The solution structure of [Cu(aq)]2+ and its implications for rack-induced bonding in blue copper protein active sites

The structure of [Cu(aq)]2+ has been investigated by using full multiple-scattering theoretical (MXAN) analysis of the copper K-edge X-ray absorption (XAS) spectrum and density functional theory (DFT) to test both ideal Td and square-planar four-coordinate, five-coordinate square-pyramidal, and six-coordinate octahedral [Cu(aq)]2+ models. The best fit was an elongated five-coordinate square pyramid with four Cu-O(eq) bonds (2 x 1.98 +/- 0.03 A and 2 x 1.95 +/- 0.03 A) and a long Cu-O(ax) bond (2.35 +/- 0.05 A). The four equatorial ligands were D2d-distorted from the mean equatorial plane by +/-(17 +/- 4) degrees, so that the overall symmetry of [Cu(H2O)5]2+ is C2v. The four-coordinate MXAN fit was nearly as good, but the water ligands (4 x 1.96 +/- 0.02 A) migrated +/-(13 +/- 4) degrees from the mean equatorial plane, making the [Cu(H2O)4]2+ model again D2d-distorted. Spectroscopically calibrated DFT calculations were carried out on the C2v elongate square-pyramidal and D2d-distorted four-coordinate MXAN copper models, providing comparative electronic structures of the experimentally observed geometries. These calculations showed 0.85e spin on Cu(II) and 0.03e electron spin on each of the four equatorial water oxygens. All covalent bonding was restricted to the equatorial plane. In the square-pyramidal model, the electrostatic Cu-O(ax) bond was worth only 96.8 kJ mol(-1), compared to 304.6 kJ mol(-1) for each Cu-O(eq) bond. Both MXAN and DFT showed the potential well of the axial bond to be broad and flat, allowing large low-energy excursions. The irregular geometry and D2d-distorted equatorial ligand set sustained by unconstrained [Cu(H2O)5]2+ warrants caution in drawing conclusions regarding structural preferences from small molecule crystal structures and raises questions about the site-structural basis of the rack-induced bonding hypothesis of blue copper proteins. Further, previously neglected protein folding thermodynamic consequences of the rack-bonding hypothesis indicate an experimental disconfirmation.     

Dynamics of the interaction of vapor-deposited copper with alkanethiolate monolayers: bond insertion, complexation, and penetration pathways

We have investigated the interaction of vapor-deposited copper with -CH3, -OH, -OCH3, -COOH, and -CO2CH3 terminated alkanethiolate self-assembled monolayers (SAMs) adsorbed on polycrystalline Au using time-of-flight secondary ion mass spectrometry and density functional theory calculations. For -OH, -COOH, and -CO2CH3 terminated SAMs measurements indicate that for all copper coverages there is a competition between Cu atom bond insertion into C-O bonds, stabilization at the SAM/vacuum interface, and penetration to the Au/S interface. In contrast, on a -OCH3 terminated SAM Cu only weakly interacts with the methoxy group and penetrates to the Au substrate, while for a -CH3 terminated SAM deposited copper only penetrates to the Au/S interface. The insertion of copper into C-O terminal group bonds is an activated process. We estimate that the barriers for Cu insertion are 55 +/- 5 kJ mol(-1) for the ester, 50 +/- 5 kJ mol(-1) for the acid, and 55 +/- 5 kJ mol(-1) for the hydroxyl terminated SAMs. The activation barrier for the copper insertion is much higher for the -OCH3 SAM. Copper atoms with energies lower than the activation barrier partition between complexation (weak interaction) with the terminal groups and penetration through the monolayer to the Au/S interface. Weakly stabilized copper atoms at the SAM/vacuum interface slowly penetrate through the monolayer. In contrast to the case of Al deposition, C-O bond insertion is favored over C=O, C-H, and C-C bond insertion.     

Structure of a C26H28 alkene formed via titanium-promoted reductive dimerization of 4-(spirocyclopropyl)-pentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one

A spiro-fused C₂₆H₂₈ cage≓ dimer hydrocarbon contains two three-membered rings, two four-membered rings, eight five-membered rings, and two six-membered rings. The molecule is calculated by molecular mechanics to have 902 kJ/mol of strain energy distributed primarily between angle strain (457 kJ/mol) and torsional interactions (368 kJ/mol). Molecular mechanics calculations and a geometry-optimized ab initio calculation are used to analyze the bond lengths and bond angles in the molecule. There is one major discrepancy between observed and calculated distances.     

