A comparative study of semiempirical, ab initio, and DFT methods in evaluating metal-ligand bond strength, proton affinity, and interactions between first and second shell ligands in Zn-biomimetic complexes

International audienceAlthough theoretical methods are now available which give very accurate results, often comparable to the experimental ones, modeling chemical or biological interesting systems often requires less demanding and less accurate theoretical methods, mainly due to computer limitations. Therefore, it is crucial to know the precision of such less reliable methods for relevant models and data. This has been done in this work for small zinc-active site models including O- (H2O and OH-) and N-donor (NH3 and imidazole) ligands. Calculations using a number of quantum mechanical methods were carried out to determine their precision for geometries, coordination number relative stability, metal–ligand bond strengths, proton affinities, and interaction energies between first and second shell ligands. We have found that obtaining chemical accuracy can be as straightforward as HF geometry optimization with a double-f plus polarization basis followed by a B3LYP energy calculation with a triple-f quality basis set including diffuse and polarization functions. The use of levels as low as PM3 geometry optimization followed by a B3LYP single-point energy calculation with a double-tzeta quality basis including polarization functions already yields useful trends in bond length, proton affinities or bond dissociation energies, provided that appropriate caution is taken with the optimized structures. The reliability of these levels of calculation has been successfully demonstrated for real biomimetic cases

Development of Semiempirical Models for Metalloproteins

Theoretical models and computational techniques are useful for gaining insight into the interactions, movements, and functions of atoms and molecules, ranging from small chemical systems with few atoms to large biological molecules with many atoms. Due to the inability of force field methods to accurately describe different properties of metalloenzymes and the prohibitive computing cost of high-level quantum methods, computationally efficient models are needed. This dissertation describes the development of new quantum semiempirical models for metalloproteins. The original AM1 (Austin Model 1) based on the neglect of diatomic differential overlap approximations was re-parameterized to describe the structural and energetic properties of biomolecules that mimic the active sites of metalloproteins. The biologically inspired genetic algorithm PIKAIA was used to optimize the parameters for each chemical element. Structures and energies of various clusters analogous to complexes found in metalloproteins were prepared as a training set using hybrid density functional theory. Models were trained to reproduce all of the properties included in the small training set. The optimized models were validated for large testing sets that incorporate bigger complexes and related reactions. Finally, the optimized models were used to study biologically-relevant processes in condensed phase using molecular dynamics simulations. All the gas- and liquid-phase results from the optimized models were compared with original semiempirical models as well as available high-level theoretical and experimental results. Metal ions play crucial roles in biological systems. They actively participate in structural, catalytic, and co-catalytic activities of a large number of enzymes. The development of semiempirical models is divided into three parts. First, new AM1 parameters for hydrogen and oxygen were developed to describe gas-phase proton transfer reactions in water and static and dynamic properties of liquid water. Gas-phase results were compared with original AM1, RM1, and PM3 models, whereas liquid results were compared with original AM1, AM1-W, and AM1PG-W models, and with available experimental results. It is found that the optimized model reproduces experimental data better than other available semiempirical models. Second, using the previously optimized model for hydrogen and oxygen, the AM1 model is re-parameterized for zinc and sulfur to describe important physical and chemical properties of zinc, water, hydrogen sulfide complexes mimicking structural motifs found in zinc enzymes. Metal-induced pKa shifts are computed for water and hydrogen sulfide, and compared with available theoretical and experimental results. Third, using previously optimized parameters for hydrogen, oxygen, and zinc, AM1 parameters for carbon and nitrogen are optimized to study proton transfer, nucleophilic attacks, and peptide hydrolysis mechanisms in zinc metalloproteases. Overall, the optimized models give promising results for the various properties of biomolecules in gas-phase clusters and in condensed phase. Particularly, the water model reproduces the proton transfer related properties in gas-phase and the structure, dielectric properties, and infrared spectra of liquid water. The zinc/sulfur model reproduces the hydration structure of zinc cation and zinc-bound hydrogen sulfide. Results for the coordination configurations of zinc solvated in water and in hydrogen sulfide confirm the versatility of the model. The optimized model for carbon and nitrogen improves the overall performance compared to AM1 and PM3. The optimized model for carbon and nitrogen reproduces structures and various energetic terms for zinc-ligands systems (representing the active sites of zinc enzymes) when compared to density functional theory results. The optimized model can be used to study metal-ligand reactivity in zinc enzymes

