The influence of halogens on the electronic system of biologically important ligands: spectroscopic study of halogenobenzoic acids, halogenobenzoates and 5-halogenouracils

Halogenobenzoates and 5-halogenouracils are commonly applied in industrial and medical fields. From this point of view, it is very important to study the effect of halogens and metal on the above mentioned biologically important ligands. This paper reviews the results of many years’ studies on the influence of halogens (in the series: F → Cl → Br → I) on the electronic system of benzoic acid and uracil. Moreover, the effect of metals (in the series: Mg → Ca → Sr → Ba ; Li → Na → K; in the long series of lanthanide elements: La(III) → Lu(III) except Pm) on the electronic charge distribution in halogenobenzoates is discussed. Systematic changes in the spectra of studied compounds were found. It allowed us to say that ionic potential and electronegativity of elements are the main parameters deciding on the electronic charge distribution in the molecule. Different complementary spectroscopic and quantum-chemical methods were applied in the study.     

Molecular and cellular mechanism of the effect of La(III) on horseradish peroxidase

Horseradish is an important economic crop. It contains horseradish peroxidase (HRP) and lots of nutrients, and has specific pungency. Lanthanum is one of the heavy metals in the environment. It can transfer through the food chain to humans. In this paper, the molecular and cellular mechanism of the toxic effects of La(III) on HRP in vivo was investigated with an optimized combination of biophysical, biochemical, and cytobiological methods. It was found that La(III) could interact with O and/or N atoms in the backbone/side chains of the HRP molecule in the cell membrane of horseradish treated with 80 μM La(III), leading to the formation of a new complex of La and HRP (La–HRP). The formation of the La–HRP complex causes the redistribution of the electron densities of atoms in the HRP molecule, especially the decrease in the electron density of the active center, Fe(III), in the heme group of the La–HRP molecule compared with the native HRP molecule in vivo. Therefore, the electron transfer and the activity of HRP in horseradish treated with 80 μM La(III) are obviously decreased compared with those of the native HRP in vivo. This is a possible molecular and cellular mechanism for the toxic effect of La(III) on HRP in vivo. It is suggested that the accumulation of La in the environment, especially the formation of the La–HRP complex in vivo, is harmful to organisms.     

Thiophenic compounds adsorption on Na(I)Y and rare earth exchanged Y zeolites: a density functional theory study

We have theoretically investigated the adsorption of thiophene, benzothiophene, dibenzothiophene on Na(I)Y and rare earth exchanged La(III)Y, Ce(III)Y, Pr(III)Y Nd(III)Y zeolites by density functional theory calculations. The calculated results show that except benzothiophene adsorbed on Na(I)Y with a stand configuration, the stable adsorption structures of other thiophenic compounds on zeolites exhibit lying configurations. Adsorption energies of thiophenic compounds on the Na(I)Y are very low, and decrease with the increase of the number of benzene rings in thiophenic compounds. All rare earth exchanged zeolites exhibit strong interaction with thiophene. La(III)Y and Nd(III)Y zeolites are found to show enhanced adsorption energies to benzothiophene and Pr(III)Y zeolites are favorable for dibenzothiophene adsorption. The analysis of the electronic total charge density and electron orbital overlaps show that the thiophenic compounds interact with zeolites by π-electrons of thiophene ring and exchanged metal atom. Mulliken charge populations analysis reveals that adsorption energies are strongly dependent on the charge transfer of thiophenic molecule and exchanged metal atom.     

Synthesis, characterization and biological activity evaluation of Pt(II), Pd(II), Co(III) and Ni(II) complexes with N-heteroaromatic selenosemicarbazones

Five new complexes of Pt(II), Pd(II), Co(III) and Ni(II) with 2-pyridine(quinoline)carboxaldehyde selenosemicarbazones were synthesized and characterized. Crystal structures of Pt(II) complex with the pyridine derivative and Co(III) complex with the quinoline derivative were determined. In all complexes the ligands were coordinated through N₂Se donor atom set forming either square-planar (Pt, Pd) or octahedral (Co, Ni) geometry. All complexes showed biological activity.     

