Factors governing the metal coordination number in isolated group IA and IIA metal hydrates

Many of the group IA and IIA metal ions, such as Na+, K+, Mg2+, and Ca2+, play crucial roles in biological functions. Previous theoretical studies generally focus on the number of water molecules bound to a particular (as opposed to all) alkali or alkaline earth cations and could not establish a single preferred CN for the heavier alkali and alkaline earth ion-water complexes. Crystal structures of hydrated Na+, K+, and Rb+ also cannot establish the preferred number of inner-shell water molecules bound to these cations. Consequently, it is unclear if the gas-phase CNs of group IA metal hydrates increase with increasing ion size, as observed for the group IIA series from the Cambridge Structural Database, and if the same factors govern the gas-phase CNs of both group IA and IIA ion-water complexes. Thus, in this work, we determine the number of water molecules directly bound to the series of alkali (Li+, Na+, K+, and Rb+) and alkaline earth (Be2+, Mg2+, Ca2+, Sr2+, and Ba2+) metal ions in the gas phase by computing the free energy for forming an isolated metal-aqua complex as a function of the number of water molecules at 298 K. The preferred gas-phase CNs of group IA hydrates appear insensitive to the ion size; they are all 4, except for Rb+, where a CN of 6 seems as likely. In contrast, the preferred gas-phase CNs of the group IIA dications increase with increasing ion size; they are 4 for Be2+, 6 for Mg2+ and Ca2+, and 7 for Sr2+ and Ba2+. An entropic penalty disfavors a gas-phase CN greater than 4 for group IA hydrates, but it does not dictate the gas-phase CNs of group IIA hydrates. Instead, interactions between the metal ion and first-shell water molecules and between first-shell and second-shell water molecules govern the preferred gas-phase CNs of the group IIA metal hydrates.     

Empirical force fields for biologically active divalent metal cations in water

We have presented a strategy for deriving ion-water van der Waals (vdW) parameters that implicitly include the microscopic solvent molecular effects around the ion. The strategy can be used to obtain vdW parameters for metal cations of the same formal charge and known experimental hydration free energies. In this work, it was applied to derive the vdW parameters for 24 divalent metal ions with measured hydration free energies ranging from -300 to -572 kcal/mol, coordination numbers (CNs) from 4 to 15, and ion-O (water) distances from 1.67 to 2.90 angstroms. The strategy used to derive the vdW parameters employs (1) a numerical procedure that links the coupling parameter used in free energy simulations with the experimental hydration free energies and (2) the first-shell CNs and structure for the entire series of divalent cations. One of the parameter sets obtained (referred to as MWc) simultaneously reproduces the observed (i) relative hydration free energies, (ii) first-shell CNs, and (iii) average ion-water distances of all the dications studied. In particular, the MWc parameters reproduce the observed (i) decrease in the CN from 6 for Cu2+ to 4 for Be2+, (ii) no change in the CN of 6 for dications with hydration free energies between those of Cu2+ and Cd2+, and (iii) an expansion of the CN from 6 for Cd2+ to 9.5 for Ba2+. The ion-water parameters derived herein represent a first step in the simulations of metalloproteins, which will also require potential energy functions incorporating polarizability, charge transfer, and other electronic effects to accurately model the protein-metal interactions in aqueous solution.     

Manganese(II)-containing MRI contrast agent employing a neutral and non-macrocyclic ligand

The ligand N,N'-bis(2-pyridylmethyl)-bis(ethylacetate)-1,2-ethanediamine (debpn) coordinates divalent transition metal ions in either a pentadentate or hexadentate fashion. The coordination number correlates with the ionic radius of the metal ion, with larger cations being heptacoordinate as assessed by solid-state analysis. With Mn(II), the debpn ligand is hexadentate and remains bound to the oxophilic metal ion, even when dissolved in water. The ligand's incomplete coordination of the manganous ion allows water molecules to coordinate to the metal center. These two properties, coupled with the high paramagnetism associated with the S = 5/2 metal center, enable [Mn(debpn)(H(2)O)](ClO(4))(2) to serve as a stable and effective magnetic resonance imaging contrast agent despite the ligand's lack of both a macrocyclic component and an anionic charge.     

