Schiff base of gossypol with 3,6,9-trioxa-decylamine complexes with monovalent cations studied by mass spectrometry, (1)H-NMR, FTIR, and PM5 semiempirical methods

A new Schiff base of gossypol with 3,6,9-trioxo-decylamine (GSTB) forms stable complexes with monovalent cations. This process of complex formation was studied by electrospray ionization mass spectrometry, (1)H-NMR and FTIR spectroscopy, and the PM5 (parametric method 5) semiempirical method. It is found that GSTB forms 1 : 1 and 1 : 2 complexes with Li(+) and Na(+) and 1 : 1 complexes with K(+), Rb(+), or Cs(+) cations and exists in all these complexes in the enamine-enamine tautomeric form. Moreover, within these complexes only Li(+) cations can fluctuate between the oxygen atoms of trioxo-alkyl chains. All other cations are strongly localized. In the complex of GSTB with two protons localized on the N atoms of the Schiff base, the imine-imine tautomeric form is realized. The complexes of the Schiff base with K(+), Rb(+), or Cs(+) cations are the 1 : 1 type with the oxygen atoms of the trioxo-alkyl chains, as well as the O(1)H or O(1')H group coordinating the cation. The structures of the complexes are calculated by the PM5 semiempirical method and discussed.     

Multinuclear magnetic resonance, electrospray ionization-mass spectroscopy, and parametric method 5 studies of a new derivative of gossypol with 2-thiophenecarbohydrazide as well as its complexes with LI+, Na+, K+, RB+, and Cs+ cations

A new derivative of racemic gossypol with 2-thiophenecarbohydrazide (GHHT) and its complexes with monovalent cations have been synthesized and studied by electrospray ionization-mass spectroscopy (ESI-MS), multinuclear nuclear magnetic resonance (NMR), as well as by the Parametric Method 5 (PM5) methods. It is demonstrated that GHHT forms stable complexes of 1:1 stoichiometry with monovalent metal cations. The structures of the complexes are stabilized by three types of intramolecular hydrogen bonds. The spectroscopic methods have provided clear evidence that GHHT and its complexes exist in the DMSO-d6 solution in the N-imine-N-imine tautomeric forms. The structures of the GHHT and its complexes with Li+, Na+, K+, Rb+, and Cs+ cations are visualized and discussed in detail.     

Monensin A methyl ester complexes with Li+, Na+, and K+ cations studied by ESI-MS, 1H- and 13C-NMR, FTIR, as well as PM5 semiempirical method

Monensin A methyl ester (MON1) was synthesized by a new method and its ability to form complexes with Li+, Na+, and K+ cations was studied by electrospray ionization-mass spectroscopy (ESI-MS), 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), and PM5 semiempirical methods. It is shown that MON1 with monovalent metal cations forms stable complexes of 1:1 stoichiometry. The structures of the complexes are stabilized by intramolecular hydrogen bonds in which the OH groups are always involved. In the structure of MON1, the oxygen atom of the C=O ester group is involved in very weak bifurcated intramolecular hydrogen bonds with two hydroxyl groups, whereas in the complexes of MON1 with monovalent metal cations the C=O ester group is not engaged in any intramolecular hydrogen bonds. Furthermore, it is demonstrated that the strongest intramolecular hydrogen bonds are formed within the MON1-Li+ complex structure. The structures of the MON1 and its complexes with Li+, Na+, and K+ cations are visualized and discussed in detail.     

