Metal-ligand Binding Research Articles

Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes.

This paper describes the development of a simple empirical scoring function designed to estimate the free energy of binding for a protein-ligand complex when the 3D structure of the complex is known or can be approximated. The function uses simple contact terms to estimate lipophilic and metal-ligand binding contributions, a simple explicit form for hydrogen bonds and a term which penalises flexibility. The coefficients of each term are obtained using a regression based on 82 ligand-receptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validated error of 8.68 kJ/mol. Tests on internal consistency indicate that the coefficients obtained are stable to changes in the composition of the training set. The function is also tested on two test sets containing a further 20 and 10 complexes, respectively. The deficiencies of this type of function are discussed and it is compared to approaches by other workers.

Structure Enforced Assemblies of Porphyrin Based Metallomacrocycles. Control of Supramolecular Organization by Weak Interactions

Abstract Control of supramolecular organization by weak noncovalent interactions is demonstrated in a series of crystalline materials based on functionalized porphyrin building blocks. The monomeric units associate via metal-ligand binding, hydrogen-bonding and halogen-halogen interactions into pseudo-rigid polymeric arrangements with porous architecture, giving rise to the formation of a large variety of hetero-molecular inclusion-type materials.

A Model for Metal Affinity Protein Precipitation

We have modeled the kinetics of the metal affinity aggregation of proteins via a formalism that employs classical gelation theory in conjunction with ion binding equilibria. Simulations using our model indicate that the kinetics of coagulation are highly dependent on the pH of the solution, the pKaof the metal–ligand complex, and the molar ratio of metal ions to the metal binding sites on the protein surface. We have observed that very high metal ion concentrations and high metal–ligand binding constants serve to reduce the rate of aggregation. High proton concentrations also reduce the rate of aggregation by mass action competition with metal ions for proton binding sites. A novel post-gelation solution that incorporates a fragmentation term is used to account for the finite solubility at the end of the aggregation process. This fundamental model of the kinetics of metal affinity aggregation will help to relate aggregation process parameters to process performance.

Metal ligand binding to tyrosinase and the tyrosinase-related proteins

Laboratory of Cell Biology, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA

Density functional calculations of the structures and bond energies of Cr(CO)6 and (?6-C6H6) Cr(CO)2(CX) (X=O, S) complexes

Quantum chemical calculations based on density functional theory have been performed on Cr(CO)6, (η6-C6H6)Cr(CO)3 and (η6-C6H6)Cr(CO)2(CS) at the local and nonlocal level of theory using different functionals. Good agreement is obtained with experiment for both optimized geometries and metal-ligand binding energies. In particular, a comparison of metal-arene bond energies calculated for the (η6-C6H6)Cr(CO)3 and (η6-C6H6)Cr(CO)2(CS) complexes correlates well with kinetic data demonstrating that substitution of one CO group by CS leads to an important labilizing effect of this bond, which may be primarily attributed to a larger π-backbonding charge transfer to the CS ligand as compared with CO.

Automatic and accurate method for analysis of proteins that undergo hinge-mediated domain and loop movements

Background: The structures of proteins that undergo significant main-chain conformational change are reported with increasing frequency. Three-dimensional atomic models are often available for two alternative conformational states of the same molecule. Inspection has shown these states to be varied in nature, arising by mechanisms that include hinge-facilitated closure between domains and smaller-scale loop motions within domains; these movements are often induced by metal ion binding or ligand binding. Polypeptides that display flexible segments are also observed in different crystal conformations or as alternatively packed subunits. Although subjective visual inspection has been previously used to compare structures and analyze conformational changes, there is a need for an objective method.Results: We have developed a straightforward, robust, and objective algorithm that can locate the residues that mediate and participate in the changes between the two conformational states. Our method does not require initial superpositioning. We illustrate the method by considering several test cases. The first example is maltose binding protein, a polypeptide that exhibits rigid-body domain closure involving multiple hinges. The second is lactate dehydrogenase, which undergoes both loop and subdomain movement; we accurately describe the location and relative magnitude of these deformations. Finally, in the example of aspartate transcarbamoylase, both hinge-mediated domain movement and functionally relevant loop rearrangements are described. In the instances in which domain closure occurs, the residues that serve as hinges between the domains involved are accurately predicted. In addition, our technique successfully identifies the exact residues that undergo intra-domain loop movements, even for movements that are accompanied by larger scale inter-domain rearrangements.Conclusions: Our algorithm is successful in its comprehensive analysis and description of complex hinge-mediated domain motion for all structures displaying rigid-body movement and is accurate in identifying the location of any independent intra-domain rearrangements.