Factors governing the protonation state of cysteines in proteins: an Ab initio/CDM study

The detailed mechanism of metal-cysteine binding is still poorly understood. It is not clear if every metal cation can induce cysteine deprotonation, how the dielectric medium affects this process, and the extent to which other ligands from the metal's first and second coordination shell influence cysteine ionization. It is also not clear if the zinc cation, with its positive charge reduced by charge transfer from the first two bound cysteinates, could still assist deprotonation of the next one or two cysteines in Cys3His and Cys4 zinc-finger cores. Here, we elucidate the factors governing the cysteine protonation state in metal-binding sites, in particular in Zn.Cys4 complexes, using a combined ab initio and continuum dielectric approach. Transition metal dications such as Zn2+ and Cu2+ and trivalent cations such as Al3+ with pronounced ability to accept charge from negatively charged Cys- are predicted to induce cysteine deprotonation, but not "hard" divalent cations such as Mg2+. A high dielectric medium was found to favor cysteine deprotonation, while a low one favored the protonated state. Polarizable ligands in the metal's first shell that can competitively donate charge to the metal cation were found to lower the efficiency of the metal-assisted cysteine deprotonation. The calculations predict that the zinc cation could assist deprotonation of all the cysteines during the folding of Cys4 zinc-finger cores and the [Zn.(Cys-)4]2- state is likely to be preserved in the final folded conformation of the protein provided the binding site is tightly encapsulated by backbone peptide groups or lysine/arginine side chains, which stabilize the ionized cysteine core.     

Ab initio study of intriguing coordination complexes: a metal field theory picture

Two noninnocent ligands are theoretically studied using wave function based methods to demonstrate their ability to undergo singlet-triplet transition under the effect of an external charge mimicking the electrostatic role of a metal ion. It is shown that the singlet-triplet energy difference is very sensitive to the metal ion charge which tunes the HOMO-LUMO energy difference of these ligands. While the latter is reduced as the charge is enhanced in the glyoxal-bis-(2-mercaptoanil) (gma) ligand, it is increased in the bis(imino)pyridine diradical ligand. This result shows a strong analogy with the crystal field theory, interchanging the roles played by the metal ion and the ligand. As the metal ion is explicitly treated in the Fe(gma)CN complex, this analogy can be pushed further resulting in a "metal field theory" conceptualization.     

DFT study of electronic structure of saccharin,thiosaccharin, and their respective ions: Effects of metal coordination on thiosaccharinate electronic structure

A rationalization of the conspicuous different abilities of saccharin and thiosaccharin to form coordination compounds with the first series of transition metal elements and to interact with heavy metal cations is sought. Their electronic molecular structures as well as those of their respective ions are compared performing natural bond orbitals (NBO) analyses of the four species. Upon deprotonation, the negative charge at the N atom in saccharin is almost constant while it decreases in thiosaccharin and the negative charge at the monocoordinated chalcogen atom is notably more increased in the latter than in the former. Apparently, the negative charge reorganization makes difficult the coordination of thiosaccharin with the first series of transition metal elements and favors its experimentally observed interaction with heavy metal cations such as cadmium, lead, mercury, silver, and thallium. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

Coordination Numbers of Central Atoms in Coordination Compounds

A sample of structurally characterized 10000 complexes (X-ray diffraction data) was carefully selected from available databases for analysis of coordination numbers (CNs) of their central atoms (complexing agents). The coordination numbers of various chemical elements are tabulated for their different oxidation numbers (ONs). Variations in CN with the ordinal number of an element in the Periodic Table were followed. A general distribution of the sample complexes over the CNs of the central atom, as well as their distributions for particular ONs, is displayed. References to particular coordination compounds are given for extreme and very uncommon CNs of a central atom with different ONs. A general pattern of the observed variations in the CN of chemical elements can be useful for predicting the properties of complexes, constructing their stability models, designing compounds with rich and unique properties, and developing retrieval and graphic tools for chemical databases.     