1H- and 13C-NMR, FTIR, UV-VIS, ESI-MS, and PM5 studies as well as emission properties of a new Schiff base of gossypol with 5-methoxytryptamine and a new hydrazone of gossypol with dansylhydrazine

A new Schiff base of gossypol with 5-methoxytryptamine (GSTR) and a new hydrazone of gossypol with dansylhydrazine (GHDH) have been synthesized and studied by Fourier transform infrared (FTIR), 1H and 13C nuclear magnetic resonance (NMR), ultraviolet-visible (UV-VIS), electrospray ionization-mass spectroscopy (ESI-MS) as well as the parametric method PM5. The spectroscopic methods have provided clear evidence that GSTR exists in chloroform solution as an enamine-enamine tautomer, whereas GHDH is present in chloroform as a N-imine-N-imine tautomer. The fluorescence spectra of both compounds indicate that their quantum yield of fluorescence is increased by one or two orders of magnitude compared to that of pure gossypol. The ESI-MS spectra of the 1:1 mixtures of GSTR or GHDH with formic acid have demonstrated that both compounds exist as protonated monomers in the gas phase, whereas GHDH can also exist in a stable protonated dimeric structure. The structures of the stable tautomers are calculated and visualized using the PM5 semiempirical method. The intra- and intermolecular hydrogen bonds within these structures are discussed.     

Spectroscopic studies and PM5 semiempirical calculations of new Schiff bases of gossypol with polyoxaalkylamines

Three Schiff bases of racemic gossypol with polyoxaalkylamines were synthesized and studied by FTIR and (1)H-NMR spectroscopy, and their structures were calculated by the PM5 semiempirical method. These Schiff bases exist in the solid state and in solutions as enamine forms. An increasing length of the polyoxaalkyl chain causes the increase of the interaction of the oxygen atoms of this chain with the OH groups in the 6,6' positions. This interaction is very well evidenced in the FTIR and (1)H-NMR spectra. The structures of the Schiff bases and the hydrogen bonds within these structures are discussed.     

Spectroscopic studies and PM3 semiempirical calculations of Schiff bases of gossypol with L-amino acid methyl esters

Three Schiff bases of racemic gossypol with L-amino acid methyl esters are synthesized and studied by FTIR and (1)H-NMR spectroscopy, and their structures are calculated by the PM3 semiempirical method. The Schiff bases in the study exist in the solid state and in solutions as enamine forms. The existence of diastereoisomers is very visible in the (1)H-NMR spectra. The amount of the diastereoisomers depends on the amount of time the solutions are rested in diffused light. The epimerization from D,L-isomer to L,L-isomer is very slow. The structures of the Schiff bases and the hydrogen bonds within these structures are discussed.     

Spectroscopic, mass spectrometry, and semiempirical investigation of a new ester of Monensin A with ethylene glycol and its complexes with monovalent metal cations

A new ester of Monensin A with ethylene glycol (MON2) has been synthesized by a new method and its ability to form complexes with Li+, Na+, and K+ cations has been studied by ESI MS, 1H and 13C NMR, FT-IR, and PM5 semiempirical methods. It is demonstrated that MON2 forms stable complexes of 1:1 stoichiometry with monovalent metal cations. The structures of the complexes are stabilized by intramolecular hydrogen bonds in which the OH groups are always involved. In the structure of MON2 the oxygen atom of the C=O ester group is involved in very weak bifurcated intramolecular hydrogen bonds with two hydroxyl groups, whereas in the complexes of MON2 with monovalent metal cations the C=O ester group is not engaged in any intramolecular hydrogen bonds. The structures of the MON2 and its complexes with Li+, Na+, and K+ cations are visualized and discussed in detail.     

7Li-NMR and FTIR studies of lithium, potassium, rubidium, and cesium complexes with ionophore lasalocid in solution

Lasalocid metal salts were combined with 1 : 1 lithium and 2:2 potassium, rubidium, and cesium to form complexes. The nature of the lasolocid salt complexes was studied in a solid and chloroform by FTIR spectroscopy in the middle and far IR regions. The process of the complexation of lithium was also studied by (7)Li-NMR. In chloroform a 1 : 1 complex of lasalocid and Li(+) ions was formed. Continuous absorption was observed in the far FTIR spectrum of this complex. It indicated large Li(+) polarizability, which was due to fast fluctuations of the Li(+) ions in the multiminima potentials, in the monomeric structure. In the lasalocid salt with the other monovalent cations (K(+), Rb(+), Cs(+)) 2:2 complexes were formed in which the cations showed cation polarizability, which strongly depended on the mass and the radius of the cations.     

