Vanadium(V) complexes derived from triphenylphosphonium and hydrazides: cytotoxicity evaluation and interaction with biomolecules.

The development of coordination compounds with antineoplastic therapeutic properties is currently focused on non-covalent interactions with deoxyribonucleic acid (DNA). Additionally, the interaction profiles of these compounds with globular plasma proteins, particularly serum albumin, warrant thorough evaluation. In this study, we report on the interactions between biomolecules and complexes featuring hydrazone-type imine ligands coordinated with vanadium. The potential to enhance the therapeutic efficiency of these compounds through mitochondrial targeting is explored. This targeting is facilitated by the derivatization of ligands with triphenylphosphonium groups. Thus, this work presents the synthesis, characterization, interactions, and cytotoxicity of dioxidovanadium(V) complexes (C1-C5) with a triphenylphosphonium moiety. These VV-species are coordinated to hydrazone-type iminic ligands derived from (3-formyl-4-hydroxybenzyl)triphenylphosphonium chloride ([AH]Cl) and aromatic hydrazides ([H2L1]Cl-[H2L5]Cl). The structures of the five complexes were elucidated through single-crystal X-ray diffraction and vibrational spectroscopies, confirming the presence of dioxidovanadium(V) species in various geometries with degrees of distortion (τ = 0.03-0.50) and highlighting their zwitterionic characteristics. The molecular structural stability of C1-C5 in solution was ascertained using 1H, 19F, 31P, and 51V-nuclear magnetic resonance. Moreover, their interactions with biomolecules were evaluated using diverse spectroscopic methodologies and molecular docking, indicating moderate interactions (Kb ≈ 104 M-1) with calf thymus DNA in the minor groove and with human serum albumin, predominantly in the superficial IB subdomain. Lastly, the cytotoxic potentials of these complexes were assessed in keratinocytes of the HaCaT lineage, revealing that C1-C5 induce a reduction in metabolic activity and cell viability through apoptotic pathways.

Synthesis, characterization, solution chemistry and anticancer activity of [NiCl2(Ph2P-N(R)-PPh2)] (R = 2-CH2Py, CH2Ph and p-tol) complexes.

In this work three Ni2+ complexes with general formula [NiCl2(Ph2P-N(R)-PPh2)], R = 2-CH2Py (Py = pyridine) - 1, CH2Ph (Ph = phenyl) - 2 and p-tol (p-tol = p-tolyl) - 3, were synthesized and characterized. These complexes were obtained in high yield by the reaction of NiCl2.6H2O and the corresponding diphenylphosphinoamine ligand (Ph2P-N(R)-PPh2) in CH2Cl2/MeOH (1:1) solution, at room temperature (∼25 °C), and characterized by 1H and 31P {1H} NMR, vibrational spectroscopy in the infrared region, electronic spectroscopy in the UV-Vis regions, elemental analysis (%C, %H, %N) and single-crystal X-ray diffraction. The solution chemistry was studied in CDCl3/dmso-d6 (dimethylsulfoxide) or neat dmso-d6 using complex 2 as a model. The complexes were evaluated as cytotoxic agents against two cancer cells lines, A549 (lung cancer cells), B16F10 (melanoma cells) and the health cells HaCaT (human epithelial keratinocytes).

A Vanadium(V) complexes derived from pyridoxal/salicylaldehyde. Interaction with CT-DNA/HSA, and molecular docking assessments.