Trace elements in medicine: Speciation: the new frontier

Speciation of trace elements in body fluids and tissues of defining the many biocomponents to which the trace elements are bound and to explain their mobility, storage, retention and toxicity. Such new frontiers are now open for interdisciplinary research. It is necessary to maintain the integrity of the metal-ligand binding and to check the mass balance of the protein and the trace element throughout the isolation steps. A distinction is made between chemical speciation of the trace element and speciation as a part of cytology. Some methods are discussed for the speciation of As and Cr in serum, together with the limitations of the speciation procedure. It is assumed that the biomolecule and the trace element which are subsequently detected in the same fraction, are indeed associated with one another. This is not necessarily the case, so that confirmation with different means of identification of the biocomponent is imperative. A major problem in speciation work is due to the fact that immense hazards exist for contamination and losses of the trace element. In cytology, meaningful speciation cannot be achieved by ultracentrifugation of the different cell organelles. The best approach nowadays is to use microbeam techniques which are able to locate the trace element in situ, and even to attribute a semiquantitative value to its presence.

Stereochemical control over manganese(II)-thio versus manganese(II)-oxy coordination in adenosine 5'-O-(1-thiodiphosphate) complexes at the active site of creatine kinase

The stereochemical configurations of the Mn(II) complexes with the resolved epimers of adenosine 5'-O-(1-thiodiphosphate) (ADP alpha S), bound at the active site of creatine kinase, have been determined in order to assess the relative strengths of enzymic stereoselectivity versus Lewis acid/base preferences in metal-ligand binding. Electron paramagnetic resonance (EPR) data have been obtained for Mn(II) in anion-stabilized, dead-end (transition-state analogue) complexes, in ternary enzyme-MnIIADP alpha S complexes, and in the central complexes of the equilibrium mixture. The modes of coordination of Mn(II) at P alpha in the nitrate-stabilized, dead-end complexes with each epimer of ADP alpha S were ascertained by EPR measurements with (Rp)-[alpha-17O]ADP alpha S and (Sp)-[alpha-17O]ADP alpha S. The EPR spectrum for the complex with (Rp)-[alpha-17O]ADP alpha S showed inhomogeneous broadening due to unresolved superhyperfine coupling from coordinated 17O at P alpha. By contrast, the EPR spectrum for Mn(II) in complex with (Sp)-[alpha-17O]ADP alpha S is indistinguishable from that obtained for a matched sample with unlabeled (Sp)-ADP alpha S. A reduction in the magnitude of the 55Mn hyperfine coupling constant in the spectrum for the complex containing (Sp)-ADP alpha S is indicative of Mn(II)-thio coordination at P alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermodynamics of ion association: transition metal complexes of N-isobutyroyl- l-lysine

Calorimetric measurements have been made at 25°C in aqueous 0.1 M NaClO 4 for the formation of the mono- and bis- N-isobutyroyl- l-lysine complexes with copper(II), nickel(II), cobalt(II) and zinc(II). These data have been used in conjunction with previously determined stability constants, to calculate Δ G, Δ H and Δ S values for both protonation and metal complexation. These are discussed in terms of the nature of the metal ligand binding. All thermodynamic data are in agreement with the formation of glycine-like mono- and bis-chelates involving the α-amino and carboxyl groups.

Stereochemical consequences of the two-electron oxidation of a dirhodium fulvalene complex: the X-ray crystal structures of trans-[Rh2(CO)2(PPh3)2(η5:η′5-C10H8)] and cis-[Rh2(CO)2(PPh3)2(η5:η′5-C10H8)][PF6]2

Single-crystal X-ray diffraction studies on the dirhodium fulvalene complexes cis-[Rh2(CO)2(PPh3)2(η5:η′5-C10H8)][PF6]2(1) and trans-[Rh2(CO)2(PPh3)2(η5:η′5-C10H8)](2), both as their n-hexane solvates, show the structures to be dramatically different. In the dication of (1) the rhodium atoms lie on the same side of the fulvalene ligand and are bonded to one another with Rh–Rh 2.930(2)A; in (2) the metal atoms are on opposite sides of the hydrocarbon ligand at a separation of 5.662(1)A. A detailed comparison of the two structures shows that the oxidation of complex (2) to (1) also results in changes in the geometry of the metal–ligand binding: the Rh–P distances increase by 0.067(4)A; the ring centroid–Rh–P(CO) unit is planar in (2) but pyramidal in (1). The electronic factors behind the structural changes are examined by the extended-Huckel molecular-orbital method; the fulvalene ligands in complexes (1) and (2) have characteristics (C–C bond orders, ability to rotate about the central C–C bond) more similar to those of the fulvalene dianion than to free fulvalene. These conclusions are in accord with the structural observations, and with the assignment of formal oxidation states II and I to the rhodium atoms of (1) and (2) respectively. In the light of these results, brief comments are made on the apparently anomalous electrochemical behaviour of the complexes.

Copper-63 NMR studies of copper(I) complexes. Relationship between copper-63 chemical shift and metal-ligand binding

Copper-63 NMR studies of copper(I) complexes. Relationship between copper-63 chemical shift and metal-ligand binding

Solvent dependence of phthalocyanine redox equilibria

The phthalocyanines and porphyrins represent a unique series of complexes which can be varied almost inexhaustively via change of substituent, metal ion, axial ligand, spin state and coordination number, yet retain the basic MN4 unit. Detailed analysis of the variation of redox equilibria with each of these factors provides rare insights into the nature of metal ligand binding. Such data are therefore of fundamental value in the development of coordination chemistry, and in the elucidation of the redox (electron transfer, oxygen binding) roles played by metal ions in biological systems.