Multinuclear NMR and FTIR studies of new polyoxaalkyl esters of lasalocid and their complexes with lithium and sodium cations

Three new polyoxaalkyl esters of lasalocid are synthesized. Their ability to form complexes with Li(+) and Na(+) cations is studied using multinuclear NMR methods, FTIR spectroscopy in the middle and far IR regions, and mass spectrometry. It is found that lasalocid esters form only 1:1 complexes with the metal cations. The results of the NMR study in pyridine show that the polyoxaalkyl chain of the ester does not influence the complex formation of the lasalocid part of the esters. The reason for this is the competition of the pyridine molecules in the complexation process of metal cations. In chloroform the properties of the complex formation have changed and the oxaalkyl chain plays an important role within the complexation process, as demonstrated by the dependence of the respective continuous absorptions in the far IR region on the length of the oxaalkyl chain (i.e., on the number of the oxygen atoms in the chain). The modifications of the lasalocid molecule influences the complexation of the metal cation and probably the interactions with the membrane. An increase in antibiotic activity is found as a consequence of these changed interactions.     

Synthesis, characterization and X-ray crystal structures of dinuclear nickel(II) complexes of a novel potentially hexadentate but functionally tetradentate binucleating ligand

A binucleating potentially hexadentate chelating agent containing oxygen, nitrogen and sulfur as potential donor atoms (H₂ONNO) has been synthesized by condensing α,α-xylenebis(N-methyldithiocarbazate) with 2,4-pentanedione. An X-ray crystallographic structure determination shows that the Schiff base remains in its ketoimine tautomeric form with the protons attached to the imine nitrogen atoms. The reaction of the Schiff base with nickel(II) acetate in a 1:1 stoichiometry leads to the formation of a dinuclear nickel(II) complex [Ni(ONNO)]₂ (ONNO²⁻ = dianionic form of the Schiff base) containing N,O-chelated tetradentate ligands, the sulfur donors remaining uncoordinated. A single crystal X-ray structure determination of this dimer reveals that each ligand binds two low spin nickel(II) ions, bridged by a xylyl group. The nickel(II) atoms adopt a distorted square-planar geometry in a trans-N₂O₂ donor environment. Reaction of the Schiff base with nickel(II) acetate in the presence of excess pyridine leads to the formation of a similar dinuclear complex, [Ni(ONNO)(py)]₂, but in this case comprises five coordinate high-spin Ni(II) ions with pyridine ligands occupying the axial coordination sites as revealed by X-ray crystallographic analysis.     

Membrane actions of male contraceptive gossypol tautomers

The role of different gossypol tautomers in the interaction of this molecule with membranes has been investigated using the isolated hemiacetal moiety of gossypol and the pH dependency of the keto-enol tautomeric equilibrium. Our results indicate that: the actions of the hemiacetal tautomer cannot explain the effects of gossypol on mitochondrial oxidative phosphorylation, lipid membrane interfacial potentials, and proton conductance of lipid bilayers; the enolate forms of gossypol are the species that bind to the membrane interface and decrease the electrostatic interfacial potential; and the uncharged (keto and/or enol) species in equilibrium with the enolate forms of gossypol give the molecule the ability to carry protons across biological membranes.     

Interaction of gossypol with amino acids and peptides as a model of enzyme inhibition

In order to clarify the interaction of gossypol with proteins, the pure diastereoisomeric Schiff bases from L-tryptophan methyl ester and both gossypol enantiomers were prepared. Their c.d. and n.m.r. spectra demonstrate that the interaction between gossypol and tryptophan, previously reported to involve a weakly associated complex, consists in Schiff base formation. Recent studies on enzyme inhibition by gossypol are discussed; it is suggested that nonspecific covalent binding of gossypol to proteins may be responsible for a significant proportion of the in vitro effects of gossypol.     

