Circularly Polarized Luminescence from New Heteroleptic Eu(III) and Tb(III) Complexes.

The complexes [Eu(bpcd)(tta)], [Eu(bpcd)(Coum)], and [Tb(bpcd)(Coum)] [tta = 2-thenoyltrifluoroacetyl-acetonate, Coum = 3-acetyl-4-hydroxy-coumarin, and bpcd = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N'-diacetate] have been synthesized and characterized from photophysical and thermodynamic points of view. The optical and chiroptical properties of these complexes, such as the total luminescence, decay curves of the Ln(III) luminescence, electronic circular dichroism, and circularly polarized luminescence, have been investigated. Interestingly, the number of coordinated solvent (methanol) molecules is sensitive to the nature of the metal ion. This number, estimated by spectroscopy, is >1 for Eu(III)-based complexes and <1 for Tb(III)-based complexes. A possible explanation for this behavior is provided via the study of the minimum energy structure obtained by density functional theory (DFT) calculations on the model complexes of the diamagnetic Y(III) and La(III) counterparts [Y(bpcd)(tta)], [Y(bpcd)(Coum)], and [La(bpcd)(Coum)]. By time-dependent DFT calculations, estimation of donor-acceptor (D-A) distances and of the energy position of the S1 and T1 ligand excited states involved in the antenna effect was possible. These data are useful for rationalizing the different sensitization efficiencies (ηsens) of the antennae toward Eu(III) and Tb(III). The tta ligand is an optimal antenna for sensitizing Eu(III) luminescence, while the Coum ligand sensitizes better Tb(III) luminescence {ϕovl = 55%; ηsens ≥ 55% for the [Tb(bpcd)(Coum)] complex}. Finally, for the [Eu(bpcd)(tta)] complex, a sizable value of glum (0.26) and a good quantum yield (26%) were measured.

Comparative study on removal of platinum cytostatic drugs at trace level by cysteine, diethylenetriamino functionalized Si-gels and polyethyleneimine functionalized sponge: Adsorption performance and mechanisms.

To efficiently remove trace Pt-based cytostatic drugs (Pt-CDs) from aqueous environments, a comparative investigation was conducted on the adsorption behavior of three commercial adsorbents including cysteine-functionalized silica gel (Si-Cys), 3-(diethylenetriamino) propyl-functionalized silica gel (Si-DETA) and open-celled cellulose MetalZorb® sponge (Sponge). The research on the adsorption of cisplatin and carboplatin encompasses investigations of pH dependence, adsorption kinetics, adsorption isotherms, and adsorption thermodynamics. The obtained results were compared with those of PtCl42- to better understand the adsorption mechanisms. The adsorption of cisplatin and carboplatin by Si-Cys was significantly better than Si-DETA and Sponge, which suggested that in chelation-dominated chemisorption, thiol groups provided high-affinity sites for Pt(II) complexation. Adsorption of the anion PtCl42- was more pH dependent and generally superior to that of cisplatin and carboplatin, benefiting from the contribution of ion association with protonated surfaces. The removal process of aqueous Pt(II) compounds occurred by the hydrolysis of complexes in solution and subsequent adsorption, and the specific adsorption process was explained by the synergistic action of ion association and chelation mechanisms. The rapid adsorption processes involving diffusion and chemisorption were well described by pseudo-second-order kinetic model. The isotherm studies suggested monolayer adsorption, consistent with the Langmuir model. Indicated from the adsorption enthalpy results, the chelation of cisplatin and carboplatin with thiol groups was an endothermic reaction, while the adsorption of PtCl42- was exothermic. At 343 K, Si-Cys achieved 98.5 ± 0.1 % (cisplatin) and 94.1 ± 0.1 % (carboplatin) removal. To validate the obtained findings, the described process was applied to urine samples doped with Pt-CDs as analog of hospital wastewaters and the removal was very efficient, ranging from 72 ± 1 % to 95 ± 1 %, when using Si-Cys as adsorbent, although limited matrix effects were observed.