With the increasing development of metallopharmaceuticals, coordination compounds become viable alternatives for therapeutic uses. Despite the importance of platinum derivatives in this area, first-row transition metals complexes are welcome due to their characteristics. Vanadium is a promising metal in this context, as it has a range of compounds with different biological applications, including anticancer therapeutic effects. In this effort, the study of interactions between coordination compounds with deoxyribonucleic acid and with human serum albumin is fundamental. In this way, ten iminic ligands were synthesized by condensing p-substituted aromatic benzohydrazides (OH, CH3, H, NO2, and NH2) with salicylaldehyde (L1As-L5As) or pyridoxal hydrochloride (L1P-L5P). These ligands have characteristics that allow the tridentate coordination of vanadium cations, leading to the formation of ten vanadium(V) complexes (C1As-C5As and C1P-C5P) with different structural features, all characterized by single-crystal X-ray diffraction, UV-Vis and infrared spectroscopies, and cyclic voltammetry. In addition, the complexes were tested for their interactions with calf thymus deoxyribonucleic acid and human serum albumin by spectroscopic assays and molecular docking calculations. These new results can contribute to further research and provide different ways to design new vanadium complexes with biological applications.

Pyridoxal water-soluble cobalt(II) helicates: Synthesis, structural analysis, and interactions with biomacromolecules.

Helical complexes composed of organic ligand strands and metallic centers, called helicates, present interactions with biomacromolecules, such as deoxyribonucleic acid, as one of their main biological applications in bioinorganic chemistry. Despite the potential antineoplastic and antibacterial results of the interactions between helicates and biomacromolecules, there is still a gap of research in the literature, primarily in terms of solubility in aqueous media. In this study, we present the synthesis, structural analysis, and interaction with biomacromolecules of two water-soluble cobalt(II) double-stranded helicates: [CoII2L22][CoII(NCS)4]∙9H2O (C1) and [CoII2L42]Cl2∙11H2O (C2). These complexes are obtained from iminic ligands (L2 and L4) derived from pyridoxal, a vitamin B6 aldehyde derivative. Through spectroscopic assays, these helical complexes were shown to have weak and moderate binding capacities with calf-thymus deoxyribonucleic acid and human serum albumin, respectively. The theoretical assays suggest that C1 and C2 interact with the minor groove of deoxyribonucleic acid and have different main binding sites with human serum albumin. Furthermore, Van der Waals and hydrogen bonds were shown to be the main intermolecular forces for these C1-C2:biomacromolecules interactions.

Antiproliferative activity and energy calculations of a new triterpene isolated from the palm tree Acrocomia totai.

Acrocomia totai Mart (Arecaceae) is a palm tree native to South America, widely studied for biodiesel production. The aim of this work was to perform the first phytochemical study of A. totai leaves, as well as to do biological assays against human cancer cell lines. A new triterpene of the hopane class named totaiol (1), three known triterpenes (2-4), and two phytosteroids (5-6) were identified. The new natural product was characterized using 1 D and 2 D NMR, single crystal X-ray diffraction analises, and high resolution mass spectrometry. The intercontacts in the crystal packing were also analised. Complete stereochemical characterization of compound 1 revealed an unusual positioning pattern for methyl and isopropenyl groups in the polycyclic skeleton. Compounds 1-5 were evaluated for the first time in antiproliferative assays against Ca Ski, MCF-7 and MCF-10 cells. The new natural product was active against Ca Ski cells with IC50 ≤ 6.25 µg mL-1.

Diorganyl Diselenides and Iron(III) Chloride Drive the Regio- and Stereoselectivity in the Selenation of Ynamides.

We report here our results on the application of ynamides as substrates in the reactions with diorganyl dichalcogenides and iron(III) chloride to give selectively three different types of compounds: E-α-chloro-ß-(organoselenyl)enamides, 4-(organochalcogenyl)oxazolones, and vinyl tosylates. The results reveal that the selectivity in the formation of products was obtained by controlling the functional groups directly bonded to the nitrogen atom of the ynamides. Thus, α-chloro-ß-(organoselenyl) enamide derivatives were exclusively obtained when the TsN- and MsN-ynamides were treated with a mixture of diorganyl diselenides (1.0 equiv) and FeCl3 (3.0 equiv) in dichloroethane (DCE, 3 mL), at room temperature. The 4-(organochalcogenyl)oxazolones were selectively obtained with ynamides having an ester group, directly bonded to the nitrogen atom, upon treatment with a solution of FeCl3 (1.5 equiv) and diorganyl dichalcogenides (1.0 equiv) in dichloromethane (3 mL) at room temperature. Finally, vinyl tosylates were obtained from ynamides having an ester group, directly bonded to the nitrogen atom, by reaction with p-toluenesulfonic acid. We also studied the application of the prepared compounds as substrates for Suzuki and Sonogashira cross-coupling reactions.

Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer.

A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of ß-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a-g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013-8.78 µM, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK2.

Electrochemical, mechanistic, and DFT studies of amine derived diphosphines containing Ru(II)-cymene complexes with potent in vitro cytotoxic activity against HeLa and triple-negative breast cancer cells MDA-MB-231.

Complexes with general formula [RuCl(η6-p-cymene)(P-NR-P)]X (R = CH2Py (Py = pyridine) - [1a]+, CH2Ph (Ph = phenyl) - [1b]+, Ph - [1c] and p-tol (p-tol = p-tolyl) - [1d]+; X = PF6- or BF4-) were evaluated as cytotoxic agents against two cancer cell lines (HeLa and MDA-MB-231). All metal complexes are active in the range of concentrations tested (up to 100 µmol L-1). The IC50 (µmol L-1) values for the metal complexes are lower than that found for cisplatin. The activities are up to 6- and 15-fold higher than cisplatin for HeLa and MDA-MB-231 cancer cell lines, respectively. Studies of DNA binding and DNA cleavage were performed. DNA binding studies revealed a modest hypochromic shift in the metal complexes electronic spectra, indicating a weak interaction with Kb values in the range of 1.7 × 103-1.6 × 104. Although the cleavage tests revealed that in the dark DNA is not a biological target for these metal complexes, upon blue light irradiation they are activated causing DNA cleavage. Electrochemical studies showed the presence of two independent redox processes, one attributed to the oxidation process of Ru2+ → Ru3+ (EC process) and the other one to the reduction of Ru2+ → Ru1+, which is further reduced to Ru0 (ECE mechanism). In both processes, coupled chemical reactions were observed. DFT calculations were performed to support the electrochemical/chemical behavior of the complexes. The reactivity of complex [1b]BF4 with CH3CN was evaluated and two complexes were isolated [2b]BF4 and [3b]BF4. The complex mer-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4 ([2b]BF4) was isolated after refluxing the precursor [1b]BF4 in CH3CN. Isomerization of [2b]BF4 in CH3CN resulted in the formation of fac-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4. An attempt to isolate the fac-isomer by adding diethyl ether was unsuccessful, and the complex [3b]BF4 was observed as the major component. The complex [Ru2(µ-Cl3)(CH3CN)2(P-NCH2Ph-P)2]BF4 ([3b]BF4) proved to be very stable and can be obtained from both the mer- and the fac-isomers. The molecular structures of [1b]BF4 and [3b]BF4 were solved by single-crystal X-ray diffraction.

Synthesis of Selenochromenes via Dehydration of Arylalkynols Promoted by Iron(III) Chloride and Diorganyl Diselenides.

We report here the regioselective 6-endo-dig cyclization of [2-(butylselanyl)phenyl]propynols promoted by the cooperative action between diorganyl diselenides and iron(III) chloride leading to the formation of 4-methylene-3-(organoselanyl)-selenochromenes. The results of the reaction condition optimization studies showed that the solvent, the iron source, and the amount of diorganyl diselenide had a fundamental influence on the reaction yields. In the presence of iron(III) chloride (1.5 equiv) and diorganyl diselenides (1.0 equiv), using dichloromethane as the solvent, at room temperature, 4-methylene-3-(organoselanyl)-selenochromenes were formed in moderate to good yields. The reaction conditions were found to be suitable for substrates bearing electron-donating and electron-withdrawing groups on the aromatic ring at both propargyl and alkyne positions. However, we observed a limitation in the reaction conditions when they were applied to other diorganyl dichalcogenides, such as diorganyl disulfides and diorganyl ditellurides, which did not give the corresponding products. We also elaborated on a mechanism proposal based on control experiments performed.