Surprising roles of electrostatic interactions in DNA-ligand complexes

The positions of cations in x-ray structures are modulated by sequence, conformation, and ligand interactions. The goal here is to use x-ray diffraction to help resolve structural and thermodynamic roles of specifically localized cations in DNA-anthracycline complexes. We describe a 1.34 A resolution structure of a CGATCG(2)-adriamycin(2) complex obtained from crystals grown in the presence of thallium (I) ions. Tl(+) can substitute for biological monovalent cations, but is readily detected by distinctive x-ray scattering, obviating analysis of subtle differences in coordination geometry and x-ray scattering of water, sodium, potassium, and ammonium. Six localized Tl(+) sites are observable adjacent to each CGATCG(2)-adriamycin(2) complex. Each of these localized monovalent cations are found within the G-tract major groove of the intercalated DNA-drug complex. Adriamycin appears to be designed by nature to interact favorably with the electrostatic landscape of DNA, and to conserve the distribution of localized cationic charge. Localized inorganic cations in the major groove are conserved upon binding of adriamycin. In the minor groove, inorganic cations are substituted by a cationic functional group of adriamycin. This partitioning of cationic charge by adriamycin into the major groove of CG base pairs and the minor groove of AT base pairs may be a general feature of sequence-specific DNA-small molecule interactions and a potentially useful important factor in ligand design.     

Structure-activity relationships among noncyclic dicarboxamide Li(+)-selective carriers studied in lipid bilayer membranes.

The structure-activity relationships among three noncyclic diimide ionophores, designed to be Li+ carriers, were studied in lipid bilayer membranes. These ionophores (ETH1644, ETH1810, and ETH1811) vary in their N-imide substituents, going from two isobutyls to one isobutyl and one cyclohexyl to two cyclohexyls, respectively. ETH1811 was found to form two types of complexes with 1:1 and 1:2 ion-carrier stoichiometries, the former type dominant over most of the ionophore (0.1-10 microM) and salt (0.01-1.0 M) concentration ranges studied. In contrast, ETH1644 and ETH1810 were previously found to form a single type of complex with the 1:2 stoichiometry. The alkali cations selectivity sequence induced by ETH1811 is Li+ (1) greater than Na+ (0.08) greater than K+ (0.02) greater than Cs+ (0.008). These ETH1811-induced ionic selectivites as well as its relative potency in ion transport were found to be inferior to those of ETH1644 and ETH1810 (the latter being the best in this series). The conductance-voltage relationships reported here, for all three ionophores transporting alkali cations, were found to fit with a transport mechanism in which the diffusion of the ion-ionophore complex across the membrane is the single rate-limiting step, with the following exceptions: The addition of the dissociation of the ion-carrier complex as a second rate limiting step, for the Li(+)-ETH1810 and the Li(+)-ETH1811 systems. For ETH1810 the kinetics of the dissociation step is a minor, whereas for ETH1811 case it is a significant, addition (the ratio of the diffusion to dissociation rate constants being 0.08 and 0.2, respectively). The implications of the effects of the continuous structural change of these ionophores on their performance as ion carriers and on the design and synthesis of improved Li(+)-selective ionophores are discussed.     

Cd(II) and Cu(II) complexes of polydentate Schiff base ligands: synthesis, characterization, properties and biological activity