Dynamics of the Energy Transfer Process in Eu(III) Complexes Containing Polydentate Ligands Based on Pyridine, Quinoline, and Isoquinoline as Chromophoric Antennae.

In this work, we investigated from a theoretical point of view the dynamics of the energy transfer process from the ligand to Eu(III) ion for 12 isomeric species originating from six different complexes differing by nature of the ligand and the total charge. The cationic complexes present the general formula [Eu(L)(H2O)2]+ (where L = bpcd2- = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate; bQcd2- = N,N'-bis(2-quinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate; and bisoQcd2- = N,N'-bis(2-isoquinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate), while the neutral complexes present the Eu(L)(H2O)2 formula (where L = PyC3A3- = N-picolyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetate; QC3A3- = N-quinolyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetate; and isoQC3A3- = N-isoquinolyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetate). Time-dependent density functional theory (TD-DFT) calculations provided the energy of the ligand excited donor states, distances between donor and acceptor orbitals involved in the energy transfer mechanism (RL), spin-orbit coupling matrix elements, and excited-state reorganization energies. The intramolecular energy transfer (IET) rates for both singlet-triplet intersystem crossing and ligand-to-metal (and vice versa) involving a multitude of ligand and Eu(III) levels and the theoretical overall quantum yields (ϕovl) were calculated (the latter for the first time without the introduction of experimental parameters). This was achieved using a blend of DFT, Judd-Ofelt theory, IET theory, and rate equation modeling. Thanks to this study, for each isomeric species, the most efficient IET process feeding the Eu(III) excited state, its related physical mechanism (exchange interaction), and the reasons for a better or worse overall energy transfer efficiency (ηsens) in the different complexes were determined. The spectroscopically measured ϕovl values are in good agreement with the ones obtained theoretically in this work.

Entropy and Enthalpy Effects on Metal Complex Formation in Non-Aqueous Solvents: The Case of Silver(I) and Monoamines.

Access to the enthalpy and entropy of the formation of metal complexes in solution is essential for understanding the factors determining their thermodynamic stability and speciation. As a case study, in this report we systematically examine the complexation of silver(I) in acetonitrile (AN) with the following monoamines: n-propylamine (n-pr), n-butylamine (n-but), hexylamine (hexyl), diethylamine (di-et), dipropylamine (di-pr), dibutylamine (di-but), triethylamine (tri-et) and tripropylamine (tri-pr). The study shows that the complex stabilities are quite independent of the length of the substitution chain on the N atom and demonstrates that, in general, the overall enthalpy terms associated with the complex formation are strongly exothermic, whereas the entropy values oppose the complex formations. In addition, we examined the similarity of the formation constants of AgL complexes of the primary monoamines in AN, dimethylsulfoxide (DMSO) and water, which were unexpected on the basis of the difference between the donor properties of solvents.

Regreening properties of the soil slow-mobile H2bpcd/Fe3+ complex: Steps forward to the development of a new environmentally friendly Fe fertilizer.

The application of synthetic Fe-chelates stands for the most established agronomical practice to alleviate lime-induced chlorosis, which still constitutes a major agronomic problem. However, the percolation through the soil profile due to the negative charge of the most deployed molecules results in agronomical and environmental problems. H2bpcd/Fe3+ complex features distinctive chemical characteristics, including moderate stability of the Fe(bpcd)+ species (logß ML = 20.86) and a total positive charge, and we studied its behavior in soil and regreening effects on cucumber plants. Soil column experiments have underlined that H2bpcd/Fe3+ is retained in more amounts than EDDHA/Fe3+. The new ligand was not proven to be toxic for the cucumber and maize seedlings. A concentration of 20 µM H2bpcd/Fe3+ attained regreening of Fe-deficient cucumber plants grown in the hydroponic solution supplied with CaCO3, similar to that shown by EDDHA/Fe3+. Experiments with a 2 µM concentration of 57Fe showed that cucumber roots absorbed H2bpcd/57Fe3+ at a slower rate than EDTA/57Fe3+. The high kinetic inertness of H2bpcd/Fe3+ may explain such behavior.

Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells.

