Quantum mechanical study of transition metal hydrides: Comparison of determined molecular properties with experimental data.

This study compares results of four relativistic pseudopotential basis sets, which differ mainly by their size: double-zeta introduced by Hay and Wadt from Los Alamos National Laboratory (LANL2DZ), triple-zeta based on Stuttgart energy-consistent scalar-relativistic pseudopotential (SDD3), its extension with 2fg polarization functions, and combination of Stuttgart pseudopotentials with quintuple-zeta cc-pV5Z base (SDD5). Hydrides of transition metals from Cr to Zn group are chosen as reference molecules. The coupled cluster method (CCSD(T)) is used for evaluation of selected molecular characteristics. Interatomic distances, dissociation energies, vibration modes, and anharmonicity constants are determined and compared with available experimental data. As expected, the accuracy of basis depends mainly on its size. However, only moderate modification of SDD3 basis set significantly improves its accuracy, which becomes comparable to the largest basis set. Nevertheless, the time consumption is significantly lower.

Determination of Amino Acids' pKa: Importance of Cavity Scaling within Implicit Solvation Models and Choice of DFT Functionals.

Protonation states of molecules significantly influence the thermodynamics and kinetics of chemical reactions. This is especially important in biochemical processes, where appropriate protonation states of amino acids control the exo/endoergicity of practically all biochemical cycles. This paper is focused on appraisal of the impact of DFT functionals and PCM solvation models on the accuracy of pKa evaluations for all proteinogenic amino acids. Eight functionals (B3LYP, PBE0, revPBE0, M06-2X, M11, M11-L, TPSSh, and ωB97X-D) and four basis sets are considered, together with four kinds of implicit solvation models when additional attention is paid to a cavity construction. An influence of nonelectrostatic contributions and Wertz's corrections on Gibbs free energy is investigated together with accuracy of provided proton solvation energy. The best model is based on the M06-2X/6-311++G**/D-PCM/UAKS computational level. The fitting procedure is utilized to improve the accuracy of the evaluated models. All of these results are also compared with values obtained from the COSMOtherm program and CCSD(T) calculations. Results for cysteine and histidine are discussed individually, as they can be found in different protonation states at neutral pH.

Vertical Excitation Energies and Lifetimes of the Two Lowest Singlet Excited States of Cytosine, 5-Aza-cytosine, and the Triazine Family: Quantum Mechanics-Molecular Mechanics Studies.

A swarm of semi-classical quantum mechanics/molecular mechanics molecular-dynamics simulations where OM2/MNDO is combined with the Gromacs program for consideration of explicit water is performed, solving the time-dependent Schrödinger equation in each step of the trajectories together with the Tully's fewest switches algorithm. Within this stochastic treatment, time dependent probabilities of the three lowest electronic states are determined. The fact that nucleobases are quickly deactivated is confirmed in the cytosine case where our best lifetime estimation is τ1=0.82 ps for the model with 100 water molecules with the SPCE force field and a time step of 0.1 fs. Lifetimes of the remaining molecules are visibly longer: 5-azacytosine, 2,4-diamino-1,3,5-triazine (DT), and 2,4,6-triamino-1,3,5-triazine (TT) molecules have an S1 → S0 de-excitation time of slightly above 10 ps. The lifetimes of the triazine family increases with the increasing number of exocyclic amino groups, that is, s-triazine < 2-amino-1,3,5-triazine < DT < TT. This can be explained by a higher mobility of the carbon-bonded hydrogen atoms in comparison with heavier amino groups since their movement is slowed down due to a substantially higher mass than hydrogen atoms, which can easier reach the out-of-plane positions required in the conical intersection structures. Moreover, bulkier NH2 ligands suffer due to greater friction caused by the surrounding water environment. These mechanical aspects caused a change in the explored lifetime dependences in comparison with our previous gas-phase study.

The vertical excitation energies and a lifetime of the two lowest singlet excited states of the conjugated polyenes from C2 to C22: Ab initio, DFT, and semiclassical MNDO-MD simulations.

