the proportion of methanol and acetone increases, is accounted for by the destabilization of the OH− ion. The activation and thermodynamic parameters were determined.

Kinetic study of the hydroxide ion attack on and DNA interaction with high spin iron(II) Schiff base amino acid chelates baering ONO donors

Kinetic study of some novel high spin Fe(II) complexes of Schiff base ligands derived from 5-bromsalicyaldehyde and amino acids with the OH− ion and DNA has been carried out. Based on the kinetic data, the rate law and a plausible mechanism were proposed. Kinetic data of the base catalyzed hydrolysis imply pseudo first-order double stage process due to the presence of mer- and fac-isomers. The observed rate constants kobs were correlated with the effect of a substituent R in the structure of ligands. The rate constants and activation parameters are in good agreement with stability constants of the studied complexes. Reactivity of the complexes towards DNA correlated well with the reported binding constants.

Hydrophilicity and acid hydrolysis of water-soluble antibacterial iron(II) Schiff base complexes in binary aqueous solvents

Kinetics of acid hydrolysis of seven antibacterial iron(II) Schiff base complexes has been studied. The Schiff base ligands were derived from sodium 2-hydroxybenzaldehyde-5-sulfonate and a series of amino acids. The hydrolysis rate is studied by spectrophotometric method and compared with complex hydrophilicity. Addition of the organic co-solvent, dimethylsulfoxide or n-propanol, significantly accelerates the hydrolysis.

Kinetic investigation of hydroxide ion attack at high spin Fe(II) bromosalicylidine chelates with amino acids in binary aqueous solvents: Initial and transition state analysis

We have investigated the kinetics of hydroxide ion attack at iron(II) chelates with 5-bromosalicylidene derivatives of amino acids (alanine, phenylalanine, aspartic acid, histidine, and arginine) in binary aqueous mixed solvents at 298 K. The observed reactivity trends are discussed in connection with the complexes hydrophobicity/hydrophilicity, transfer chemical potentials of hydroxide ion and the complex, and the solvent effects.

Kinetic study and reactivity trends of hydroxide ion attack on some chromen-2-one laser dyes in binary water-methanol and water-acetone mixtures

The kinetics of base-catalyzed hydrolysis of 7-dimethylamino-4-methyl-2H-chromen-2-one (DMAC) and 7-diethylamino-4-methyl-2H-chromen-2-one (DEAC) in binary water-methanol and water-acetone mixtures were studied in the temperature range from 288 to 313 K. The activation and thermodynamic parameters of these reactions were evaluated and discussed. The change in the activation energy in going from water to aqueous methanol and aqueous acetone was estimated from the kinetic data. Base-catalyzed hydrolysis of DMAC) and DEAC in aqueous methanol and aqueous acetone follows the first-order kinetic law with respect to hydroxide ion, kobs= k2[OH]. The hydrolysis rate constants of DMAC and DEAC decrease as the fraction of methanol or acetone in the binary mixture rises, which is due to destabilization of OH− ion. The high negative entropies of activation support the proposed mechanism involving formation of an intermediate complex and reflect rigidity and stability of the latter. Opening of the pyran ring in the intermediate complex is the rate-determining step.