Cyclization of Thiopropargyl Benzimidazoles by Combining Iron(III) Chloride and Diorganyl Diselenides.

A practical synthetic approach to the synthesis of 3-(organoselenyl)-imidazothiazines was developed. The methodology involved the regioselective 6-endo-dig cyclization of thiopropargyl benzimidazoles promoted by diorganyl diselenides and iron(III) chloride. The investigation to determine the best reaction conditions indicated the use of thiopropargyl benzimidazoles (0.25 mmol) with diorganyl diselenides (1.0 equiv) and iron(III) chloride (2.0 equiv) in dichloromethane at 40 °C for 30 min to be optimal. Under these conditions, the scope of the substrates was evaluated varying the structures of thiopropargyl benzimidazoles and diorganyl diselenides giving 28 3-(organoselenyl)-imidazothiazines in moderate to good yields. The reaction conditions were also applicable to diorganyl ditellurides; however, they did not work for diorganyl disulfides. The mechanism studies were carried out indicating that the cyclization proceeds via a cooperative action of diorganyl diselenides and iron(III) chloride, but a direct electrophilic cyclization, promoted by the in situ formed electrophilic organoselenium species, cannot be ruled out.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Sequential Carbon-Carbon/Carbon-Selenium Bond Formation Mediated by Iron(III) Chloride and Diorganyl Diselenides: Synthesis and Reactivity of 2-Organoselenyl-Naphthalenes.

In this paper, we report an intramolecular cyclization of benzylic-substituted propargyl alcohols promoted by iron(III) chloride and diorganyl diselenides to give 2-organoselenyl-naphthalenes via a sequential carbon-carbon/carbon-selenium bond formation. The present reaction tolerated a wide range of substituents in both propargyl alcohols and diorganyl diselenides to give the desired 2-organoselenyl-naphthalenes in good yields with high selectivity. In addition, O-acyl protected propargyl alcohol and propargyl bromide were also subjected to this protocol giving the corresponding 2-organoselenyl-naphthalenes. We found that dichalcogenide species affected the formation of cyclized products, whereas diorganyl diselenides gave high yields, moderate yields were obtained with diorganyl disulfides, and no product formation was found with diorganyl ditellurides. The key transformations could be attributed to the carbon-carbon triple bond activation of benzylic-substituted propargyl alcohols by a seleniranium ion, antiattack of the electron cloud from the aromatic ring at the activated triple bond, and cyclization via an exclusive 6-endo-dig process. We also found that the corresponding 2-organoselenyl-naphthalenes are suitable substrates to the selenium-lithium exchange reactions followed by trapping with aldehydes affording the corresponding secondary alcohols.

New insights into the SAR and drug combination synergy of 2-(quinolin-4-yloxy)acetamides against Mycobacterium tuberculosis.

2-(Quinolin-4-yloxy)acetamides have been described as potent and selective in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Herein, a new series of optimized compounds were found to demonstrate highly potent antitubercular activity, with minimum inhibitory concentration (MIC) values against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains in the submicromolar range. Furthermore, the most active compounds had no apparent toxicity to mammalian cells, and they showed intracellular activities similar to those of isoniazid and rifampin in a macrophage model of Mtb infection. Use of the checkerboard method to investigate the association profiles of lead compounds with first- and second-line antituberculosis drugs showed that 2-(quinolin-4-yloxy)acetamides have a synergistic effect with rifampin. Ultimately, the good permeability, moderate rates of metabolism and low risk of drug-drug interactions displayed by some of the synthesized compounds indicate that 2-(quinolin-4-yloxy)acetamides may yield candidates to use in the development of novel alternative therapeutics for tuberculosis treatment.

