Selected Aspects of Enzymatic Catalytic Activity Studied by Theoretical Methods and Implementation of the Analytic Second Derivatives of Hartree-Fock and Hybrid Density Functional Energies

This thesis deals with application of modern theoretical methods for studying enzymatic reactivity as well as with the efficient implementation of second analytical energy derivatives on the self-consistent field (SCF) theory level. The enzymatic mechanisms were investigated in the framework of electronic structure theory with special accent put on kinetics, proton-coupled electron transfer and theoretical support of EPR and Mössbauer experiments. In particular, cytochrome c nitrite reductase (CcNiR) enzyme mechanism was under consideration. The possible role of second-sphere active site amino acids as proton donors was investigated by taking different possible protonation states and geometrical conformations into account. It was found that the most probable proton donor is His277, whose spatial orientation and fine-tuned acidity lead to energetically feasible, low-barrier protonation reactions. However, substrate protonation may also be accomplished by Arg114. The activation barriers for the various proton and electron transfer steps were estimated in the framework of Marcus theory. The cd1 nitrite reductase (NIR) enzyme was also investigated. NIR is a key enzyme in the denitrification process that reduces nitrite to nitric oxide (NO). There are three residues at the “distal” side of the active site heme (Tyr10, His327 and His369) and in this work the focus was set on the identification and characterization of possible H-bonds they can form with the NO, thereby affecting the stability of the complex. It was shown that the NO in the nitrosyl d1-heme complex of cd1 NIR forms H-bonds with Tyr10 and His369 whereas the second conserved histidine, His327, appears to be less involved in NO H-bonding. Moreover, it was shown that the H-bonding network within the active site is dynamic and that a change in the protonation state of one of the residues does affect the strength and position of the H-bonds formed by the others. The electronic structure of the [4Fe-3S] cluster in Hydrogenase I (Hase I) was considered. The cluster performs two redox transitions within a very small potential range, forming a super-oxidized state above +200 mV vs SHE. The field-dependent 57Fe-Mössbauer and EPR data for Hase I is presented, which in conjunction with spectroscopically calibrated DFT calculations, reveal the distribution of Fe valences and spin-coupling schemes for the iron-sulfur clusters. The theory part of the thesis includes conventional implementation of SCF second derivatives into ORCA set of programs combined with efficient approximations. The second derivatives of electronic energy are the base for the calculation of force constants, harmonic vibration frequencies, infra red (IR) and Raman intensities. To speed up the evaluation of the hessian, in particular the two-electron integrals and their derivatives, the resolution of the identity (RI) and the Chain of Spheres (COS) approximations can be applied. As part of the present work, the RI and COS approximations are introduced at various stages of the molecular Hessian evaluation procedure, e.g., the reference energy calculation, various steps of the coupled-perturbed SCF procedure, and the final integral derivative evaluation. The performance of the approximations and possible errors introduced are discussed in details. The applicability of the Hessian program was also greatly extended by the additional functionality such as effective core potentials (ECP), Van der Waals corrected second derivatives and QM/MM hessian

Imaging of early stage breast cancer with circularly polarized light

In this study, we utilize the properties of polarized light for the analysis of paraffin-embedded breast cancer samples. We perform the measurements of the full Stokes vector of back-reflected radiation and calculate the degree of polarization as a diagnostic criterion for the separation of healthy and cancer sample sections. We show that circularly polarized light scattered within the breast sample is sensitive to the presence of cancer cells. The degree of the polarization of the reected light was found to be the most sensitive parameter for the reliable differentiation of tissue

Coupled cluster theory on modern heterogeneous supercomputers

This study examines the computational challenges in elucidating intricate chemical systems, particularly through ab-initio methodologies. This work highlights the Divide-Expand-Consolidate (DEC) approach for coupled cluster (CC) theory—a linear-scaling, massively parallel framework—as a viable solution. Detailed scrutiny of the DEC framework reveals its extensive applicability for large chemical systems, yet it also acknowledges inherent limitations. To mitigate these constraints, the cluster perturbation theory is presented as an effective remedy. Attention is then directed towards the CPS (D-3) model, explicitly derived from a CC singles parent and a doubles auxiliary excitation space, for computing excitation energies. The reviewed new algorithms for the CPS (D-3) method efficiently capitalize on multiple nodes and graphical processing units, expediting heavy tensor contractions. As a result, CPS (D-3) emerges as a scalable, rapid, and precise solution for computing molecular properties in large molecular systems, marking it an efficient contender to conventional CC models