Mixed Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulations of Biological Systems in Ground and Electronically Excited States

The current state of the art of Quantum Mechanical/molecular mechanical (QM/MM) molecular dynamics approaches in ground and electronically excited states and their applications to biological problems is reviewed. For a complete description of quantum phenomena, the quantum nature of both electrons and nuclei has to be taken into account. Most of the current QM/MM applications are based on adiabatic dynamics in the electronic ground state. However, for dynamics in electronically excited states, the coupling between states, which is mediated via the nuclear motion, can be sizable, and nonadiabatic effects have to be taken into account. Configuration Interaction Singles (CIS) is a popular method in QM/MM applications due to its computational expedience that allows for the treatment of several hundred atoms. Since the 1990s, the Modified Neglect of Differential Overlap (MNDO) method has been further extended to a d orbital basis. This MNDO/d extension allows for the treatment of heavier elements. By using feature selection algorithms348 to identify the most appropriate subset of relevant variables that describe a certain phenomenon, the high-dimensionality of QM/MM data can be reduced and used for further analysis with causal inference algorithms to establish unique cause-effect relationships

Теорија Функционала Густине у проучавању електронских стања аква- и оксо- комплекса прве серије прелазних метала

In the scope of present doctoral thesis, the complicated electronic structure of aqua- and oxo- complexes of the first row transition metals is studied. Energies of the ground and excited electronic states of transition metal complexes are calculated using DFT-based theoretical methods. The performance of different DFAs was investigated in order to find an unambiguous way to determine the ground spin state of oxo- and hydroxo-iron complexes, which is one of the most demanding tasks, both from theoretical and experimental point of view. The results direct us to use S12g for optimization as well as for the determination of the ground spin state.For calculation of excited states, two different methods (TD-DFT and LF-DFT) are utilized, whereas the results are rationalized and compared with those obtained experimentally. The results indicate a significantly better performance of LF-DFT method for calculation of excited states and reproduction of experimental spectra. In addition, EDA study of a series of oxo- and hydroxo- iron model complexes was performed. The binding energy is decomposed into chemically meaningful contributions. Obtained results show that the most important factor, responsible for the energy differentiation, is the destabilizing preparation energy based on excitation energy requirements and oxidation state of the metal. And the other is the stabilizing orbital interaction energy established when chemical bonds are created. The primary challenge was to establish an appropriate level of theory able to explain the relationships between structural features and electronic structure, and in turn rationalize the experimentally obtained results. The scientific content of this dissertation proposes computational steps which make DFT reliable for explaining, interpreting and predicting the characteristics and properties of first row transition metal complexes. By rationally applying the proposed methodologies, we have an exclusive opportunity to clarify the experimental blindspots and apply the basic principles in order to understand the chemical complexities.У оквиру ове докторске тезе проучавана је компликована електронска структура аква- и оксо- комплекса прве серије прелазних метала. Теоријским методама, заснованим на DFT, израчунате су енергије основних и побуђених електронских стања комплекса прелазних метала. Испитано је понашање различитих DFA у циљу проналажења недвосмисленог начина за одређивање основног спинског стања оксо- и хидроксо- комплекса гвожђа, што је захтевaн задатак, и са теоријског и са експерименталног становишта. Резултати нас усмеравају на коришћење S12g за оптимизацију, као и за одређивање основног спинског стања. За рачунање побуђених стања употребљене су две различите методе (TD-DFT и LF-DFT) а резултати рационализовани и упоређени са експериментално добијеним. Резултати указују на знатно боље понашање LF-DFT методе за рачунање побуђених стања и репродукцију експерименталних спектара. У склопу ове дисертације изведено је и EDA изучавање серије оксо- и хидроксо- модел комплекса гвожђа. Енергија везивања разложена је на хемијски смислене доприносе. Резултати показују да је најбитнији фактор, одговоран за енергетску диференцијацију енергија побуђивања, неопходна да се метални јон из изолованог електронског стања доведе у електронско стање које поседује у комплексном једињењу. Следећи допринос по важности је орбитална стабилизација услед успостављања метал-лиганд хемијске везе. Примарни изазов је представљало успостављање одговарајућег нивоа теорије, објашњење међусобних односа између структурних особина и металног окружења са електронском структуром, као и рационализација добијених резултата и експерименталних података. Научни садржај ове дисертације предлаже рачунарске кораке којима чине DFT поузданом у објашњавању, тумачењу и предвђању карактеристика и својства комплекса прве серије прелазних метала. Рационалном применом предложених методологија, имамо прилику да разјаснимо експерименталне недоумице и искористимо основна начела како бисмо разумели хемијске сложености