Correlation between DFT calculated and X-ray structures from CSD,for Cu(II) and Cu(I) coordination spheres when coordinated to four acyclic amine ligands. A reconsideration of copper(II) planarity

The Cambridge Crystallographic Database (CSD) shows [Cu^IIL₄]²⁺ complexes, L = acyclic amine, fitting well with theoretically calculated structures to describe a planar-to-flat tetrahedral transformation pathway. Statistically, the Cu^II “planar” coordination sphere shows two distinct sets of trans N–Cu–N bond angles, 180° and near 150°, with the latter somewhat energetically favored according to DFT results. The planar structure is not confirmed theoretically when an example of these molecules in the CSD is geometrically minimized, suggesting that crystallographic or packing forces help to generate the planar structure in the crystal. Results of energy calculations from DFT seem to explain this feature. Less planar and more tetrahedral examples in the CSD are also found and compare well with theoretically converged related molecules. Trans N–Cu–N bond angles near 130° seem feasible for both Cu^I and Cu^II coordination spheres. These copper complexes having the copper coordination sphere in a less tetrahedral geometry are suggested as potential alternative models for blue proteins, and they deserve further exploration.     

Bispidine copper(II) compounds: effects of the rigid ligand backbone

Approximative density-functional theory calculations indicate that the tetradentate ligand L (L = 2,4-bis-(2-pyridyl)-3,7-diaza-[3.3.1]-bicyclononane) enforces an unusual and strong binding of a co-ligand (substrate) to a copper(II) center. The co-ligand in [Cu(L)(Cl)](+) completes a square-pyramidal coordination around copper(II) and binds in the equatorial plane rather than on the apical position. This configuration is a stable geometric isomer for the model complex [Cu(NH3)2(imine)2(Cl)](+), but it is disfavored by approximately 10 kJ mol(-1) and not commonly observed for CuN4 chromophores with a monodentate co-ligand. The equatorial coordination increases the bond energy of the copper(II)-chloride bond by approximately 80 kJ mol(-1), and similar results are expected for other copper(II)-L-substrate complexes, some of which show strong catalytic activity or unusual stability. Despite the enforced configuration, L does not impose significant steric strain on the copper(II) center but is well preorganized for the Jahn-Teller labile ion in this unusual geometry. The preorganization extends to the orientation of the pyridine donors (torsion angle around the copper-pyridine bond), and this seems to be of importance in the reactivity of the copper-L complexes and their derivatives.     

Theoretical evidence for a NH...XC blue-shifting hydrogen bond: complexes pairing monohalomethanes with HNO

Correlated ab initio calculations are used to analyze the interaction between nitrosyl hydride (HNO) and CH3X (X = F, Cl, Br). Three minima are located on the potential energy surface of each complex. The more strongly bound contains a NH...X bond, along with CH...O; CH...O and CH...N bonds occur in the less stable minimum. Binding energies of the global minimum lie in the range of 11-13 kJ/mol, and there is little sensitivity to the identity of the halogen atom. Unlike most other such hydrogen bonds, the NH covalent bond in this set of complexes becomes shorter, and its stretching frequency shifts to the blue, upon forming the NH...X hydrogen bond. The amount of this blue shift varies in the order F > Cl > Br.     

Inner-sphere reorganization energy of iron-sulfur clusters studied with theoretical methods

Models of several types of iron-sulfur clusters (e.g., Fe(4)S(4)(SCH(3))(4)(2-/3-/4-)) have been studied with the density functional B3LYP method and medium-sized basis sets. In a vacuum, the inner-sphere reorganization energies are 40, 76, 40, 62, 43, and 42 kJ/mol for the rubredoxin, [2Fe-2S] ferredoxin, Rieske, [4Fe-4S] ferredoxin, high-potential iron protein, and desulfoferrodoxin models, respectively. The first two types of clusters were also studied in the protein, where the reorganization energy was approximately halved. This change is caused by the numerous NH.S(Cys) hydrogen bonds to the negatively charged iron-sulfur cluster, giving rise to a polar local environment. The reorganization energy of the iron-sulfur clusters is low because the iron ions retain the same geometry and coordination number in both oxidation states. Cysteine ligands give approximately the same reorganization energy as imidazole, but they have the advantage of stabilizing a lower coordination number and giving more covalent bonds and therefore more effective electron-transfer paths.     