Взаємозв’язок бюджетного дефіциту з інфляцією та ВВП

Розробка проблематики взаємозв’язку бюджетного дефіциту з ВВП та інфляцією має науково-практичне значення. Воно полягає в тому, що ефективно управляючи дефіцитом бюджету як інструментом державної фінансової політики, можна здійснювати позитивний економічний вплив на ВВП та інфляцію.Development of the relationship problems of budget deficit to GDP and inflation has scientific and practical importance. Effectively managing the budget deficit as an instrument of state fiscal policy makes it possible to exercise the positive economic impact on GDP and inflation.Разработка проблематики взаимосвязи бюджетного дефицита с ВВП и инфляцией имеет научно-практическое значение. Оно заключается в том, что эффективно управляя дефицитом бюджета, как инструментом государственной финансовой политики, можно осуществлять позитивное экономическое влияние на ВВП и инфляцию

СУЧАСНІ МЕТОДИ ПРОЕКТУВАННЯ КАР'ЄРІВ

The analysis of existing quarries design techniques. The modern design methods using packages Gemcom for Windows applications and SurfCADDПредставлен анализ существующих методов проектирования карьеров. Рассмотрены современные методы проектирования с помощью пакетов прикладных программ Gemcom  for Windows и SurfCADDПредставлений аналіз існуючих методів проектування кар'єрів. Розглянуто сучасні методи проектування за допомогою пакетів прикладних програм Gemcom for Windows і SurfCAD

УМОВИ ВИНИКНЕННЯ ВІДМОВ СВЕРДЛОВИННИХ ЗАРЯДІВ ПРИ МАСОВИХ ВИБУХАХ

The conditions of failures downhole explosive charges with short-delay firing. Installed interval of distances between the charges, in which possible failure of the detonation charge, initiated by the slowdownРассмотрены условия возникновения отказов скважинных зарядов взрывчатых веществ при короткозамедленном взрывании. Установлен интервал расстояний между зарядами, в котором возможен срыв детонациизаряда, инициируемого с замедлениемРозглянуто умови виникнення відмов свердловинних зарядів вибухових речовин при уповільненого відривання. Встановлено інтервал відстаней між зарядами, в якому можливий зрив детонації заряду, ініційованого з уповільнення

АНАЛІЗ ПРИЧИН ВІДМОВ СВЕРДЛОВИННИХ ЗАРЯДІВ НА КАР’ЄРІ ВАТ "ПОЛТАВСЬКИЙ ГЗК"

The reasons for the failure of borehole charges in quarries are considered. The main causes of failures at enterprises leading explosive work with the application of a detonating cord. Recommended activities to reduce the number of failures. A detailed analysis of failures well charges on the open pit of the DNU of JSC "Poltava GOK"Рассмотрены причины отказов скважинных зарядов на карьерах.Приведены основные причины отказов на предприятиях, ведущих взрывныеработы с применением детонирующего шнура. Рекомендованы мероприятияпо снижению количества отказов. Проведен детальный анализ отказовскважинных зарядовна карьере ДнРУ ОАО "Полтавский ГОК"Розглянуто причини відмов свердловинних зарядів на кар'єрах. Наведено основні причини відмов на підприємствах, що ведуть вибухові роботи із застосуванням детонуючого шнура. Рекомендовані заходи щодо зниження кількості відмов. Проведено детальний аналіз відмов свердловинних зарядовна кар'єрі ДнРУ ВАТ "Полтавський ГЗК

Indefinitely stable iron(IV) cage complexes formed in water by air oxidation

In nature, iron, the fourth most abundant element of the Earth’s crust, occurs in its stable forms either as the native metal or in its compounds in the +2 or +3 (low-valent) oxidation states. High-valent iron (+4, +5, +6) compounds are not formed spontaneously at ambient conditions, and the ones obtained synthetically appear to be unstable in polar organic solvents, especially aqueous solutions, and this is what limits their studies and use. Here we describe unprecedented iron(IV) hexahydrazide clathrochelate complexes that are assembled in alkaline aqueous media from iron(III) salts, oxalodihydrazide and formaldehyde in the course of a metal-templated reaction accompanied by air oxidation. The complexes can exist indefinitely at ambient conditions without any sign of decomposition in water, nonaqueous solutions and in the solid state. We anticipate that our findings may open a way to aqueous solution and polynuclear high-valent iron chemistry that remains underexplored and presents an important challenge