Theoretical study of copper binding to GHK peptide

We report ligand field molecular mechanics, density functional theory and semi-empirical studies on the binding of Cu(II) to GlyHisLys (GHK) peptide. Following exhaustive conformational searching using molecular mechanics, we show that relative energy and geometry of conformations are in good agreement between GFN2-xTB semi-empirical and B3LYP-D DFT levels. Conventional molecular dynamics simulation of Cu-GHK shows the stability of the copper-peptide binding over 100 ps trajectory. Four equatorial bonds in 3N1O coordination remain stable throughout simulation, while a fifth in apical position from C-terminal carboxylate is more fluxional. We also show that the automated conformer and rotamer search algorithm CREST is able to correctly predict the metal binding position from a starting point consisting of separated peptide, copper and water

Density functional dependence of molecular geometries in lanthanide(III) complexes relevant to bioanalytical and biomedical applications

[Abstract] A set of 15 lanthanide-containing model systems was used to evaluate the performance of 15 commonly available density functionals (SVWN, SPL, BLYP, G96LYP, mPWLYP, B3LYP, BH&HLYP, B3PW91, BB95, mPWB95, TPSS, TPSSh, M06, CAM-B3LYP and wB97XD) in geometry determination, benchmarked against MP2 calculations. The best agreement between DFT optimized geometries and those obtained from MP2 calculations is provided by meta-GGA and hybrid meta-GGA functionals. The use of hybrid-GGA functionals such as BH&HLYP and B3PW91 also provide reasonably good results, while B3LYP provides an important overestimation of the metal–ligand bonds. The performance of different basis sets to describe the ligand(s) atoms, as well as the use of large-core (LC) RECPs and small-core (SC) RECPs, has been also assessed. Our calculations show that SCRECP calculations provide somewhat shorter GdIII–donor distances than the LCRECP approach, the average contraction of bond distances for the systems investigated amounting to 0.033 Å. However, geometry optimizations with the SCRECP (in combination with the mPWB95 functional and the 6-31G(d) basis set for the ligand atoms) take about 15 times longer than the LC counterparts, and about four times longer than MP2/LCRECP/6-31G(d) calculations. The 6-31G(d), 6-311G(d), 6-311G(d,p) or cc-pVDZ basis sets, in combination with LCRECPs, appear to offer an adequate balance between accuracy and computational cost for the description of molecular geometries of LnIII complexes. Electronic energies calculated with the the cc-pVxZ family (x = D-6) indicate a relative fast convergence to the complete basis set (CBS) limit with basis set size. The inclusion of bulk solvent effects (IEFPCM) was shown to provoke an important impact on the calculated geometries, particularly on the metal–nitrogen distances. Calculations performed on lanthanide complexes relevant for practical applications confirmed the important effect of the solvent on the calculated geometries.Ministerio de Educación y Ciencia; CTQ2009-10721Xunta de Galicia; IN845B-2010/06

Structural diversity in tetrakis(4-pyridyl)porphyrin supramolecular building blocks

The authors would like to thank the University of Alabama Department of Chemistry and the University of Missouri-Columbia Department of Chemistry for support of this work.In memory of a pioneer in crystal engineering, Prof. Israel Goldberg, we report a series of new framework solids, based on the ligand tetrakis(4–pyridyl)porphyrin (TPyP). Spontaneous reactions of TPyP with seven different metal salts under liquid-liquid diffusion at ambient temperature show that the formation of ionic compounds is preferred to coordination polymers due to increased conformational freedom. Two coordination networks, {(HgI2)2(TPyP)}n·4nCHCl3∙2nTCE (TCE = 1,1,2,2–tetrachloroethane), and {(Ba(μ1,1–NCS)(μ1,1,3–NCS)(H2O)(MeCN))2(TPyP)}n·4nH2O, displayed a new isomeric form of the known [(HgI2)2(TPyP)]∞ polymeric motif, and a two-dimensional honeycomb polymeric motif linked by hydrogen-bonding into a three dimensional moganite (mog) net, respectively. Four protonated porphyrinic salts, [H3TPyP][PF6]3∙0.5TCE, [H2TPyP][I3]2·2MeOH, [H4TPyP][UO2Cl4]2·6MeCN, and [H4TPyP][Th(NO3)6][NO3]2, were observed which hydrogen bond to give one- or two-dimensional networks, or in the case of [H4TPyP][UO2Cl4]2·6MeCN, a discrete dinuclear hydrogen-bonded complex. In one case, a neutral, hydrogen-bonded complex, Ce(NO3)3(MeOH)3(H2O)·TPyP·TCE·H2O, was formed which adopts a three-dimensional, self-penetrated variant of the face-centered cubic (fcc) network. These new structures represent hybrid organic-inorganic crystalline compounds in which the multidentate porphyrin units, having both hydrogen bonding, as well as coordination functionalities, are interlinked through the inorganic connectors into self-assembled three-dimensional architectures. This work shows the relative stability of noncovalently bound vs. coordination networks as well as the effective potential of the TPyP building block to construct supramolecular assemblies in the presence or absence of coordinating ions as linkers.PostprintPeer reviewe