Properties of Sulfur-Sulfur Bonds

SS bonds are extraordinarily flexible and have properties that are observed only on isolated occasions for other homonuclear bonds: the bond lengths very between 1.8 and 3.0Å, the bond angles between 90 and 180° and the dihedral angles between 0 and 180°; the bond energies amount to up to 430 kJ/mol. The SS stretching frequencies can appear over the range 177–820 cm^?1 and force constants of 1.4 to 6.3 mdyne/Å have been calculated. This variability is illustrated with examples containing isolated and cumulated SS bonds.     

Study of amino- and pyridyl-containing zinc(II) and cadmium(II) complexes by molecular mechanics using a force field based on the Gillespie-Kepert model

A new approach combining the molecular mechanics (MM) method and the Gillespie-Kepert model was applied to calculate the geometry and strain energy of zinc(II) and cadmium(II) complexes with amino- and pyridyl-containing ligands. High accuracy of calculations of the geometry was demonstrated for more than 20 complexes of these metals. Typical r.m.s. deviations between the calculated and experimental values (X-ray diffraction analysis) were 0.02 Å for bond lengths, 2° for bond angles, and 4° for torsion angles. The size-match selectivity of several macrocycles and polydentate open-chain ligands was studied. Correlations between the calculated strain energies of metal complexes and the experimental values of their stability constants and enthalpies of formation are discussed.     

The coordination of the catalytic zinc ion in alcohol dehydrogenase studied by combined quantum-chemical and molecular mechanics calculations

Summary The coordination number of the catalytic zinc ion in alcohol dehydrogenase has been studied by integrated ab initio quantum-chemical and molecular mechanics geometry optimisations involving the whole enzyme. A four-coordinate active-site zinc ion is 100–200 kJ/mol more stable than a five-coordinate one, depending on the ligands. The only stable binding site for a fifth ligand at the zinc ion is opposite to the normal substrate site, in a small cavity buried behind the zinc ion. The zinc coordination sphere has to be strongly distorted to accommodate a ligand in this site, and the ligand makes awkward contacts with surrounding atoms. Thus, the results do not support proposals attributing an important role to five-coordinate zinc complexes in the catalytic mechanism of alcohol dehydrogenase. The present approach makes it possible also to quantify the strain induced by the enzyme onto the zinc ion and its ligands; it amounts to 42–87 kJ/mol for four-coordinate active-site zinc ion complexes and 131–172 kJ/mol for five-coordinate ones. The four-coordinate structure with a water molecule bound to the zinc ion is about 20 kJ/mol less strained than the corresponding structure with a hydroxide ion, indicating that the enzyme does not speed up the reaction by forcing the zinc coordination sphere into a structure similar to the reaction intermediates.     

堆积效应与弱共价键分子结构的模拟

<正> 在有限的空间中排列物体时,被排列物体的几何因素对排列方式会产生影响。我们将这种效应称为“堆积效应”。用积木游戏可形象说明堆积效应。如在一个圆形积木盒中放进四块圆积木(图1),显然这些积木不能任意排列。积木B只能分别置于积木A的两侧。它们“摄动”的范围是很小的。同样,在配位化合物的分子结构中,配位空间只有4π立体角,     

Affinity-guided protein conjugation: the trilogy of covalent protein labeling,assembly and inhibition

Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an “affinity-guided covalent conjugation” strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative (which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made “reactive peptides” for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of “affinity-guided covalent conjugation” in various applications.     

Thermal degradation study of isotactic polypropylene using factor-jump thermogravimetry

The degradation of isotactic polypropylene in the range 390–465°C was studied using factor-jump thermogravimetry. The degradations were carried out in vacuum and at pressures of 5 and 800 mm Hg of N₂, flowing at 100–400 standard mL/s. At 800 mm Hg this corresponds to linear rates of 1–4 mm/s. In vacuum bubbling in the sample caused problems in measuring the rate of weight loss. The apparent activation energy was estimated as 61.5 ± 0.8 kcal/mol (257 ± 3 kJ/mol). In slowly flowing N₂ at 800 mm Hg pressure the activation energy was 55.1 ± 0.2 kcal/mol (230 ± 0.8 kJ/mol) for isotactic polypropylene and 51.1 ± 0.5 kcal/mol (214 ± 2 kJ/mol) for a naturally aged sample of atactic polypropylene. For isotactic polypropylene degrading at an external N₂ pressure of 5 mm Hg the apparent activation energy was 55.9 ± 0.3 kcal/mol (234 ± 1 kJ/mol). A simplified degradation mechanism was used with estimates of the activation energies of initiation and termination to give an estimate of 29.6 kcal/mol for the ß-scission of tertiary radicals on the polypropylene backbone. Initiation was considered to be backbone scission ß to allyl groups formed in the termination reaction. For initiation by random scission of the polymer backbone, as in the early stages of thermal degradation, an overall activation energy of 72 kcal/mol is proposed. The difference between vacuum and in-N₂ activation energies is ascribed to the latent heat contributions of molecules which do not evaporate as soon as they are formed. At these imposed rates of weight loss the average molecular weights of the volatiles in vacuum and in 8 and 800 mm H_g N₂ are in the ratios 1–1/2–1/9.     