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

Nanoparticles have become a vital part of a vast number of established processes and products;they are used as catalysts, in cosmetics, and even by the pharmaceutical industry. Despite this, however, the reliable and reproducible production of functional nanoparticles for specific applications remains a great challenge. In this respect, reticular chemistry provides methods for connecting molecular building blocks to nanoparticles whose chemical composition, structure, porosity, and functionality can be controlled and tuned with atomic precision. Thus, reticular chemistry allows for the translation of the green chemistry principle of atom economy to functional nanomaterials, giving rise to the multifunctional efficiency concept. This principle encourages the design of highly active nanomaterials by maximizing the number of integrated functional units while minimizing the number of inactive components. State-of-the-art research on reticular nanoparticles-metal-organic frameworks, zeolitic imidazolate frameworks, and covalent organic frameworks-is critically assessed and the beneficial features and particular challenges that set reticular chemistry apart from other nanoparticle material classes are highlighted. Reviewing the power of reticular chemistry, it is suggested that the unique possibility to efficiently and straightforwardly synthesize multifunctional nanoparticles should guide the synthesis of customized nanoparticles in the future

Non-covalent interactions in organotin(IV) derivatives of 5,7-ditertbutyl- and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine as recognition motifs in crystalline self- assembly and their in vitro antistaphylococcal activity

Non-covalent interactions are known to play a key role in biological compounds due to their stabilization of the tertiary and quaternary structure of proteins [1]. Ligands similar to purine rings, such as triazolo pyrimidine ones, are very versatile in their interactions with metals and can act as model systems for natural bio-inorganic compounds [2]. A considerable series (twelve novel compounds are reported) of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) were synthesized and investigated by FT-IR and 119Sn M\uf6ssbauer in the solid state and by 1H and 13C NMR spectroscopy, in solution [3]. The X-ray crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 were described, in this latter pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the -OH group of the ethanol moieties. The network of hydrogen bonding and aromatic interactions involving pyrimidine and phenyl rings in both complexes drives their self-assembly. Noncovalent interactions involving aromatic rings are key processes in both chemical and biological recognition, contributing to overall complex stability and forming recognition motifs. It is noteworthy that in Ph2SnCl2(EtOH)2(dptp)2 \u3c0\u2013\u3c0 stacking interactions between pairs of antiparallel triazolopyrimidine rings mimick basepair interactions physiologically occurring in DNA (Fig.1). M\uf6ssbauer spectra suggest for Et2SnCl2(dbtp)2 a distorted octahedral structure, with C-Sn-C bond angles lower than 180\ub0. The estimated angle for Et2SnCl2(dbtp)2 is virtually identical to that determined by X-ray diffraction. Ph2SnCl2(EtOH)2(dptp)2 is characterized by an essentially linear C-Sn-C fragment according to the X-ray all-trans structure. The compounds were screened for their in vitro antibacterial activity on a group of reference staphylococcal strains susceptible or resistant to methicillin and against two reference Gramnegative pathogens [4] . We tested the biological activity of all the specimen against a group of staphylococcal reference strains (S. aureus ATCC 25923, S. aureus ATCC 29213, methicillin resistant S. aureus 43866 and S. epidermidis RP62A) along with Gram-negative pathogens (P. aeruginosa ATCC9027 and E. coli ATCC25922). Ph2SnCl2(EtOH)2(dptp)2 showed good antibacterial activity with a MIC value of 5 \u3bcg mL-1 against S. aureus ATCC29213 and also resulted active against methicillin resistant S. epidermidis RP62A

Classe de Ciências

info:eu-repo/semantics/publishedVersio

First-principles design of hybrid carbon nitride (C2N) with gallium sulphide and gallium selenide two-dimensional (2D) materials as high-performance photovoltaic cells

Abstract: Please refer to full text to view abstract.M.Sc. (Chemistry