Electronic excited states in the series of polyene molecules were explored. Optimal ground-state geometry was used for the evaluation of vertical excitation energies. Results of a chosen set of functionals were compared to post-HF methods (EOM-CCSD, NEVPT2, CASPT2, and MRCI). In addition, the semiempirical OM2/MNDO method using MRCISD computational level was confronted with the above-mentioned techniques. Despite the fact that the first excited state has a significant double-excitation character some functionals were able to qualitatively determine the correct state order (where the lowest excited state has a A g - character). The most successful functionals in transition energies predictions were PBE, TPSS and BLYP in Tamm-Dancoff approach (TDA), which had the smallest root-mean-square deviation (RMSD) scoring towards the experimental values. Regarding RMSD scoring, the OM2/MNDO method performed fairly well, too. Besides absorption spectra, lifetimes of the first two excited states were estimated based on a stochastic approach exploring a swarm of OM2/MNDO hopping dynamics using the Tully fewest switch algorithm for each molecule. The longest lifetime of the first excited state (S1 ) was found for decapentaene (about 5 ps). Further elongation of the conjugated chain caused a mild decrease of this value to ca 1.5 ps for docosaundecaene.

QM and QM/MM umbrella sampling MD study of the formation of Hg(II)-thymine bond: Model for evaluation of the reaction energy profiles in solutions with constant pH.

The formation of the Hg-N3(T) bond between the 1-methylthymine (T) molecule and the hydrated Hg2+ cation was explored with the combined quantum mechanics/molecular mechanics (QM/MM) method including Free Energy Perturbation corrections. The thermodynamic properties were determined in the whole pH range, when these systems were explicitly investigated and considered as the QM part: (1) T + [Hg(H2 O)6 ]2+ , (2) T + [Hg(H2 O)5 (OH)]+ , (3) T + Hg(H2 O)4 (OH)2 , and (4) N3-deprotonated T + Hg(H2 O)4 (OH)2 . The MM part contained only solvent molecules and counterions. As a result, the dependence of Gibbs-Alberty reaction free energy on pH was obtained along the reaction coordinate. We found that an endoergic reaction in acidic condition up to pH < 4-5 becomes exoergic for a higher pH corresponding to neutral and basic solutions. The migration of the Hg2+ cation between N3 and O4/2 positions in dependence on pH is discussed as well. For the verification, DFT calculations of stationary points were performed confirming the qualitative trends of QM/MM MD simulations and NMR parameters were determined for them.

A Dogma in Doubt: Hydrolysis of Equatorial Ligands of PtIV Complexes under Physiological Conditions.

Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, PtIV complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato PtIV complexes was studied under physiologically relevant conditions. Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes underwent fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the resulting hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for the activation of PtIV drugs, which also changes the anticancer potential of the compounds in cell culture. The discovery that intact PtIV complexes can hydrolyze at equatorial position contradicts the dogma on the general kinetic inertness of PtIV compounds and needs to be considered in the screening and design for novel platinum-based anticancer drugs.

Square-Planar Pt(II) and Ir(I) Complexes as the Lewis Bases: Donor-Acceptor Adducts with Group 13 Trihalides and Trihydrides.

The stability and properties of donor-acceptor adducts of square-planar Pt(II) and Ir(I) complexes (designated as PtX, IrX, or generally MX complexes) with trihydrides and trihalides of group 13 elements of general formula YZ3 (Y = B, Al, Ga; Z = H, F, Cl, Br) were studied theoretically using DFT methodology in the gas phase. MX complexes were represented by wide range of the ligand environment which included model complexes [Ir(NH3)3X]0 and cis-[Pt(NH3)2X2]0 (X = H, CH3, F, Cl, Br) and isoelectronic complexes [Ir(NNN)(CH3)]0 and [Pt(NCN)(CH3)]0 with tridentate NNN and NCN pincer ligands. MX complexes acted as the Lewis bases donating electron density from the doubly occupied 5d z2 atomic orbital of the metal M atom to the empty valence p z orbital of Y whose evidence was clearly provided by the natural atomic orbital (NAO) analysis. This charge transfer led to the formation of pentacoordinated square pyramidal MX·(YZ3) adducts with M·Y dative bond. Binding energies were -44.7 and -75.2 kcal/mol for interaction of GaF3 as the strongest acid with PtNCN and IrNNN pincer ligands complexes. Only M·B bonds had covalent character although MX·BZ3 adducts were the least stable due to large values of Pauli repulsion and deformation energies. The highest degree of covalent character was found for adducts of BH3 in all series of structures studied. Al and Ga adducts showed remarkably similar behavior with respect to geometry and binding energies.