Creation of a type 1 blue copper site within a de novo coiled-coil protein scaffold

Type 1 blue copper proteins uniquely coordinate Cu(2+) in a trigonal planar geometry, formed by three strong equatorial ligands, His, His, and Cys, in the protein. We designed a stable Cu(2+) coordination scaffold composed of a four-stranded α-helical coiled-coil structure. Two His residues and one Cys residue were situated to form the trigonal planar geometry and to coordinate the Cu(2+) in the hydrophobic core of the scaffold. The protein bound Cu(2+), displayed a blue color, and exhibited UV-vis spectra with a maximum of 602-616 nm, arising from the thiolate-Cu(2+) ligand to metal charge transfer, depending on the exogenous axial ligand, Cl(-) or HPO(4)(2-). The protein-Cu(2+) complex also showed unresolved small A(∥) values in the electron paramagnetic resonance (EPR) spectral analysis and a 328 mV (vs normal hydrogen electrode, NHE) redox potential with a fast electron reaction rate. The X-ray absorption spectrum revealed that the Cu(2+) coordination environment was identical to that found in natural type 1 blue copper proteins. The extended X-ray absorption fine structure (EXAFS) analysis of the protein showed two typical Cu-N(His) at around 1.9-2.0 ?, Cu-S(Cys) at 2.3 ?, and a long Cu-Cl at a 2.66 ?, which are also characteristic of the natural type 1 blue copper proteins.     

Complexes pairing hypohalous acids with nitrosyl hydride. blue shift of a NH bond that is uninvolved in a H-bond

Correlated calculations are used to analyze the interaction between nitrosyl hydride (HNO) and hypohalous acids (HOF, HOCl, and HOBr). Two minima are located on the potential energy surface of each complex, in both of which HOX acts as proton donor. Donation to the N atom of HNO makes for a more strongly bound complex, as compared to the OH..O bond in the secondary minimum. Binding energies of the global minimum are about 22 kJ/mol, as compared to 18 kJ/mol for the secondary structure; there is little sensitivity to the identity of the halogen atom. Whereas the covalent OH bond of HOX stretches and shifts to the red upon complexation, the NH bond of HNO, whether involved in a H-bond or not, behaves in the opposite manner.     

How Chemical Bonding Impacts Halide Perovskite Nanocrystals Growth to Bulk Films: Implication of Pb−X Bond on Growth Kinetics

Lead halide perovskites nanocrystals have emerged as a leading candidate in perovskite solar cells and light-emitting diodes. Given their favorable, tunable optoelectronic properties through modifying the size of nanocrystals, it is imperative to understand and control the growth of lead halide perovskite nanocrystals. However, during the nanocrystal growth into bulk films, the effect of halide bonding on growth kinetics remains elusive. To understand how a chemical bonding of Pb−X (covalency and ionicity) impact on growth of nanocrystals, we have examined two different halide perovskite nanocrystals of CsPbCl₃ (more ionic) and CsPbI₃ (more covalent) derived from the same parent CsPbBr₃ nanocrystals. Tracking the growth of nanocrystals by monitoring the spectral features of bulk peaks (at 445 nm for Cl and at 650 nm for I) enables us to determine the growth activation energy to be 92 kJ/mol (for CsPbCl₃) versus 71 kJ/mol (for CsPbI₃). The electronegativity of halides in Pb−X bonds governs the bond strength (150–240 kJ/mol), characteristics of bonding (ionic versus covalent), and growth kinetics and resulting activation energies. A fundamental understanding of Pb−X bonding provides a significant insight into controlling the size of the perovskite nanocrystals with more desired optoelectronic properties.     