カガク ケツゴウ ノ デンシ ジョウタイ ニ カンスル リロンテキ ケンキュウ

Kyoto University (京都大学)0048新制・課程博士博士(工学)甲第14161号工博第2995号新制||工||1444(附属図書館)26467UT51-2008-N478京都大学大学院工学研究科マイクロエンジニアリング専攻(主査)教授 立花 明知, 教授 榊 茂好, 教授 木村 健二学位規則第4条第1項該

ab initio Molecular Dynamics Simulations of Storage Pond Radionuclides and Related ions

An important problem in the nuclear power industry in the UK is the reprocessing of the legacy waste storage ponds at Sellafield in Cumbria. Understanding the solvation structure of the ions present in these ponds, as well as the stability of their hydroxide complexes, is vital for effective clean-up. This work used ab initio molecular dynamics (AIMD) to characterise the solvation structure of Mg2+, Ca2+, Sr2+, Cs+, U6+ in the form of uranyl (UO22+), La3+ and Lu3+. These ions have been found in the legacy storage ponds and have previously been studied through gas phase or implicit solvation Density Functional Theory (DFT) methods. The properties of the first solvation shell have been categorised, and when compared to current experimental and computational literature the results are in excellent agreement, justifying the solvation model developed. The understanding of the solvation structure of the ions in the storage ponds has been developed further, with the introduction of hydroxide ions to replicate the storage ponds alkaline conditions. The coordination and bonding of the hydroxide complexes was characterised, as was the proton transfer behaviour, through quantifying the Proton Transfer Events (PTEs) of each system. The introduction of hydroxides generally led to reduction in coordination number and bond length of the first solvation shell. It was found that PTEs were more prevalent away from the central ion of the system and occurred more frequently in the less charge dense ionic systems, where direct hydroxide coordination to the ion is less prevalent. The final focus of the work was a DFT examination of the adsorption of Sr2+ onto a solvated CeO2(111) surface. The results showed a preference for some ion coordination to the surface, which lessened when hydroxide ions were introduced to the solvation model. The aim of this chapter was to investigate the validity of the surface-solvation model using a surface relevant to the nuclear waste disposal problem for use in future AIMD simulations of the fuel pond environment

Exploration of the effect of metal-ions interaction on biomolecular systems

Herein, complexes of amyloid-β (1-16) monomer with physiologically relevant metal cations such as zinc, iron, and copper, have been analysed using density functional theory DFT, semiempirical GFN2-xTB, and molecular mechanics methods. A short peptide (GHK) bound to copper was used as a model for examination of method efficacy. The semiempirical method under review was shown to reproduce the DFT energy and geometry obtained with ligand field molecular mechanics (LFMM). This made it then appropriate for further application on three different fragmentation lengths of Aβ-16 bonded to Cu(II). Accelerated molecular dynamics (aMD) simulations with the AMBER14SB force field were used to simulate the free and metal-bound Aβ-16 peptide with Zn(II), Fe(II), and Cu(II), through different binding modes. The simulation showed all metals stabilized the peptide mobility and increased the compactness in terms of RMSD, Rg, and RMSF, compared to that in the unbound monomer. The most frequent salt bridge interaction in all metal-Aβ forms, was found between Arg5 and Asp7 amino acids. The aMD simulations also showed that the number of coordinating atoms, as well as the element and/or residues, influence the overall structure, size, and stability. The observation of α-sheet secondary structure in Aβ simulations led us to extend the study to different proteins that have been reported to have this uncommon structure, also related to Aβ aggregation. DFT and semiempirical GFN2-xTB calculations were used on the modelled α�sheet residues of the peptides. The α-helix is the most stable form, compared to α-sheet and β-strand conformations, in most cases. However, in the example of peptide 1E9T, the α-sheet presents the most stable form overall, and the stability increased in the existence of cationic ions influenced mainly by the ionic charge and radius of the bound ions. Mg2+ and Ca2+ have the greatest effect on the relative stability followed by K+ , Na+ and Li+ . MD was performed on full length 1E9T peptide in a range of pH and at 310 and 498 K, in explicit solvent, with and without KCl ions. The results were consistent with literature in which α-sheet structure is a transient state between α-helix and β-sheet formation