We report the synthesis of the Schiff base ligands, 4-[(4-bromo-phenylimino)-methyl]-benzene-1,2,3-triol (A₁), 4-[(3,5-di-tert-butyl-4-hydroxy-phenylimino)-methyl]-benzene-1,2,3-triol (A₂), 3-(p-tolylimino-methyl)-benzene-1,2-diol (A₃), 3-[(4-bromo-phenylimino)-methyl]-benzene-1,2-diol (A₄), and 4-[(3,5-di-tert-butyl-4-hydroxy-phenylimino)-methyl]-benzene-1,3-diol (A₅), and their Cd(II) and Cu(II) metal complexes, stability constants and potentiometric studies. The structure of the ligands and their complexes was investigated using elemental analysis, FT-IR, UV-Vis, ¹H and ¹³C NMR, mass spectra, magnetic susceptibility and conductance measurements. In the complexes, all the ligands behave as bidentate ligands, the oxygen in the ortho position and azomethine nitrogen atoms of the ligands coordinate to the metal ions. The keto-enol tautomeric forms of the Schiff base ligands A₁-A₅ have been investigated in polar and non-polar organic solvents. Antimicrobial activity of the ligands and metal complexes were tested using the disc diffusion method and the strains Bacillus megaterium and Candida tropicalis.Protonation constants of the triol and diol Schiff bases and stability constants of their Cu²⁺ and Cd²⁺ complexes were determined by potentiometric titration method in 50% DMSO-water media at 25.00 ± 0.02 °C under nitrogen atmosphere and ionic strength of 0.1 M sodium perchlorate. It has been observed that all the Schiff base ligands titrated here have two protonation constants. The variation of protonation constant of these compounds was interpreted on the basis of structural effects associated with the substituents. The divalent metal ions of Cu²⁺ and Cd²⁺ form stable 1:2 complexes with Schiff bases.The Schiff base complexes of cadmium inhibit the intense chemiluminescence reaction in dimethylsulfoxide (DMSO) solution between luminol and dioxygen in the presence of a strong base. This effect is significantly correlated with the stability constants K_CdL of the complexes and the protonation constants K_OH of the ligands; it also has a nonsignificant association with antibacterial activity.     

Ni(II) complexes with Schiff bases derived from amino sugars

It was found by 1H and 13C NMR spectroscopy that the Schiff base, 2-deoxy-2-(2-hydroxybenzaldimino)-D-glucopyranose exhibits enol-imine-keto-amine and anomeric equilibria in methanolic, and in dimethyl sulfoxide solutions. The reaction of the Schiff base with nickel acetate gave the bidentate, mononuclear Ni(II) complex that was characterized by spectroscopic methods and by cyclic voltammetry. The coordination of the Schiff base to the metal is through the enol-imine tautomeric form, and the anomeric equilibrium remains in dimethyl sulfoxide solutions. This complex was also obtained by reaction of D-glucosamine with Ni(II) salicylaldehydate. The same reaction was employed for the synthesis of bis-N-[2-deoxy-D-galactopyranosyl-2-(2-hydroxybenzaldiminate)]Ni(II). The small paramagnetic shifts of the 1H NMR resonances of the complexes suggest that paramagnetic species are present in low proportions.     

Spectroscopic analysis of recombinant rat histidine decarboxylase

Mammalian histidine decarboxylases have not been characterized well owing to their low amounts in tissues and instability. We describe here the first spectroscopic characterization of a mammalian histidine decarboxylase, i.e. a recombinant version of the rat enzyme purified from transformed Escherichia coli cultures, with similar kinetic constants to those reported for mammalian histidine decarboxylases purified from native sources. We analyzed the absorption, fluorescence and circular dichroism spectra of the enzyme and its complexes with the substrate and substrate analogues. The pyridoxal-5'-phosphate-enzyme internal Schiff base is mainly in an enolimine tautomeric form, suggesting an apolar environment around the coenzyme. Michaelis complex formation leads to a polarized, ketoenamine form of the Schiff base. After transaldimination, the coenzyme-substrate Schiff base exists mainly as an unprotonated aldimine, like that observed for dopa decarboxylase. However, the coenzyme-substrate Schiff base suffers greater torsion than that observed in other L-amino acid decarboxylases, which may explain the relatively low catalytic efficiency of this enzyme. The active center is more resistant to the formation of substituted aldamines than the prokaryotic homologous enzyme and other L-amino acid decarboxylases. Characterization of the similarities and differences of mammalian histidine decarboxylase with respect to other homologous enzymes would open new perspectives for the development of new and more specific inhibitors with pharmacological potential.     