Calorimetry of polymer metallization: copper,calcium, and chromium on PMDA-ODA polyimide

The heat of reaction has been measured for vapor deposition of metal atoms onto clean polymeric substrates. These calorimetric measurements introduce a new technique for the study of metal-polymer interfacial chemistry. Results for three systems are reported here, calcium, chromium, and copper on PMDA-ODA polyimide, and widely different reaction heats are observed in each case. Our results show that calcium deposition is very exothermic at low coverages, with an initial heat approaching 610 kJ/mol. In the case of chromium deposition, the initial heat is quite low, 125 kJ/mol or less, an affect we attribute to the energetic cost of polymer bond disruption. The data for copper deposition show that calorimetry can be used to study fine details of the nucleation and growth process of the metal island film.     

Molecular structure and binding energies of monosubstituted hexacarbonyls of chromium,molybdenum, and tungsten: Relativistic density functional study

Relativistic density functional calculations have been carried out for the group VI transition metal carbonyls M(CO)₅L (M=Cr, Mo, W; L=OH₂, NH₃, PH₃, PMe₃, N₂, CO, OC (isocarbonyl), CS, CH₂, CF₂, CCl₂, NO⁺). The optimized molecular structures and M(SINGLE BOND)L bond dissociation energies, as well as the metal–carbonyl bond energy of the trans CO group, have been calculated. Besides the marked dependence of the trans M(SINGLE BOND)CO bond length on the type of ligand L, such an effect on the that bond energy is also observed. For the chromium compounds, the trans Cr(SINGLE BOND)CO bond length varies from 184 to 199 pm and its bond energy from 242 to 150 kJ/mol. For the molybdenum compounds, the range is 197 to 216 pm and 253 to 128 kJ/mol and, for tungsten, 198 to 214 pm and 293 to 159 kJ/mol. The observed trends can be explained with the π acceptor strength of the L ligand. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1985–1992, 1997     

Extending, and repositioning, a thermochemical ladder: high-level quantum chemical calculations on the sodium cation affinity scale

High-level ab initio quantum chemical calculations, at the CP-dG2thaw level of theory, are reported for coordination of Na+ to a wide assortment of small organic and inorganic ligands. The ligands range in size from H to C6H6, and include 22 of the ligands for which precise relative sodium ion binding free energies have been determined by recent Fourier transform ion cyclotron resonance and guided ion beam studies. Agreement with the relative experimental values is excellent (+/-1.1 kJ mol(-1)), and agreement with the absolute scale (obtained when these relative values are pegged to the CH3NH2 "anchor" value measured in a high-pressure mass spectrometric study) is only marginally poorer, with CP-dG2thaw values exceeding the absolute experimental DeltaG(298) values by an average of 2.1 kJ mol(-1). The excellent agreement between experiment and the CP-dG2thaw technique also suggests that the additional 97 ligands surveyed here (which, in many cases, are not readily susceptible to laboratory investigation) can also be reliably fitted to the existing experimental scale. However, while CP-dG2thaw and the experimental ladder are in close accord, a small set of higher level ab initio calculations on sodium ion/ligand complexes (including several values obtained here using the W1 protocol) suggests that the CP-dG2thaw values are themselves too low by approximately 2.5 kJ mol(-1), thereby implying that the accepted laboratory values are typically 4.6 kJ mol(-1) too low. The present work also highlights the importance of Na+/ligand binding energy determinations (whether by experimental or theoretical approaches) on a case-by-case basis: trends in increasing binding energy along homologous series of compounds are not reliably predictable, nor are binding site preferences or chelating tendencies in polyfunctional compounds.     

Effects of mutations on the absorption spectra of copper proteins: a QM/MM study

The ground and excited state properties of copper proteins are studied and analyzed using hybrid quantum mechanics/molecular mechanics technique. Wild-type plastocyanin, characterized by an intense blue color, and wild-type nitrosocyanin, a red protein, are considered. These proteins differ from some ligands of the copper containing chromophore; we also studied the effects of selective mutations of one of the active site residue in plastocyanin. It is shown that this mutation is able to strongly modify the UV/VIS spectrum continuously modifying the absorption spectrum of the protein that from blue becomes red. Electrostatic and polarization effects of the macromolecular environment on the chromophore are taken into account using original techniques. Principal transitions are analyzed by mean of natural transition orbitals.