Coordination polymers of Ln(III): Synthesis, characterization, catalytic and antimicrobial aspects

Coordination polymers of HEAP-ED with La(III), Pr(III), Nd(III), Sm(III), Gd(III), Tb(III) and Dy(III) metal ions have been synthesized and characterized by elemental analyses, electronic spectra, magnetic susceptibilities, FTIR, NMR, scanning electronic microscopy (SEM) and thermogravimetric analyses. Catalytic activity of selected coordination polymers was examined for pharmaceutical important organic synthesis. Antimicrobial activity of isolated Ln(III) coordination polymers against Escherichia coli, Bacillus subtilis, Staphylococcus aureus (bacteria) and Saccharomyces cerevisiae (yeast) were measured. It was observed from the study that the Ln(III) coordination polymers acted as an efficient and effective catalysts and antimicrobial agents.     

Enzymatic synthesis of isoniazid in non-aqueous medium

The reaction of ethyl isonicotinate (ethyl 4-pyridine carboxylate) with hydrazine hydrate as a nucleophile was conducted in 1,4-dioxane as a solvent to produce 4-pyridine carboxylic acid hydrazide (isoniazid) with different immobilized lipases. Isoniazid is an important agent in the treatment of tuberculosis and it can be synthesized via Novozym 435 as the catalyst. Equimolar quantities of reactants (3.33 × 10⁻⁴ mol/cm³ each) in 30 mL solution with 1.67 × 10⁻³ g/cm³ Novozym 435 leads to 52% conversion in 24 h. Based on the initial rate studies and concentration profiles (progress curve) analysis, a complete rate equation is proposed taking into account the irreversible inactivation caused by ethyl isonicotinate at very high concentrations. The kinetic model follows the ternary complex mechanism with dead end inhibition by ethyl isonicotinate.     

Synthesis, characterization and biological activity of complexes of lanthanum(III) with 2-(1'-phenyl- 2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline and 2-(1'-p-phenol-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline

Two novel ligands 2-(1'-phenyl-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline (L1) and 2-(1'-p-phenol-2'-carboxyl-3'-aza-butyl)-1,10-phenanthroline (L2), and their La(III) complexes of La(III)L1, La(III)(L1)(2), La(III)L2, and La(III)(L2)(2), were synthesized and characterized by (1)H NMR, elemental analysis, IR, thermal analysis and conductance measurement. All complexes have been assayed for anticancer activity in vitro against HL-60 (human leukocytoma) cells, PC-3MIE8 (human prostate carcinoma) cells, BGC-823 (human stomach carcinoma) cells, MDA-MB-435 (human galactophore carcinoma) cells, Bel-7402 (human liver carcinoma) cells, and HeLa (human cervix carcinoma) cells. Results showed that the two complexes La(III)L1 and La(III)(L1)(2) exhibited good cytotoxic activity against different cell lines in general; and La(III)(L1)(2) is more effective than cisplatin against all six cell lines. DNA-binding studies indicated that, besides the intercalation, the complexes bind to DNA by the other interaction(s).     

Solution and solid-state structures of lanthanide nitrate complexes with [(MeO)2P(O)]2C(OH)R (R=Me,tBu)

The complexes Ln(NO₃)₃L^a ₂ (L^a=[(MeO)₂P(O)]₂C(OH)Me; Ln=La–Er) and Ln(NO₃)₃L^b ₂ (L^b=[(MeO)₂P(O)]₂C(OH)^tBu); Ln=La–Lu) have been synthesised. The solid-state structures examined by IR spectroscopy, single crystal X-ray diffraction and extended X-ray absorption fine structure show uniformity across the series up to Dy, the metal being ten coordinate. Solution structures have been examined by ³¹P NMR spectroscopy, conductivity, electrospray mass spectrometry and EXAFS, and results indicate that solution structures fall into two groups, one for the lighter (La–Sm) and one for the heavier (Eu–Lu) lanthanides. This structural change involves the diphosphonate ligands, which appear to be monodenate for the heavier metals, affording these a coordination number of eight.     