(Biphenyl-2-alkyne) derivatives as common precursors for the synthesis of 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes.

In this paper, we report our results on the cyclization of (biphenyl-2-alkyne) derivatives to give two different types of phenanthrene derivatives, 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes. The strategy for the synthesis was based on the use of electrophilic cyclization for the preparation of 9-iodo-10-organochalcogen-phenanthrenes and iron(iii) chloride/diorganyl diselenide-mediated intramolecular cyclization to prepare 9-organochalcogen-phenanthrenes. The effects of solvent, temperature, reaction time and stoichiometry on the efficiency of cyclization reactions were investigated. The standard reaction conditions were compatible with many functional groups in the substrates, such as methyl, chlorine, fluorine and methoxyl. This protocol was efficient for diorganyl diselenides and disulfides but ineffective for diorganyl ditellurides. The resulting phenanthrenes were further functionalized through Sonogashira reactions followed by the electrophilic cyclization reaction to give the selenophene-fused aromatic compounds.

Iron-Catalyzed Cyclization of Alkynols with Diorganyl Diselenides: Synthesis of 2,5-Dihydrofuran, 3,6-Dihydro-2H-pyran, and 2,5-Dihydro-1H-pyrrole Organoselanyl Derivatives.

An iron-catalyzed system, using diorganyl diselenides as an organoselenium source, was used for the cyclization of 1,4-butyne-diols in the preparation of 3,4-bis(organoselanyl)-2,5-dihydrofurans. The optimized reaction conditions are compatible with many functional groups in 1,4-butyne-diols and diorganyl diselenides. In addition, this catalyst system was also efficient with diorganyl disulfides, but it did not work for diorganyl ditellurides. The same reaction conditions were also extended to pentyne-1,5-diol for the preparation of 4,5-bis(organoselanyl)-3,6-dihydro-2H-pyrans and to 4-amino-butynol for the preparation of 2,5-dihydro-1H-pyrrole derivatives. The synthetic utility of these heterocycles was studied using 5-bis(organoselanyl)-3,6-dihydro-2H-pyrans as substrate in a Kumada-type cross-coupling reaction.

Iron(III) chloride and diorganyl diselenides-mediated 6-endo-dig cyclization of arylpropiolates and arylpropiolamides leading to 3-organoselenyl-2H-coumarins and 3-organoselenyl-quinolinones.

Combination of iron(III) chloride and diorganyl diselenides was used for cyclization of arylpropiolates and arylpropiolamides in formation of 3-organoselenyl-2H-coumarins and 3-organoselenyl-quinolinones, respectively. Systematic study to determine the ideal conditions revealed that the two substrates reacted in the same way using identical reaction conditions. The versatility of this method has been demonstrated by extension of the best reaction conditions to substrate having a variety of substituents. Analyses of the optimization reaction also showed that diorganyl diselenides have a dual role by acting as cycling agent and base to restore the aromatic system. Mechanistic investigation studies and analyses of the products obtained have revealed that the cyclization reactions follow an initial 6-endo-dig process to give the six-membered heterocycles without involving an intramolecular ipso-cyclization route.

Bis-vinyl selenides obtained via iron(III) catalyzed addition of PhSeSePh to alkynes: synthesis and antinociceptive activity.

In the present study the synthesis and antinociceptive activity of bis-vinyl selenides, prepared via FeCl(3) promoted reaction addition of diorganyl dichalcogenides to alkynes, is described. The pharmacological results demonstrated that bis-vinyl selenides 3a, 3d, 3h and 3t elicited antinociceptive effect in the mouse formalin test. The antinociceptive effects of bis-vinyl selenides are not sensitive to electronic effects of the substituents on the aromatic ring directly bonded to the selenium atom. Bis-vinyl selenides 3h and 3t were the most promising molecules for pharmacological purposes since these bis-vinyl selenides were effective in both phases of the formalin test and against edema. A single dose of bis-vinyl selenides 3a, 3d, 3h and 3t did not cause acute toxicity in mice.