Intermolecular energy transfer between lanthanide complexes in aqueous solution—III: Studies of terbium(III) and europium(III) complexes of trimellitic, pyromellitic and trimesic acids

Intermolecular energy transfer, emission intensity, and emission lifetime measurements were used to study the solution phase coordination chemistry of terbium(III) and europium(III) complexes of trimellitic and pyromellitic acids at low pH. Solid polymeric compounds were found to precipitate out of solution once the pH reached 3.0, and these compounds were characterized by analytical means. In addition, the adduct formed between Tb 3+ and trimesic was also characterized and found to be polymeric. The trimellitic and pyromellitic acid complexes appear to begin metal-ligand binding as the pH is raised from 1.5 to 2.5, and polymeric association among the complexes appears to begin at a pH of 2.5. The extent of polymerization increases up to the point of precipitation.

ChemInform Abstract: AMBIDENT NUCLEOPHILES. VI. SOLUTION METAL‐LIGAND BINDING MODES IN PHOSPHORODITHIOATE COMPLEXES. A PHOSPHORUS‐31 NMR STUDY

Chemischer InformationsdienstVolume 9, Issue 7 Physical Organic Chemistry ChemInform Abstract: AMBIDENT NUCLEOPHILES. VI. SOLUTION METAL-LIGAND BINDING MODES IN PHOSPHORODITHIOATE COMPLEXES. A PHOSPHORUS-31 NMR STUDY C. GLIDEWELL, C. GLIDEWELLSearch for more papers by this author C. GLIDEWELL, C. GLIDEWELLSearch for more papers by this author First published: February 14, 1978 https://doi.org/10.1002/chin.197807064AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue7February 14, 1978 RelatedInformation

ChemInform Abstract: A STUDY OF METAL‐LIGAND VIBRATIONS IN NICKELOCENE AND FERROCENE

Raman and infrared spectra of nickelocene and ferrocene were studied as regards metal–ligand vibrations. It was found that the C5H5-ring tilt vibration, ν16(e1g), of nickelocene has considerably low frequency. This was discussed in view of metal–ligand binding between both metallocenes.

A Study of Metal–Ligand Vibrations in Nickelocene and Ferrocene

Abstract Raman and infrared spectra of nickelocene and ferrocene were studied as regards metal–ligand vibrations. It was found that the C5H5-ring tilt vibration, ν16(e1g), of nickelocene has considerably low frequency. This was discussed in view of metal–ligand binding between both metallocenes.

Thermodynamics of ion association XXV. Transition metal complexes of proline and hydroxyproline

Calorimetric and potentiometric measurements have been made at 25°C of the formation of the mono- and bis-hydroxyproline complexes of cobalt(II), nickel(II), copper(II) and zinc(II) and the proline complexes of copper(II) and nickel(II). The data have been used to calculate Δ G, Δ H and Δ S values for both protonation and metal complexation and these are discussed in terms of the nature of the metal—ligand binding.

Spectroscopic investigations of some neodymium complexes

The solution and reflection spectra of some neodymium complexes containing ligands having oxygen donors and nitrogen donors have been investigated. The red shifts of the visible and the near infrared bands have been correlated with the covalency parameter δ. The carboxylates and β-diketonates show weak covalent bonding. In the solid state, the nitrogen donor heterocyclic ligands and the oxide systems indicate strong metal-ligand covalent binding. In methanol solution however, the nitrogen heterocyclic ligands are weakly bonded to the neodymium ion. The solvent effect on the spectrum of trivalent neodymium is also discussed.

ESR and Optical Absorption Studies in Copper Diethyldithiocarbamate

ESR investigations at X band and optical-absorption measurements have been reported in single crystals of copper (II) diethyldithiocarbamate Cu[S2CN(C2H5)2]2 diluted to 0.2% with the corresponding zinc complex. The measurements have been made both at room and liquid-oxygen temperatures. ESR measurements gave the following values for the parameters in spin Hamiltonian g‖ = 2.1085, g⊥ = 2.023(6), A63 = 142.4×10−4 cm−1, A65 = 152.0×10−4 cm−1, B = 22.4×10−4 cm−1, Q′∼3×10−4 cm−1. Polarized optical absorption study has made possible a proper assignment of the absorption bands to their corresponding transitions. This has led to information regarding the ordering of the MO levels of the complex. The coefficients used in the MO description of the complex have been calculated from the observed parameters. The results show that the metal ligand B1g σ bond is purely covalent and that the out-of-plane π bonding is appreciably covalent whereas the in-plane π bonding is ionic. Further, it is noted that the metal ligand binding is more covalent with sulfur as ligand than with oxygen or nitrogen.