Correction to: Exploration of selected electronic characteristics of half-sandwich organoruthenium(II) ß-diketonate complexes.

We would like to apologize for a wrong conclusion on the fourth page where the correlation of the Ru-P bond length and possible anticancer activity is discussed.

Protein environment affects the water-tryptophan binding mode. MD, QM/MM, and NMR studies of engrailed homeodomain mutants.

Water molecules can interact with aromatic moieties using either their O-H bonds or their lone-pairs of electrons. In proteins, water-π interactions have been reported to occur with tryptophan and histidine residues, and dynamic exchange between O-Hπ hydrogen bonding and lone-pairπ interactions was suggested to take place, based on ab initio calculations. Here we used classical and QM/MM molecular dynamics simulations, complemented with an NMR study, to examine a specific water-indole interaction observed in the engrailed homeodomain and in its mutants. Our simulations indicate that the binding mode between water and indole can adapt to the potential created by the surrounding amino acids (and by the residues at the DNA surface in protein-DNA complexes), and support the model of dynamic switching between the O-Hπ hydrogen bonding and lone-pairπ binding modes.

Exploration of selected electronic characteristics of half-sandwich organoruthenium(II) ß-diketonate complexes.

Based on experimental work, 12 half-sandwich organoruthenium(II) complexes with p-cymene and various substituted ß-diketonates (acac) modified by several functional groups were explored. These complexes were optimized at the B3PW91/6-31 + G(d)/PCM/UFF computational level with the Ru atom described by Stuttgart pseudopotentials. The electron density analysis was performed using the B3LYP/ 6-311++G(2df,2pd)/DPCM/scaled-UAKS model. Electrostatic and averaged local ionization potential were explored and extremes on 0.001 e/a.u.3 isodensity surfaces discussed. Natural population analysis partial charges and electron densities in bond critical point of the key Ru(II) coordination bonds were determined. There was a clear correlation between the results obtained and experimentally known anticancer descriptors. Graphical abstract Top Average local ionization potential (ALIP) of half-sandwich organoruthenium(II) ß-diketonate complex, bottom IC 50 of b-series for ovarian cancer and Ru-P distances (in Å).

Formation of chelate structure between His-Met dipeptide and diaqua-cisplatin complex; DFT/PCM computational study.

Interaction of cisplatin in activated diaqua-form with His-Met dipeptide is explored using DFT approach with PCM model. First the conformation space of the dipeptide is explored to find the most stable structure (labeled 0683). Several functionals with double-zeta basis set are used for optimization and obtained order of conformers is confirmed by the CCSD(T) single-point calculations. Supermolecular model is used to determine reaction coordinate for the replacement of aqua ligands consequently by N-site of histidine and S-site of methionine and reversely. Despite the monoadduct of Pt-S(Met) is thermodynamically less stable this reaction passes substantially faster (by several orders of magnitude) than coordination of cisplatin to histidine. The consequent chelate formation occurs relatively fast with energy release up to 12 kcal mol-1.

Redox Potentials for Tetraplatin, Satraplatin, Its Derivatives, and Ascorbic Acid: A Computational Study.

Redox potentials of the Pt(IV) complexes, such as satraplatin, tetraplatin, and several others, are determined at the density functional theory (DFT) level (with B3LYP, ω-B97XD, PBE1PBE, TPSSTPSS, M06-L, M11-L, and MN12-L functionals) and compared with post-Hartree-Fock methods MP2 and CCSD(T). Calculations are performed in water solution employing an implicit solvation model. The impact of replacement of a chloro ligand by a water molecule (hydration in the equatorial plane of the complexes) is also explored. Furthermore, an influence of solvent pH on the magnitude of the redox potentials is discussed for such hydrated complexes. The obtained results are compared with available experimental data leading to a root-mean-square deviation (RMSD) of ca. 0.23 V, using the CCSD(T)/6-31+G(d)/IEF-PCM/scaled-UAKS level. Distribution of the electron density is analyzed at the B3LYP/6-311++G(2df,2pd) level. Also, a correlation between binding energies of axial ligands and the redox potential is demonstrated. Since the Pt(IV) complexes are considered in the framework of anticancer treatment, possible reducing agents in bioenvironment are searched. From this reason, the reduction potential of different protonation states of ascorbic acid is also presented.