The chiral cationic complex [Ru(η1 -OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2R ), isolated from reaction of [Ru(η1 -OAc)(η2 -OAc)(R,R)-Skewphos)(CO)] (1R ) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X=Y=OPiv 3R ; X=SAc, Y=OAc 4R ). The corresponding enantiomers 2S -4S have been obtained from 1S containing (S,S)-Skewphos. Reaction of 2R and 2S with (S)-cysteine and NaPF6 at pH=9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF6 (PP=(R,R)-Skewphos 2R -Cys; (S,S)-Skewphos 2S -Cys). The DFT energetic profile for 2R with (S)-cysteine in H2 O indicates that aquo and hydroxo species are involved in formation of 2R -Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n-octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT-116 and A549 cell lines with EC50 values of 2.8-0.04 µM. The (R,R)-Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4R (EC50 =0.04 µM) being 14 times more cytotoxic than 4S against the anaplastic thyroid cancer 8505 C cell line.

Thermodynamic Study of Oxidovanadium(IV) with Kojic Acid Derivatives: A Multi-Technique Approach.

The good chelating properties of hydroxypyrone (HPO) derivatives towards oxidovanadium(IV) cation, VIVO2+, constitute the precondition for the development of new insulin-mimetic and anticancer compounds. In the present work, we examined the VIVO2+ complex formation equilibria of two kojic acid (KA) derivatives, L4 and L9, structurally constituted by two kojic acid units linked in position 6 through methylene diamine and diethyl-ethylenediamine, respectively. These chemical systems have been characterized in solution by the combined use of various complementary techniques, as UV-vis spectrophotometry, potentiometry, NMR and EPR spectroscopy, ESI-MS spectrometry, and DFT calculations. The thermodynamic approach allowed proposing a chemical coordination model and the calculation of the complex formation constants. Both ligands L4 and L9 form 1:1 binuclear complexes at acidic and physiological pHs, with various protonation degrees in which two KA units coordinate each VIVO2+ ion. The joined use of different techniques allowed reaching a coherent vision of the complexation models of the two ligands toward oxidovanadium(IV) ion in aqueous solution. The high stability of the formed species and the binuclear structure may favor their biological action, and represent a good starting point toward the design of new pharmacologically active vanadium species.

Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action.

Phenanthriplatin (PtPPH) is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells. Although the aqua-activated drug has been assumed to be the precursor for DNA damage, it is still under debate whether the way in which that metallodrug attacks to DNA is dominated by a direct binding to a guanine base or rather by an intercalated intermediate product. Aiming to capture the mechanism of action of PtPPH, the present contribution used theoretical tools to systematically assess the sequence of all possible mechanisms on drug activation and reactivity, for example, hydrolysis, intercalation, and covalent damage to DNA. Ab initio quantum mechanical (QM) methods, hybrid QM/QM' schemes, and independent gradient model approaches are implemented in an unbiased protocol. The performed simulations show that the cascade of reactions is articulated in three well-defined stages: (i) an early and fast intercalation of the complex between the DNA bases, (ii) a subsequent hydrolysis reaction that leads to the aqua-activated form, and (iii) a final formation of the covalent bond between PtPPH and DNA at a guanine site. The permanent damage to DNA is consequently driven by that latter bond to DNA but with a simultaneous π-π intercalation of the phenanthridine into nucleobases. The impact of the DNA sequence and the lateral backbone was also discussed to provide a more complete picture of the forces that anchor the drug into the double helix.

Coordination of the Co2+ and Ni2+ Ions in Tf2N- Based Ionic Liquids: A Combined X-ray Absorption and Molecular Dynamics Study.