First principles study and database analyses of structural preferences for sodium ion (Na+) solvation and coordination

Extensive computations were performed on aqueous clusters of monovalent sodium cation [Na⁺(H₂O) _n ; (n = 1–20)] using MP2/cc-pVTZ and density functional theory. The structure, energy, and coordination number (CN) preference of a large number of competing conformations of different complexes have been explored. For complexes up to n = 12, the CN 4 is most preferred while 5, 6 CNs are favored in case of larger complexes containing up to 20 water molecules. These results are in very good agreement with experimental observations. The strength of hydrogen bonding among the waters coordinated to the Na⁺ ion is found to play a major role in the stability of the complexes. The varying preferences for CN of Na⁺ ion were explored by screening two important databases: Protein Databank and Cambridge Structural Database. A linear correlation is observed between the M (Metal)–O distance and the charge on metal ion in complex with the increase in CN of metal ion.     

A calix(4)arene pyridine derivative and its monomeric component: structural and thermodynamic aspects of their complexation with metal cations

The interaction of a calix(4)arene derivative, namely 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra[2-(4-pyridyl)methoxy]calix(4)arene, 1a, and its monomeric component, p-tert-butylphenoxy-4-pyridine, 1b, with metal cations has been investigated in acetonitrile and methanol. (1)H NMR measurements carried out in CD(3)CN show the primary role played by the pyridyl nitrogens in their complexation with metal cations. Conductance measurements demonstrated that for all cations (except mercury) the composition of the metal ion complexes of 1a is 1:1 (ligand:metal cation). However, 1a hosts two mercury cations per unit of ligand. For the monomer 1b, complexes of 2:1 (ligand:metal cation) stoichiometries are formed with the exception of Pb(2+) (1:1 composition). The thermodynamics of complexation of these systems are reported in acetonitrile. Data in methanol are limited to stability constant values for mercury(II) and these ligands. This paper demonstrates for the first time that thermodynamic data for the complexation of the monomeric component of the ligand and metal cations contribute significantly to the interpretation of systems involving cation-calixarene interactions in solution.     

Gas-phase reactions of divalent Ni complex ions with acetonitrile: Chelate ring size,inductive, and steric effects

Ni(II) complexes of a series of pentadentate polyamine ligands have been reacted with CH₃CN in the gas phase using a modified quadrupole ion trap mass spectrometer. The ligands have structural features such that upon complexation, chelate ring size, sterics, and inductive effects can be evaluated in the gas phase. Rate and equilibrium constants for CH₃CN addition to the metal complexes show that there is a general decrease in the gas-phase reactivity as the chelate ring size is increased. Density functional theory calculations at the B3LYP/LANL2DZ level of theory have been used to obtain minimum energy structures and Mulliken charges for the complexes. The decreased reactivity observed as the chelate ring size is increased correlates with a decrease in the atomic charge on the metal. A larger chelate ring size enhances ligand flexibility and improves the overlap of the ligand’s donor atoms with the metal center. Adding methyl groups adjacent to or on the nitrogen donor groups of a ligand also decreases the rate and equilibrium constants for the reactions of a given complex with CH₃CN. Analysis of Mulliken charges for these complexes indicates that both inductive and steric effects are responsible for lower complex reactivity. These results suggest that while the gas-phase reactivity of a metal complex with CH₃CN is very dependent on the functional groups directly bound to the metal, in some cases steric effects can conceal the correlation between reactivity and coordination structure.     

Transition metal complexes of the pentacyanocyclopentadienide anion

The ready formation of a range of transition metal complexes of the pentacyanocyclopentadienide anion via ligand transfer reactions employing Na[C(5)(CN)(5)] indicates that the [C(5)(CN)(5)](-) anion has an extensive transition metal coordination chemistry and is not such a weakly coordinating anion.     