Synthesis and luminescence properties of polymer–rare earth complexes containing salicylaldehyde‐type bidentate Schiff base ligand

Using molecular design and polymer reactions, two types of bidentate Schiff base ligands, salicylaldehyde–aniline (SAN) and salicylaldehyde–cyclohexylamine (SCA), were synchronously synthesized and bonded onto the side chain of polysulfone (PSF), giving two bidentate Schiff base ligand‐functionalized PSFs, PSF–SAN and PSF–SCA, referred to as macromolecular ligands. Following coordination reactions between the macromolecular ligands and Eu(III) and Tb(III) ions (the reaction occurred between the bonded ligands SAN or SCA and the lanthanide ion), two series of luminescent polymer–rare earth complexes, PSF–SAN–Eu(III) and PSF–SCA–Tb(III), were obtained. The two macromolecular ligands were fully characterized by Fourier transform infrared (FTIR), ¹H NMR and UV absorption spectroscopy, and the prepared complexes were also characterized by FTIR, UV absorption spectroscopy and thermo‐gravity analysis. On this basis, the photoluminescence properties of these complexes and the relationships between their structure and luminescence were investigated in depth. The results show that the bonded bidentate Schiff base ligands, SAN and SCA, can effectively sensitize the fluorescence emission of Eu(III) and Tb(III) ions, respectively. PSF–SAN–Eu(III) series complexes, namely the binary complex PSF–(SAN)₃–Eu(III) and the ternary complex PSF–(SAN)₃–Eu(III)–(Phen)₁ (Phen is the small‐molecule ligand 1,10‐phenanthroline), produce strong red luminescence, suggesting that the triplet state energy level of SAN is lower and well matched with the resonant energy level of the Eu(III) ion. By contrast, PSF–SAN–Eu(III) series complexes, namely the binary complex PSF–(SCA)₃–Tb(III) and the ternary complex PSF–(SCA)₃–Tb(III)–(Phen)₁, display strong green luminescence, suggesting that the triplet state energy level of SCA is higher and is well matched with the resonant energy level of Tb(III).     

Synthesis,characterization and cytotoxic/cytostatic activity of La(III) and Dy(III) complexes

New La(III) and Dy(III) complexes of deprotonated 4-hydroxy-3[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (Acenocoumarol) were synthesized and characterized using FT-IR, FT-Raman, ¹H NMR spectra, and elemental analyses. The ligand and its lanthanide(III) complexes were tested for their cytotoxic/cytostatic activity against two tumor cell lines and peritoneal mouse macrophages. The La(III) and Dy(III) complexes exhibit good activity against melanoma B16 and fibrosarcoma L929 and they are stronger inhibitors of tumor cell proliferation compared to the ligand without influencing normal cell viability and NO release by mouse peritoneal macrophages.     

A spectroscopic study of the reaction of NAMI, a novel ruthenium(III)anti-neoplastic complex, with bovine serum albumin.

The reaction of Na[transRuCl4Me2SO(Im)] (NAMI; where Im is imidazole), a novel anti-neoplastic ruthenium(III) complex, with BSA, was studied in detail by various physico-chemical techniques. It is shown that NAMI, following chloride hydrolysis, binds bovine serum albumin tightly; spectrophotometric and atomic absorption data point out that up to five ruthenium ions are bound per albumin molecule when BSA is incubated for 24 h with an eightfold excess of NAMI. CD and electronic absorption results show that the various ruthenium centers bound to albumin exhibit well distinct spectroscopic features. The first ruthenium equivalent produces a characteristic positive CD band at 415 nm whereas the following NAMI equivalents produce less specific and less marked spectral effects. At high NAMI/BSA molar ratios a broad negative CD band develops at 590 nm. Evidence is provided that the bound ruthenium centers remain in the oxidation state +3. By analogy with the case of transferrins it is proposed that the BSA-bound ruthenium ions are ligated to surface histidines of the protein; results from chemical modification experiments with diethylpyrocarbonate seem to favor this view. Spectral patterns similar to those shown by NAMI are observed when BSA is reacted with two strictly related ruthenium(III) complexes Na[transRuCl4(Me2SO)2] and H(Im)[transRuCl4(Im)2] (ICR), implying a similar mechanism of interaction in all cases. It is suggested that the described NAMI-BSA adducts may form in vivo and may be relevant for the biological properties of this complex; alternatively NAMI/BSA adducts may be tested as specific carriers of the ruthenium complex to cancer cells. Implications of these findings for the mechanism of action of NAMI and of related ruthenium(III) complexes are discussed.     