The influence of the metal cations and microhydration on the reaction trajectory of the N3 ↔ O2 thymine proton transfer: Quantum mechanical study.

This study involves the intramolecular proton transfer (PT) process on a thymine nucleobase between N3 and O2 atoms. We explore a mechanism for the PT assisted by hexacoordinated divalent metals cations, namely Mg2+ , Zn2+ , and Hg2+ . Our results point out that this reaction corresponds to a two-stage process. The first involves the PT from one of the aqua ligands toward O2. The implications of this stage are the formation of a hydroxo anion bound to the metal center and a positively charged thymine. To proceed to the second stage, a structural change is needed to allow the negatively charged hydroxo ligand to abstract the N3 proton, which represents the final product of the PT reaction. In the presence of the selected hexaaqua cations, the activation barrier is at most 8 kcal/mol. © 2017 Wiley Periodicals, Inc.

Study on electronic properties, thermodynamic and kinetic parameters of the selected platinum(II) derivatives interacting with guanine.

Interaction of hydrated forms of several potential anticancer agents (PtCl2(diaminocyclohexane), trans-[PtCl2(NH3)(thiazole)], cis-[PtCl2(NH3)(piperidine)], and cis-PtCl2(NH3)(cyclohexylamine) complexes) with guanine are explored and compared with an analogous interaction of cisplatin. Basic electronic properties, binding and stabilization energies are determined and energy profiles for the aquation reaction are estimated at the B3LYP/6-311++G(2df,2pd) level of theory. It is found that the substitution reaction is an exothermic and exergonic process with ΔG slightly less negative than -20kcal/mol. The largest energy release occurs for PtCl(H2O)(diaminocyclohexane) complex. The rate constants for the Pt(II) complexes in the chloro- and hydroxo-form are compared and an impact of the ligand in the trans position to water is discussed.

Side Reactions with an Equilibrium Constraint: Detailed Mechanism of the Substitution Reaction of Tetraplatin with dGMP as a Starting Step of the Platinum(IV) Reduction Process.

Two possible pathways of the substitution reaction within the reduction process of the PtIV(DACH)Cl4 by dGMP are compared: associative reaction course and autocatalytic Basolo-Pearson mechanisms. Since two forms: single-protonated and fully deprotonated phosphate group of dGMP are present in equilibrium at neutral and mildly acidic solutions, consideration of a side reactions scheme with acido-basic equilibrium-constraint is a very important model for obtaining reliable results. The examined complexes are optimized at the B3LYP-GD3BJ/6-31G(d) level with the COSMO implicit solvation model and Klamt's radii used for cavity construction. Energy characteristics and thermodynamics for all reaction branches are determined using the B3LYP-GD3BJ/6-311++G(2df,2pd)/IEF-PCM/scaled-UAKS level with Wertz's entropy corrections. Rate constants are estimated for each individual branch according to Eyring's transition state theory (TST), averaged according to equilibrium constraint and compared with available experimental data. The determined reaction barriers of the autocatalytic pathway fairly correspond with experimental values. Furthermore, autocatalytic reaction of tetraplatin and its two analogues complexes [PtIV(en)Cl4 and PtIV(NH3)2Cl4] are explored and compared with measured data in order to examined general reaction descriptors.

Estimation of Transition-Metal Empirical Parameters for Molecular Mechanical Force Fields.