Multicolor fluorescence of a styrylquinoline dye tuned by metal cations

A styrylquinoline dye with a dipicolylamine (DPA) moiety (1) has been synthesized. The dye 1 in acetonitrile demonstrates multicolor fluorescence upon addition of different metal cations. Compound 1 shows a green fluorescence without cations. Coordination of 1 with Cd(2+) shows a blue emission, while with Hg(2+) and Pb(2+) exhibits yellow and orange emissions, respectively. The different fluorescence spectra are due to the change in intramolecular charge transfer (ICT) properties of 1 upon coordination with different cations. The DPA and quinoline moieties of 1 behave as the electron donor and acceptor units, respectively, and both units act as the coordination site for metal cations. Cd(2+) coordinates with the DPA unit. This reduces the donor ability of the unit and decreases the energy level of HOMO. This results in an increase in HOMO-LUMO gap and blue shifts the emission. Hg(2+) or Pb(2+) coordinate with both DPA and quinoline units. The coordination with the quinoline unit decreases the energy level of LUMO. This results in a decrease in HOMO-LUMO gap and red shifts the emission. Addition of two different metal cations successfully creates intermediate colors; in particular, the addition of Cd(2+) and Pb(2+) at once creates a bright white fluorescence.     

Complexation of common metal cations by cyanins: Binding affinity and molecular structure

The ability of diverse metal cations to form complexes with cyanin has been investigated by means of Density Functional Theory (DFT) and the Quantum Theory of Atoms in Molecules (QTAIM). The strongest preference is shown by trivalent metals which exceed that of Mg(II), indicating that ion replacement processes are suitable detoxification mechanisms for plants. Molecular structure analysis indicates that the larger the metal affinity of Cy⁻ the longer the C2-C1’ bond length and smaller ρ_b value. This is understood as upon metal complexation the Cy⁻ ligand molecular structure is more compatible with a dienolate-like structure rather than the 4′-keto-quinoidal-like structure. The weight of the former increases as stronger the binding. QTAIM charges indicate that the stronger the binding energy the larger the charge transfer from Cy⁻ to the metal, reducing its positive charge below the values indicated by the corresponding Lewis structure.     

A DFT/CDM Study of metal-carboxylate interactions in metalloproteins: factors governing the maximum number of metal-bound carboxylates

The number of negatively charged metal-bound Asp/Glu residues determines the net charge of the carboxylate-rich metal-binding site, which has been found to play a role in enhancing the affinity and/or selectivity of a protein cavity for a given metal cofactor. Therefore, it is of interest to know the maximum number of carboxylates that could bind to a given metal (M(q)()(+)) of charge q and the key factors determining this upper limit in protein cavities, which are usually relatively buried. Using density functional theory combined with the continuum dielectric method to compute the H(2)O --> CH(3)COO(-) exchange free energies, the maximum number of carboxylates bound to M(q)()(+) in a relatively buried metal-binding site is found to depend on (i) the metal charge, q, (ii) the carboxylate-binding mode, and (iii) the first-shell carboxylate-second-shell ligand interactions. The maximum number of carboxylates bound to M(q)()(+) in a fully/partially solvent inaccessible protein cavity would not likely exceed q + 2 if (a) the metal-bound Asp/Glu side chains are hydrogen bonded to a Lys/Arg side chain or several peptide backbone amides/Asn/Gln side chains in the metal's second coordination shell or (b) at least one acidic residue binds bidentately, as opposed to monodentately, to the metal cofactor. This number is reduced to q + 1 in the absence of stabilizing interactions from outer-shell ligand(s) and if all the carboxylates are bound monodentately to the metal cofactor in a buried cavity. The computational results are consistent with findings from a PDB survey of uni-, di-, and trivalent metal-binding sites containing Asp/Glu residues.     