Molecular dynamics (MD) simulations and X-ray absorption spectroscopy (XAS) have been combined to study the coordination of the Co2+ and Ni2+ ions in ionic liquids (ILs) based on the bis(trifluoromethylsulfonyl)imide ([Tf2N]-) anion and having different organic cations, namely, 1-butyl-3-methylimidazolium ([C4mim]+), 1,8-bis(3-methylimidazolium-1-yl)octane ([C8(mim)2]2+), N,N,N-trimethyl-N-(2-hydroxyethyl)ammonium ([choline]+), and butyltrimethylammonium ([BTMA]+). Co and Ni K-edge XAS data have been collected on 0.1 mol L-1 Co(Tf2N)2 and Ni(Tf2N)2 solutions and on the metallic salts. MD simulations have been carried out to obtain structural information on the metal ion coordination. The analysis of the extended X-ray absorption fine structure (EXAFS) spectra of the solutions has been carried out based on the atomistic description provided by MD, and the studied ILs have been found to be able to dissolve both the Co(Tf2N)2 and Ni(Tf2N)2 salts giving rise to a different structural arrangement around the metal ions as compared to the solid state. The combined EXAFS and MD results showed that the Co2+ and Ni2+ ions are surrounded by a first solvation shell formed by six [Tf2N]- anions, each coordinating in a monodentate fashion by means of the oxygen atoms. The nature of the IL organic cation has little or no influence on the overall spatial arrangement of the [Tf2N]- anions, so that stable octahedral complexes of the type [M(Tf2N)6]4- (M = Co, Ni) have been observed in all the investigated ILs.

Isoquinoline-based Eu(iii) luminescent probes for citrate sensing in complex matrix.

A neutral Eu(iii) complex containing the S,S enantiomer of isoQC3A3- ligand (isoQC3A3- = N-isoquinolyl-N,N',N'-trans-l,2-cyclohexylenediaminetriacetate) was synthesized and characterized. The complex was spectroscopically investigated and the results compared with those obtained for the similar bis-anionic ligand bisoQcd2- (bisoQcd2- = N,N'-bis(2-isoquinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate). Both Eu(iii)-complexes show similar binding constants upon titration with the main analytes contained in interstitial extracellular fluid (i.e. hydrogen carbonate, serum albumin and citrate). However, the analyte affinity is accompanied by different enhancements of the Eu(iii) intrinsic quantum yield (QY). Structures and hydration numbers of the complexes are determined by luminescence decay measurements and DFT calculations. The QYs as well as the binding constants of the individual adducts of the complexes with hydrogen carbonate, bovine serum albumin (BSA) and citrate are determined. The study of the Eu(iii) emission upon the systematic variation of one analyte in a complex mixture has been carried out to predict the performance of the luminescent sensor in conditions close to the real extracellular environment. Both Eu(iii) complexes can detect citrate at extracellular concentrations up to 500 µM, even at millimolar concentrations of the other interfering species. In the case of the Eu(bisoQcd)OTf complex, an increase of 23% of the Eu(iii) luminescence intensity at 615 nm upon addition of 0.3 mM of citrate was recorded. This feature makes the latter complex a viable probe for luminescence analysis of citrate in a complex matrix.

Elusive Coordination of the Ag+ Ion in Aqueous Solution: Evidence for a Linear Structure.

X-ray absorption spectroscopy (XAS) has been employed to study the coordination of the Ag+ ion in aqueous solution. The conjunction of extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) data analysis provided results suggesting the preference for a first shell linear coordination with a mean Ag-O bond distance of 2.34(2) Å, different from the first generally accepted tetrahedral model with a longer mean Ag-O bond distance. Ab initio molecular dynamics simulations with the Car-Parrinello approach (CPMD) were also performed and were able to describe the coordination of the hydrated Ag+ ion in aqueous solution in very good agreement with the experimental data. The high sensitivity for the closest environment of the photoabsorber of the EXAFS and XANES techniques, together with the long-range information provided by CPMD and large-angle X-ray scattering (LAXS), allowed us to reconstruct the three-dimensional model of the coordination geometry around the Ag+ ion in aqueous solution. The obtained results from experiments and theoretical simulations provided a complex picture with a certain amount of water molecules with high configurational disorder at distances comprised between the first and second hydration spheres. This evidence may have caused the proliferation of the coordination numbers that have been proposed so far for Ag+ in water. Altogether these data show how the description of the hydration of the Ag+ ion in aqueous solution can be complex, differently from other metal species where hydration structures can be described by clusters with well-defined geometries. This diffuse hydration shell causes the Ag-O bond distance in the linear [Ag(H2O)2]+ ion to be ca. 0.2 Å longer than in isolated ions in solid state.

Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin.

The cationic enantiopure (R,R) and luminescent Eu(III) complex [Eu(bisoQcd)(H2O)2] OTf (with bisoQcd = N,N'-bis(2-isoquinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate and OTf = triflate) was synthesized and characterized. At physiological pH, the 1:1 [Eu(bisoQcd)(H2O)2]+ species, possessing two water molecules in the inner coordination sphere, is largely dominant. The interaction with bovine serum albumin (BSA) was studied by means of several experimental techniques, such as luminescence spectroscopy, isothermal titration calorimetry (ITC), molecular docking (MD), and molecular dynamics simulations (MDS). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digitoxin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the Eu(III) complexes. In fact, the presence of isoquinoline rings drives the corresponding complex toward the protein superficial area containing the tryptophan residue 134 (Trp134). As the main consequence, the metal center undergoes the loss of one water molecule upon interaction with the side chain of a glutamic acid residue. On the other hand, the similar complex containing pyridine rings ([Eu(bpcd)(H2O)2]Cl with bpcd = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate) interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules.

Effect of the Counterion on Circularly Polarized Luminescence of Europium(III) and Samarium(III) Complexes.

Each enantiopure europium(III) and samarium(III) nitrate and triflate complex of the ligand L, with L = N,N'-bis(2-pyridylmethylidene)-1,2-(R,R + S,S)-cyclohexanediamine ([LnL(tta)2]·NO3 and [LnL(tta)2(H2O)]·CF3SO3, where tta = 2-thenoyltrifluoroacetylacetonate) has been synthesized and characterized from a spectroscopic point of view, using a chiroptical technique such as electronic circular dichroism (ECD) and circularly polarized luminescence (CPL). In all cases, both ligands are capable of sensitizing the luminescence of both metal ions upon absorption of light around 280 and 350 nm. Despite small differences in the total luminescence (TL) and ECD spectra, the CPL activity of the complexes is strongly influenced by a concurrent effect of the solvent and counterion. This particularly applies to europium(III) complexes where the CPL spectra in acetonitrile can be described as a weighed linear combination of the CPL spectra in dichloromethane and methanol, which show nearly opposite signatures when their ligand stereochemistries are the same. This phenomenon could be related to the presence of equilibria interconverting solvated, anion-coordinated complexes and isomers differing by the relative orientation of the tta ligands. The difference between some bond lengths (M-N bonds, in particular) in the different species could be at the basis of such an unusual CPL activity.

Unusual Fluorescence Quenching-Based Al3+ Sensing by an Imidazolylpiperazine Derivative. ß-Cyclodextrin Encapsulation-Assisted Augmented Sensing.

We report in this paper an unusual ß-cyclodextrin mediated-aluminum (III) ion sensing based on augmented quenching of fluorescence. The fluorescent sensing of metal ions by a new ligand prepared (L = 4-[{4-(1H-imidazol-1-yl)phenyl]imino}methyl]piperazine-1-carboxaldehyde) has been investigated as well as the effect of the supramolecular complex formation with ß-CD. In aqueous solution, L shows an increase of fluorescence due to the interaction with ß-cyclodextrin with a formation constant of 77 (± 12) M-1. The ROESY NMR spectrum clearly indicates that L is encapsulated by ß-CD. Theoretical calculations show the possible structure both of the L-ß-CD adduct and of the coordination mode of Al3+ ion to L. In the presence of ß-CD, the piperazine adopts a distorted conformation. It leads to an enhanced Al3+ sensing by the compound in its supramolecular complexed form. The lower limit of detection of Al3+ ions is 6.00 × 10-8 mol L-1. This detection limit slightly expands for L in the presence of ß-CD.

Coordination of 2,2'-(Trifluoroazanediyl)bis(N,N'-dimethylacetamide) with U(VI), Nd(III), and Np(V): A Thermodynamic and Structural Study.