Elucidating the Electronic Origins of Intermolecular Forces in Crystalline Solids

It is not possible to study almost any physical system without considering intermolecular forces (IMFs), no matter how insignificant they may appear relative to other energetic factors. Countless studies have shown that IMFs are responsible for governing a wide variety of physical properties, but often the atomic-origins of such interactions elude experimental detection. A considerable amount of work throughout the course of this research was therefore placed on using quantum mechanical simulations, specifically density functional theory (DFT), to calculate the electronic properties of solid-materials. The goal of these calculations was a better understanding of the precise origins of interatomic energies, down to the single-electron level. Furthermore, experimental X-ray diffraction and terahertz spectroscopy were both utilized because they are able to broadly probe the potential energy surfaces of molecular crystals, enhancing the theoretical data. Combining DFT calculations with experimental measurements enabled in-depth studies into the nature of specific non-covalent interactions, with results that were often unexpected based on conventional descriptions of IMFs. Overall, this work represents a significant advancement in understanding how subtle changes in characteristics like orbital occupation or electron density can have profound effects on bulk properties, highlighting the fragile relationship that exists between the numerous energetic parameters occurring within condensed phase systems

Nah-Infrarot Cr(III)- und V(III)-Luminophore: Multiphonon Relaxation und Upconversion-Lumineszenz

Diese Arbeit befasst sich mit der Konzeption, Darstellung und photophysikalischen Charakterisierung von neuen lumineszenten Materialien auf Basis der 3d-Übergangsmetalle Vanadium und Chrom. Dabei konnte das Konzept von bekannten Chrom(III)-Komplexen mit Spin-Flip- Emission auf Metallkomplexe des günstigen und reichlich verfügbaren Metalls Vanadium erweitert werden. Der neu entwickelte [V(ddpd)2](PF6)3-Komplex (ddpd = N,N’-dimethyl-N,N’-dipyridin-2-ylpyridin-2,6-diamin) ist dabei der erste 3dn-Metallkomplex (n ≠ 10) überhaupt, welcher NIR-Lumineszenz oberhalb von 1000 nm bei Raumtemperatur und in Lösung zeigt. Weiter wurden ausführliche Studien zu Multiphonon Relaxation (MR) bei Chrom(III)- und Vanadium(III)-Spin-Flip-Emittern durchgeführt. MR bezeichnet die strahlungslose Deaktivierung der angeregten, emittierenden Metallzustände durch Energietransfer auf Schwingungsobertöne von hochenergetischen Oszillatoren wie beispielsweise O-H-, N-H- oder C-H-Streckschwingungen der Liganden oder des Lösungsmittels. An selektiv deuterierten Liganden und der entsprechenden lumineszenten Chrom(III)- Komplexe konnten erstmals die Obertonsignaturen einzelner aromatischer C-H-Oszillatoren aus gemessenen Obertondaten ermittelt und so die Beiträge spezifischer aromatischer C-H-Oszillatoren des Liganden zur MR beurteilt werden. Zusätzlich wurde der Einfluss von Multiphonon Relaxation auf die Photophysik von neuen Chrom(III)- und Vanadium(III)-Emittern untersucht. Darüber hinaus wurden im Rahmen dieser Arbeit neue photoaktive heterometallische Chrom-Lanthanoid-Architekturen entwickelt, aufgebaut aus einfach zugänglichen Cr3+- und Ln3+-Komplexionen. Durch Überarbeitung früherer Cr3+/Yb3+-Systeme konnte ein neuer molekularer Festkörper realisiert werden, welcher NIR→NIR-Upconversion Lumineszenz in der Gegenwart von Sauerstoff und Wasser zeigt. Des Weiteren wurden die Lumineszenzeigenschaften weiterer Chrom-Lanthanoid-Salze charakterisiert und die zugrundeliegenden Energietransferprozesse zwischen den Metallzentren untersucht