Regioselective synthesis of isochromenones by iron(III)/PhSeSePh-mediated cyclization of 2-alkynylaryl esters.

A series of 4-Se-(Te, S)-isochromenones and 3-substituted isochromenones were synthesized in good yields via FeCl(3)-mediated cyclization of alkynylaryl esters with different diorganyl dichalcogenides. This methodology was carried out at room temperature, using inexpensive and environmentally friendly iron salts as metallic source and under air atmosphere. The reaction showed to be tolerant to a range of substituents bonded into the aromatic ring of the diorganyl dichalcogenides as well as to alkyl groups directly bonded to the chalcogen atom. Alternatively, the cyclization reaction of 2-alkynylaryl esters with FeCl(3), in the absence of diorganyl dichalcogenide, gave the isochromenones without the chalcogen moiety in the structure. This approach proved to be highly regioselective, providing only six-membered ring products, once the possible five-membered products were not observed in any experiments.

Synthesis of organochalcogen propargyl aryl ethers and their application in the electrophilic cyclization reaction: an efficient preparation of 3-halo-4-chalcogen-2H-benzopyrans.

We herein described the synthesis of various organochalcogen propargyl aryl ethers via reaction of lithium acetylide intermediate with electrophilic chalcogen (sulfur, selenium, tellurium) species. Various aryl and alkyl groups directly bonded to the chalcogen atom were used as electrophile. The results revealed that the reaction does not significantly depend on the electronic effects of substituents in the aromatic ring bonded to the chalcogen atom of the electrophilic chalcogen species. Additional versatility in this process was demonstrated with respect to a diverse array of functionality in the aromatic ring at propargyl aryl ethers. These propargyl aryl ethers, bearing the chalcogen group, underwent highly selective intramolecular cyclizations when treated with I(2) or ICl affording 3-iodo-4-chalcogen-2H-benzopyrans. The results demonstrated that the cyclization efficiency was significantly influenced by the steric effects of aromatic ring, since the cyclization reaction gave low yields with aromatic rings having a substituent at orto position than those having no substituent. The reactivity of 3-iodo-4-chalcogen-2H-benzopyrans was also studied. 4-Selenobutyl benzopyrans were treated under Neghishi cross-coupling conditions providing the corresponding 3-aryl benzopyran derivatives in good yields. In addition, using the copper catalyzed cross-coupling reactions with thiols, in the absence of any cocatalyst, we were able to introduce a thiol function in 3-iodo-benzopyran derivatives.

Chelation of ThIV, EuIII and NdIII by dianionic N,N'-bis(pyridoxylideneiminato)ethylene, (Pyr2en)2-. On the search of feasible modelings for heavy metals damage inhibition in living beings.

The neutral Schiff base N,N'-bis(pyridoxylideneiminato)ethylene {H(2)pyr(2)en} reacts with Th(NO(3))4.4H2O, NdCl3.6H2O and EuCl3.6H2O to give [Th(pyr(2)en)2(H2O)] (1), [Nd(pyr(2)en)(Hpyr(2)en)].12H2O (2) and [Eu(pyr(2)en)(Hpyr(2)en)] (3). In the three not yet reported bimolecular chelate systems the endo hydroxyl groups of the rings undergo deprotonation confirming the remarkable ability of the pyridoxal-containing ligand H(2)pyr(2)en to yield stable heavy metal chelates with unusual coordination polyhedra. Complexes 2 and 3 show a coordination number 8 for Nd and Eu, achieving a distorted quadratic antiprism. In complex 1 the additional water molecule increases the coordination number of Th to 9 producing a capped square antiprism. The synthesis and structural elucidation of the title complexes starting from a probably non-toxic metabolite like H(2)pyr(2)en should represent a useful contribution to the research on models of prevention and therapy of damage caused by radioactive and heavy elements.