Thermodynamic properties of the complexation of 2,2'-(trifluoroazanediyl)bis(N,N'-dimethylacetamide) (CF3ABDMA) with U(VI), Nd(III), and Np(V) have been studied in 1.0 M NaNO3 at 25 °C. Equilibrium constants of the complexation were determined by potentiometry and spectrophotometry. In comparison with a series of structurally related amine-bridged diacetamide ligands, including 2,2'-(benzylazanediyl)bis(N,N'-dimethylacetamide) (BnABDMA), 2,2'-azanediylbis(N,N'-dimethylacetamide) (ABDMA), and 2,2'-(methylazanediyl)bis(N,N'-dimethylacetamide) (MABDMA), CF3ABDMA forms weaker complexes with U(VI), Nd(III), and Np(V) due to the lower basicity of the center N atom in CF3ABDMA resulting from the attachment of the strong electron-withdrawing CF3- moiety. The complexation strength of CF3ABDMA with the three metal ions follows the order: UO22+ > Nd3+ > NpO2+, consistent with the order of the "effective" charges of the metal ions. Structural information on the U(VI)/CF3ABDMA complexes in solution and in solid was obtained by theoretical computation, single crystal X-ray diffractometry, 19F NMR, and electrospray ionization mass spectrometry. The structural data indicate that, similar to the three previously studied amine-bridged diacetamide ligands (BnABDMA, ABDMA, and MABDMA), the CF3ABDMA ligand coordinates to UO22+ in a tridentate mode, through the center nitrogen and the two amide oxygen atoms.

Solvation of Zn2+ ion in 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids: a molecular dynamics and X-ray absorption study.

Molecular dynamics (MD) simulations and X-ray absorption spectroscopy (XAS) were employed to study the solvation of Zn2+ ion in dry [Cnmim][Tf2N] (n = 2, 4; 1-ethyl-3-methylimidazolium and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) room temperature ionic liquids (RTILs). For [C4mim][Tf2N] also a water-saturated system was considered. The thermodynamic parameters of single ion solvation and transfer from water to the RTIL, as well as the structural information, were calculated by means of MD simulations and our study evidences that both structural and thermodynamic features can be reproduced by MD in good agreement with the experimental data. In the case of [C4mim][Tf2N], enthalpies and entropies of solvation and transfer from water to the RTIL were also obtained. The Zn2+ ion results more favorably solvated in water than in the RTIL and this seems to be caused by the more negative entropy of solvation in the latter liquid. This can be explained by the higher ordering imposed by the metal ion when solvated in [C4mim][Tf2N] with respect to water. When the transfer of Zn2+ in a water/[C4mim][Tf2N] biphasic system is considered, the results show a positive value for the free energy of transfer and the metal ion always prefers to remain solvated in water than in the water-saturated RTIL phase. This theoretical result was confirmed by the analysis of XANES (X-ray absorption near edge structure) and the EXAFS (extended X-ray absorption fine structure) spectra of Zn(Tf2N)2 solutions in [C4mim][Tf2N] in the presence of water.

A new tripodal kojic acid derivative for iron sequestration: Synthesis, protonation, complex formation studies with Fe3+, Al3+, Cu2+ and Zn2+, and in vivo bioassays.

This work presents the simple and low cost synthesis of a new tripodal ligand, in which three units of kojic acid are coupled to a tris(2-aminoethyl)amine (tren) backbone molecule. The protonation equilibria, together with the complex formation equilibria of this ligand with Fe3+, Al3+, Cu2+ and Zn2+ ions were studied. The complementary use of potentiometric, spectrophotometric and NMR techniques, and of Density Functional Theory (DFT) calculations, has allowed a thorough characterization of the different species involved in equilibrium. The stability of the formed complexes with Fe3+ and Al3+ are high enough to consider the new ligand for further studies for its clinical applications as a chelating agent. Biodistribution studies were carried out to assess the capacity the ligand for mobilization of gallium in 67Ga-citrate injected mice. These studies demonstrated that this ligand efficiently chelates the radiometal in our animal model, which suggests that it can be a promising candidate as sequestering agent of iron and other hard trivalent metal ions. Furthermore, the good zinc complexation capacity appears as a stimulating result taking into a potential use of this new ligand in analytical chemistry as well as in agricultural and environmental applications.