Force-field parameters of the first row transition metals together with a few additional common elements such as those from the second (Rh, Ru) and third (Hg, Pt) rows of elements in ligated forms were determined based on the density functional theory calculations. Bonding characteristics were determined by averaging metal-ligand force constants in optimal geometries from several chosen complexes of each metal in the most common oxidation numbers and structural arrangements. Parameters of Lennard-Jones potential were determined based on a supermolecular model. Our determined molecular mechanical parameters are compared with presently available parameters published by other groups. We performed two different kinds of testing in order to demonstrate the reliability of these parameters in the case of ligated metallo complexes. First, the nonbonding potential was constructed for an additional set of 19 larger systems containing common complexes with organic molecules. The second test compares the Pt-O and Pt-H radial distribution functions for cisplatin in a box of TIP3P water with lately published studies.

Interactions of the "piano-stool" [ruthenium(II)(η(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study.

Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ∼6 kcal/mol) in basic environment. © 2016 Wiley Periodicals, Inc.

Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study.

The reduction mechanism of [Pt(IV) (dach)Cl4 ] (dach=diaminocyclohexyl) in the presence of dGMP was studied. The first step is substitution of a chloro ligand by dGMP, followed by nucleophilic attack of a phosphate or sugar oxygen atom to the C8-position of guanine. Subsequent reduction forms the [Pt(II) (dach)Cl2 ] complex. The whole process is completed by a hydrolysis. Two different pathways for the substitution reaction were examined: a direct associative and a Basolo-Pearson autocatalytic mechanism. All the explored structures were optimized at the B3LYP-D3/6-31G(d) level and by using the COSMO solvation model with Klamt's radii. Single-point energetics was determined at the B3LYP-GD3BJ/6-311++G(2df,2pd)/PCM/scaled-UAKS level. Activation barriers were used for an estimation of the rate constants and these were compared with experimental values. It was found that the rate-determining step is the nucleophilic attack with a slightly faster performance in the 3'-dGMP branch than in the case of 5'-dGMP with activation barriers of 21.1 and 20.4 kcal mol(-1) (experimental: 23.8 and 23.2 kcal mol(-1) ). The reduction reaction is connected with an electron flow from guanine. The product of the reduction reaction is a chelate structure, which dissociates within the last reaction step, that is, a hydrolysis reaction. The whole redox process (substitution, reduction, and hydrolysis) is exergonic by 34 and 28 kcal mol(-1) for 5'-dGMP and 3'-dGMP, respectively.

A double-QM/MM method for investigating donor-acceptor electron-transfer reactions in solution.

We developed a double-quantum mechanical/molecular mechanical (d-QM/MM) method for investigation of full outer-sphere electron transfer (ET) processes between a donor and an acceptor (DA) in condensed matter. In the d-QM/MM method, which employs the novel concept of multiple QM regions, one can easily specify the number of electrons, spin states and appropriate exchange-correlation treatment in each QM region, which is especially important in the cases of ET involving transition metal sites. We investigated Fe(2+/3+) self-exchange and Fe(3+) + Ru(2+) → Fe(2+) + Ru(3+) in aqueous solution as model reactions, and demonstrated that the d-QM/MM method gives reasonable accuracy for the redox potential, reorganization free energy and electronic coupling. In particular, the DA distance dependencies of those quantities are clearly shown at the density functional theory hybrid functional level. The present d-QM/MM method allows us to explore the intermediate DA distance region, important for long-range ET phenomena observed in electrochemistry (on the solid-liquid interfaces) and biochemistry, which cannot be dealt by the half-reaction scheme with the conventional QM/MM.

Energy transfer in aggregates of bacteriochlorophyll c self-assembled with azulene derivatives.

Bacteriochlorophyll (BChl) c is the main light-harvesting pigment of certain photosynthetic bacteria. It is found in the form of self-assembled aggregates in the so-called chlorosomes. Here we report the results of co-aggregation experiments of BChl c with azulene and its tailored derivatives. We have performed spectroscopic and quantum chemical characterization of the azulenes, followed by self-assembly experiments. The results show that only azulenes with sufficient hydrophobicity are able to induce aggregation of BChl c. Interestingly, only azulene derivatives possessing a conjugated phenyl ring were capable of efficient (∼50%) excitation energy transfer to BChl molecules. These aggregates represent an artificial light-harvesting complex with enhanced absorption between 220 and 350 nm compared to aggregates of pure BChl c. The results provide insight into the principles of self-assembly of BChl aggregates and suggest an important role of the π-π interactions in efficient energy transfer.