Impact of ligand protonation on eigen-type metal complexation kinetics in aqueous systems

The impact of ligand protonation on metal speciation dynamics is quantitatively described. Starting from the usual situation for metal complex formation reactions in aqueous systems, i.e., exchange of water for the ligand in the inner coordination sphere as the rate-determining step (Eigen mechanism), expressions are derived for the lability of metal complexes with protonated and unprotonated ligand species being involved in formation of the precursor outer-sphere complex. A differentiated approach is developed whereby the contributions from all outer-sphere complexes are included in the rate of complex formation, to an extent weighted by their respective stabilities. The stability of the ion pair type outer-sphere complex is given particular attention, especially for the case of multidentate ligands containing several charged sites. It turns out that in such cases, the effective ligand charge can be considerably different from the formal charge. The lability of Cd(II) complexes with 1,2-diaminoethane-N,N'-diethanoic acid at a microelectrode is reasonably well predicted by the new approach.     

Novel mixed ligand coordination compounds of some rare earth metal cations containing acesulfamato/N,N-diethylnicotinamide

The mixed ligand coordination compounds containing acesulfamato and N,N -diethylnicotinamide biomolecules of some rare earth metal cations (Eu³⁺, Tb³⁺, Ho³⁺, Er³⁺ and Yb³⁺) were synthesized, and their structural properties were investigated. Possible structural formulas have been proposed by determining the chemical composition of molecules (elemental analysis), binding properties (infrared spectroscopy, mass analysis, solid-state UV-vis spectroscopy), thermal degradation properties (TGA / DTA curves). Based on the data collected, it is suggested that rare earth metal cations with a 3+ oxidation state have sextet coordination. The geometries of the structures were thought to be distorted octahedral. The charge balance of the coordination sphere is balanced by a monoanionic acesulfamato located outside the coordination sphere. When the thermal behaviours of the complexes were examined, it was determined that the compounds with Eu³⁺, Tb³⁺, and Yb³⁺ metal cations contained one hydrate water outside the coordination sphere. Hydrate waters do not exist in the Ho³⁺ and Er³⁺ metal cation-centred complexes. At the end of the thermal decomposition analysis of all complex structures, it was determined that they leave the relevant metal oxides in the reaction vessels as final decomposition products.     

Non-covalent interactions of alkali metal cations with singly charged tryptic peptides

The complexes formed by alkali metal cations (Cat(+) = Li(+), Na(+), K(+), Rb(+)) and singly charged tryptic peptides were investigated by combining results from the low-energy collision-induced dissociation (CID) and ion mobility experiments with molecular dynamics and density functional theory calculations. The structure and reactivity of [M + H + Cat](2+) tryptic peptides is greatly influenced by charge repulsion as well as the ability of the peptide to solvate charge points. Charge separation between fragment ions occurs upon dissociation, i.e. b ions tend to be alkali metal cationised while y ions are protonated, suggesting the location of the cation towards the peptide N-terminus. The low-energy dissociation channels were found to be strongly dependant on the cation size. Complexes containing smaller cations (Li(+) or Na(+)) dissociate predominantly by sequence-specific cleavages, whereas the main process for complexes containing larger cations (Rb(+)) is cation expulsion and formation of [M + H](+). The obtained structural data might suggest a relationship between the peptide primary structure and the nature of the cation coordination shell. Peptides with a significant number of side chain carbonyl oxygens provide good charge solvation without the need for involving peptide bond carbonyl groups and thus forming a tight globular structure. However, due to the lack of the conformational flexibility which would allow effective solvation of both charges (the cation and the proton) peptides with seven or less amino acids are unable to form sufficiently abundant [M + H + Cat](2+) ion. Finally, the fact that [M + H + Cat](2+) peptides dissociate similarly as [M + H](+) (via sequence-specific cleavages, however, with the additional formation of alkali metal cationised b ions) offers a way for generating the low-energy CID spectra of 'singly charged' tryptic peptides.     