The effect of lanthanum on electrophoretic mobility and passive cation movements of the Ehrlich ascites tumor cell.

We have investigated the effects of La+3 binding to the surface of Ehrlich ascites tumor cells on cell electrophoretic mobility and passive movements of Na+ and K+. Incubation of tumor cells in La+3-containing media results in a La+3 concentration-dependent decrease in net surface charge negativity. At [La+3] greater than 0.5 mM, the net surface charge becomes positive with maximum positivity occurring at [La+3] = 0.9 mM. The effects of La+3 binding on passive Na+ and K+ movements were investigated by following 22Na and K+ losses from ouabain-inhibited cells. Neither low (0.02) nor high (1.0 mM) [La+3] had any effect on the K+ efflux rate coefficient. 22Na losses from control and La+3-treated cells were consistent with washouts from two cellular compartments. Low [La+3] (0.02 mM) was without effect on Na+ losses from the cells. However, higher [La+3] (1.0 mM) resulted in a 48% inhibition of Na+ loss from the more slowly exchanging compartment. These results are not consistent with simple electrostatic interactions exerting a major influence on the passive movements of Na+ and K+. It is suggested that La+3 interacts with sites specific for Na+, perhaps involved in a carrier-mediated exchange system.     

Dependence of the inhibitory effect of metal cations on rat liver mitochondrial Ca2+ uptake on their physico-chemical properties

It has been found that Sr2+, La3+ Mn2+ (10-50 microM) inhibit Ca2+ transport into mitochondria in a competitive manner. Cd2+ ions show the mixed type inhibition of this transport. The inhibitory constants (Ki, microM) of the metals cations effect on Ca2+ transport increases in such a sequence: La3+ (2,11), Cd2+ (10,36), Mn2+ (49,29), Sr2+ (66,43). The metals cations inhibitory effect has an insignificant dependence on their ionic radii. But it is good correlated with the series of metals cations, based on the stability constants of their complexes with acetate (r = -0.96), aspartic (r = -0.91) and glutaminic acids and their hydratation enthalpy (r = -0.78). These data reveal that hydratation of metals cations and their interaction with carboxyles of Ca(2+)-uniporter plays an important role in the process of Ca2+ transport into mitochondrial matrix space and its inhibition by the metals cations. The mixed type inhibition of mitochondrial Ca2+ uptake by Cd2+ seems to be caused by the partial de-energization of mitochondria owing to Cd2+ interaction with SH-containing respiratory chain components and pore-forming ligands of mitochondrial membrane.     

Interaction of chromium(III) complex of chiral binaphthyl tetradentate ligand with DNA

Since conformation of the molecule plays a vital role in the activity of drug, we have investigated the DNA interaction of a chromium(III) complex with ligands in two conformations. Chromium(III) complexes derived from chiral binaphthyl Schiff base ligands, viz. R- and S-2,2'-bis(salicylideneamino) 1,1'-binaphthyl, have been synthesized and characterized by mass, IR, and electronic spectra. The interaction of these R- and S-binaphthyl Schiff base chromium(III) complexes with CT-DNA was investigated with the goal of examining whether the chirality has an influence on the chromium(III)-DNA binding properties. The difference in chirality of the ligand did not show any striking difference in binding properties. The binding constants for R and S conformers were estimated to be 18 (+/-0.4) x 10(3) and 9.4 (+/-0.3) x 10(3) M(-1), respectively, through spectroscopic titrations. All the experimental results are suggestive that both the isomers are DNA groove binders. The results of steady-state as well as time-resolved fluorescence experiments, however, suggest that the R conformer has restricted mobility when bound to DNA because it is more deeply buried in the groove of DNA compared to the S isomer.     