Eu(iii) and Tb(iii) complexes of 6-fold coordinating ligands showing high affinity for the hydrogen carbonate ion: a spectroscopic and thermodynamic study.

In the present contribution, four classes of Ln(iii) complexes (Ln = Eu and Tb) have been synthesized and characterized in aqueous solution. They differ by charge, Ln(bpcd)+ [bpcd2- = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate] and Ln(bQcd)+ (bQcd2- = N,N'-bis(2-quinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate) being positively charged and Ln(PyC3A) (PyC3A3- = N-picolyl-N,N',N'-trans-l,2-cyclohexylenediaminetriacetate) and Ln(QC3A) (QC3A3- = N-quinolyl-N,N',N'-trans-l,2-cyclohexylenediaminetriacetate) being neutral. Combined DFT, spectrophotometric and potentiometric studies reveal the presence, under physiological conditions (pH 7.4), of a couple of equally and highly stable isomers differing by the stereochemistry of the ligands (trans-N,N and trans-O,O for bpcd2- and bQcd2-; trans-O,O and trans-N,O for PyC3A3- and QC3A3-). Their high log ß values (9.97 < log ß < 15.68), the presence of an efficient antenna effect and the strong increase of the Ln(iii) luminescence intensity as a function of the hydrogen carbonate concentration in physiological solution, render these complexes as very promising optical probes for a selective detection of HCO3-in cellulo or in extracellular fluid. This particularly applies to the cationic Eu(bpcd)+, Tb(bpcd)+ and Eu(bQcd)+ complexes, which are capable of guesting up to two hydrogen carbonate anions in the inner coordination sphere of the metal ion, so that they show an unprecedented affinity towards HCO3- (log K for the formation of the adduct in the 4.6-5.9 range).

Differential Metal Ion Sensing by an Antipyrine Derivative in Aqueous and ß-Cyclodextrin Media: Selectivity Tuning by ß-Cyclodextrin.

ß-Cyclodextrin (ß-CD) is a nontoxic cyclic oligosachcharide that can encapsulate all or part of organic molecules of appropriate size and specific shape through noncovalent interaction. Herein, we report the influence of ß-CD complex formation of an antipyrine derivative on its metal ion sensing behavior. In aqueous solution, the antipyrine shows a turn-on fluorescence sensing of vanadyl ion, and in cyclodextrin medium it senses aluminum ion. The compound shows an unusual fluorescence quenching on binding with ß-cyclodextrin (log KSV = 2.34 ± 0.02). The differential metal ion sensing is due to the partial blocking of the chelating moiety by the cyclodextrin molecule. The structure of the antipyrine-cyclodextrin complex is optimized by two-dimensional rotating-frame Overhauser effect spectroscopy. The binding constant is determined by isothermal titration calorimetry (log K = 2.09 ± 0.004). The metal ion binding site is optimized by quanutm mechanical calculations. The lower limit of detection of vanadyl and aluminum ions, respectively, are 5 × 10-8 and 5 × 10-7 mol dm-3. This is the first report of selectivity of two different cations by a chemosensor in water and in ß-CD.

Using Theory To Reinterpret the Kinetics of Monofunctional Platinum Anticancer Drugs: Stacking Matters.

The monofunctional platinum drug phenanthriplatin (phenPt) blocks the replication of cancer cells even if it reacts with only one guanine base. However, there is still insufficient experimental data to improve its cytotoxicity and all previously proposed chemical modifications of the parent structure have resulted in a loss of activity. We use theoretical tools to illustrate the key steps in the biological mechanisms of phenPt; that is, its activation in water and the subsequent attack on DNA. Our simulations suggest that the measured kinetic parameters, which are based on free nucleobases in solution, need to be reinterpreted because the self-assembled stacked reactive adduct formed in the reaction is inaccessible in real DNA. The constants reported here will help guide future work in the synthesis of anticancer platinum drugs.