Coordination numbers of hydrated divalent transition metal ions investigated with IRPD spectroscopy

Hydration of the divalent transition metal ions, Mn, Fe, Co, Ni, Cu, and Zn, with 5-8 water molecules attached was investigated using infrared photodissociation spectroscopy and photodissociation kinetics. At 215 K, spectral intensities in both the bonded-OH and free-OH stretch regions indicate that the average coordination number (CN) of Mn(2+), Fe(2+), Co(2+), and Ni(2+) is ~6, and these CN values are greater than those of Cu(2+) and Zn(2+). Ni has the highest CN, with no evidence for any population of structures with a water molecule in a second solvation shell for the hexa-hydrate at temperatures up to 331 K. Mn(2+), Fe(2+), and Co(2+) have similar CN at low temperature, but spectra of Mn(2+)(H(2)O)(6) indicate a second population of structures with a water molecule in a second solvent shell, i.e., a CN < 6, that increases in abundance at higher temperature (305 K). The propensity for these ions to undergo charge separation reactions at small cluster size roughly correlates with the ordering of the hydrolysis constants of these ions in aqueous solution and is consistent with the ordering of average CN values established from the infrared spectra of these ions.     

Complexation ion chromatography —an overview of developments and trends in trace metal analysis

Complexation ion chromatography (IC), including all ion chromatographic modes in which complexation is exploited for the separation and detection of metal ions in different ways, is now a widely accepted method of trace metal analysis. Some of the significant advances in the theoretical aspects and practical applications of complexation IC modifications (non-suppressed cation chromatography with complex- forming mobile phases, coordination chromatography with chelate-forming bonded phases, ion-exchange and ion-pair chromatography of anionic metal chelates) recently developed in the authors' laboratories are reviewed. The retention behaviour and separation mechanism of non-complexed and completed metal analytes are discussed from the point of view of basic coordination chemistry (stability of metal complexes, effective charge of metal atom, ligand completing ability, etc.). Comparisons and contrasts between various metal complexation IC techniques and their common features and advantages relative to other methods used in analyses for transition and heavy metal ions are evaluated.     

First-second shell interactions in metal binding sites in proteins: a PDB survey and DFT/CDM calculations

The role of the second shell in the process of metal binding and selectivity in metalloproteins has been elucidated by combining Protein Data Bank (PDB) surveys of Mg, Mn, Ca, and Zn binding sites with density functional theory/continuum dielectric methods (DFT/CDM). Peptide backbone groups were found to be the most common second-shell ligand in Mg, Mn, Ca, and Zn binding sites, followed (in decreasing order) by Asp/Glu, Lys/Arg, Asn/Gln, and Ser/Thr side chains. Aromatic oxygen- or nitrogen-containing side chains (Tyr, His, and Trp) and sulfur-containing side chains (Cys and Met) are seldom found in the second coordination layer. The backbone and Asn/Gln side chain are ubiquitous in the metal second coordination layer as their carbonyl oxygen and amide hydrogen can act as a hydrogen-bond acceptor and donor, respectively, and can therefore partner practically every first-shell ligand. The second most common outer-shell ligand, Asp/Glu, predominantly hydrogen bonds to a metal-bound water or Zn-bound histidine and polarizes the H-O or H-N bond. In certain cases, a second-shell Asp/Glu could affect the protonation state of the metal ligand. It could also energetically stabilize a positively charged metal complex more than a neutral ligand such as the backbone and Asn/Gln side chain. As for the first shell, the second shell is predicted to contribute to the metal selectivity of the binding site by discriminating between metal cations of different ionic radii and coordination geometries. The first-shell-second-shell interaction energies decay rapidly with increasing solvent exposure of the metal binding site. They are less favorable but are of the same order of magnitude as compared to the respective metal-first-shell interaction energies. Altogether, the results indicate that the structure and properties of the second shell are dictated by those of the first layer. The outer shell is apparently designed to stabilize/protect the inner-shell and complement/enhance its properties.