Circularly polarized luminescence studies of the ternary complexes formed by Tb(III) with (S,S)-ethylenediamine-N,N′-disuccinic acid and achiral substrate ligands

Circularly polarized luminescence spectroscopy has been used to study the ternary complexes formed by Tb(III) with (S,S)-ethylenediamine-N,N′-disuccinic acid (EDDS) and a series of achiral carboxylate ligands. The 1:1 Tb(EDDS) complexes form polynuclear species at low pH values, and only oxalic acid was able to interfere with this process. At elevated pH values the Tb(EDDS) compounds become monomeric, and are capable of forming ternary complexes. When the steric requirements of the substrate ligand were small, no perturbation of the EDDS stereochemistry was noted. However, certain strongly binding bidentate ligands with larger steric requirements were found to interact with the coordinated EDDS ligand. Evidence was also obtained which indicated that strongly binding terdentate ligands could partially displace one or more of the ligating carboxylates of the EDDS ligand.     

The relationship between metal-metal distance of two metal ions chelated complex and RNA cleavage activity.

We prepared a series of ligands possessing two binding sites for metal coordination: in each ligand molecule, two binding sites with the same functionality (2,2'-dipicolylamino group) were placed at the of various methyl arenes. Thus, the distances between the metal binding sites were different from ligand to ligand. We examined the rate of the hydrolysis of RNA dimer catalyzed by La3+ ion binuclear complexes of the ligands. The catalytic activity of the binuclear complexes increased as the distance between the metal binding sites was decreased.     

Resonance Raman and lifetime studies on regioselectively deuteriated ruthenium(II) polypyridyl complexes.

Two series of ruthenium(II) polypyridyl complexes [Ru(bipy)(2)(phpytr)](+) and [Ru(bipy)(2)(phpztr)](+) (where Hphpytr = 2-(5-phenyl-1H-[1,2,4]triazol-3-yl)-pyridine and Hphpztr = 2-(5-phenyl-1H-[1,2,4]triazol-3-yl)-pyrazine) are examined by electrochemistry, UV/Vis, emission, resonance Raman, transient resonance Raman and transient absorption spectroscopy, in order to obtain a more comprehensive understanding of their excited state electronic properties. The interpretation of the results obtained is facilitated by the availability of several isotopologues of each of the complexes examined. For the pyridine-1,2,4-triazolato based complex the lowest emissive excited state is exclusively bipy based, however, for the pyrazine based complexes excited state localisation on particular ligands shows considerable solvent and pH dependency.     

Reaction of oxygen with 6-hydroxydopamine catalyzed by Cu, Fe, Mn, and V complexes: identification of a thermodynamic window for effective metal catalysis