Structural, spectroscopic and semiempirical characterisation of the calcium cation complexes with 14-membered macrocyclic ligand of cyclic oxaalkyl diamide of o-phthalic acid

Cyclic oxaalkyl diamide of o-phthalic acid (CPhDA) has been obtained and its ability to form complexes with calcium cation has been studied by X-ray, ESI MS, ¹H and ¹³C NMR, FT-IR and PM5 semiempirical methods. The ESI MS measurements have proved that in gas phase the 3:1, 2:1 and 1:1 CPhDA-Ca²⁺ as well as 3:1 and 2:1 CPhDA-Ca(ClO₄)⁺ complexes are formed. In the solid state a 3:1 complex between CPhDA and calcium perchlorate of the CPhDA-Ca(ClO₄)₂-H₂O (3:1:0.5) stoichiometry crystallises as hemihydrate in centrosymmetric space group (R-3) of the rhombohedral system. In crystal, the central Ca²⁺ cation is coordinated by the three CPhDA ligands via the carbonyl oxygen atoms in a distorted trigonal antiprism. The cationic [Ca(CPhDA)₃]²⁺ complex exhibits a threefold symmetry. Two [Ca(CPhDA)₃]²⁺ cations related by an inversion centre interact with oxygen atom of water molecule that statistically occupies two positions around the inversion centre along the Ca···Ca axis. The FT-IR spectra show the characteristic changes in the frequencies of the amide I and amide II bands upon complexation. The structures of the CPhDA and its complexes with calcium cation are visualised using DFT and PM5 methods and discussed in detail.     

Effect of carboxylate and Na ions on the tautomeric status of 9-methylguanine

Interactions of 9-methylguanine (m9Gua) with carboxylate ion of acetic acid (CH3COO-) and Na+ were studied by 1H NMR spectroscopy and ab initio quantum chemical calculations of the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels of theory. Changes in the m9Gua 1H NMR spectrum in the presence of the equimolar amount of sodium acetate (NaAc), which in anhydrous DMSO dissociates to CH3COO- and Na+, were interpreted as a consequence of a complex formation of m9Gua in the amino-keto-N1H tautomeric form (m9GuaN1H) with carboxylate ions via two H-bonds involving amino and N1H-imino protons. Quantum chemical calculations of interactions of the m9GuaN1H ground-state tautomer and the m9GuaN3H high energy one with relative energy 20.01 kcal/mol show that the ground state tautomer forms the ground-state complex CH3COO-:mgGuaN1H, by 5.57 kcal/mol more stable than the CH3COO-:m9GuaN3H complex, and coordination of Na+ with the O6 and N7 atoms reduces this energy difference to 2.57 kcal/mol. Such a coordination of Na+ with tautomer m9GuaN3H therewith decreases its relative energy only to 13.31 kcal/mol. Non-additivity of the two ligands contributions to the 8-times reduction of the relative energy of the high energy tautomer in the CH3COO-:m9GuaN3H:Na+(O6,N7) triple complex was concluded, the role of CH3COO- being dominant. Besides, coordination with Na+ resulted in an iminoproton transfer from the base to CH3COO- in the triple complexes of both tautomers, according to calculations in vacuum. Biological significance of the results is noticed.     

Antimicrobial, spectral, magnetic and thermal studies of Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes of the Schiff base derived from oxalylhydrazide

The Schiff base ligand, oxalic bis[(2-hydroxybenzylidene)hydrazide], H(2)L, and its Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes were prepared and tested as antibacterial agents. The Schiff base acts as a dibasic tetra- or hexadentate ligand with metal cations in molar ratio 1:1 or 2:1 (M:L) to yield either mono- or binuclear complexes, respectively. The ligand and its metal complexes were characterized by elemental analyses, IR, (1)H NMR, Mass, and UV-Visible spectra and the magnetic moments and electrical conductance of the complexes were also determined. For binuclear complexes, the magnetic moments are quite low compared to the calculated value for two metal ions complexes and this shows antiferromagnetic interactions between the two adjacent metal ions. The ligand and its metal complexes were tested against a Gram + ve bacteria (Staphylococcus aureus), a Gram -ve bacteria (Escherichia coli), and a fungi (Candida albicans). The tested compounds exhibited high antibacterial activities.