In the autoxidation of 6-hydroxydopamine, we investigated the reactivity of metals and metal complexes with a range of abilities to catalyse the reaction with oxygen. Comparing the catalytic effectiveness of aquo metals at pH 7.4, copper accelerated autoxidation 61-fold, iron 24-fold, manganese 7.3-fold, and vanadium 5.7-fold. Copper was thus the most effective catalyst despite being the weakest oxidant, indicating reduction of oxygen as rate limiting. EDTA, which decreases the reduction potential of Fe(III)/Fe(II), increased catalysis by iron 74% to almost that of aquo copper. Conversely, EDTA inhibited catalysis by copper, manganese, and vanadium. Desferrioxamine strongly inhibited catalysis by all of the metals. Histidine prevented catalysis by copper, accelerated catalysis by iron (43%), and had little effect on catalysis by manganese or vanadium. ADP and phytate inhibited catalysis by iron and manganese (50% or more), accelerated catalysis by vanadium (10-27%), and had no effect on catalysis by copper. The effects of the ligands largely reflected their influence on the reduction potential of the metal. Accordingly, addition of NaBr, which increases the reduction potential of Cu(II)/Cu(I), inhibited by 50%. In contrast, Na2SO4 augmented catalysis by copper 3-fold. Consistent with effects of OH- on reduction potentials and on metal coordination to 6-hydroxydopamine, an increase in pH to 8.0 decreased catalysis by copper and iron, but increased that of manganese 10-fold. In conclusion, the catalytic effectiveness of the metal-ligand complexes are largely attributable to their reduction potential, with steric accessibility playing secondary roles. The results delineate a window of catalytically effective potentials suitable for facile reduction and reoxidation by oxygen. By extension the results identify factors determining the pro- and antioxidant roles of ligands in metal mediated reduction of oxygen.     

Spectral and thermodynamic properties of Ag(I), Au(III), Cd(II), Co(II), Fe(III), Hg(II), Mn(II), Ni(II), Pb(II), U(IV), and Zn(II) binding by methanobactin from Methylosinus trichosporium OB3b

Methanobactin (mb) is a novel chromopeptide that appears to function as the extracellular component of a copper acquisition system in methanotrophic bacteria. To examine this potential physiological role, and to distinguish it from iron binding siderophores, the spectral (UV–visible absorption, circular dichroism, fluorescence, and X-ray photoelectron) and thermodynamic properties of metal binding by mb were examined. In the absence of Cu(II) or Cu(I), mb will bind Ag(I), Au(III), Co(II), Cd(II), Fe(III), Hg(II), Mn(II), Ni(II), Pb(II), U(VI), or Zn(II), but not Ba(II), Ca(II), La(II), Mg(II), and Sr(II). The results suggest metals such as Ag(I), Au(III), Hg(II), Pb(II) and possibly U(VI) are bound by a mechanism similar to Cu, whereas the coordination of Co(II), Cd(II), Fe(III), Mn(II), Ni(II) and Zn(II) by mb differs from Cu(II). Consistent with its role as a copper-binding compound or chalkophore, the binding constants of all the metals examined were less than those observed with Cu(II) and copper displaced other metals except Ag(I) and Au(III) bound to mb. However, the binding of different metals by mb suggests that methanotrophic activity also may play a role in either the solubilization or immobilization of many metals in situ.     

Role of the Ca-pectates on the accumulation of heavy metals in the root apoplasm

In order to better understand the processes that regulate the accumulation in the apoplasm of heavy metals and their mobilization by the plant metabolites it is essential to study the mechanisms that regulate the interactions between metal ions and pectins. In such a context, the sorption of Cd(II), Zn(II), Cu(II) and Pb(II) from single and multi-metal solutions, by a Ca-polygalacturonate gel with a degree of esterification of 18.0 (PGAM₁) and 65.5% (PGAM₂) was studied in the 3.0–6.0 pH range in the presence of CaCl₂ 2.5 mM. The sorption of Cr(III) from single metal solution was also considered. The results show that the amount of each metal ion sorbed increases with increasing the initial metal ion concentration and pH. The data from the single metal solution tests show that at pH 6.0 the affinity of the metal ions towards the PGAM₁ matrix follows the order: Cr(III) > Cu(II) ? Pb(II) ? Zn(II) ? Cd(II). The simultaneous sorption of the bivalent metal ions by the PGAM₁ gels indicates that Pb(II) is selectively sorbed. The FT-IR spectra show that the carboxylate groups are mainly responsible for the metal ion coordination. The ability of PGAM₂ to accumulate Cr(III), Cu(II), and Pb(II) was lower than that found in the PGAM₁ systems whereas the sorption of Zn(II) and Cd(II) was negligible.