Computational Study of the Role of Coordinated Ligand Architecture on the Oxidation Reactions Catalysed by Transition Metal-based Complexes

Abstract

Chapter 1 This chapter offers a concise overview of the broad applications of transition metal complexes, with a focus on reaction catalysis by iron (Fe) complexes. In particular, the chapter delves into oxidation reactions mediated by Fe(IV)O species, both heme and non-heme, emphasizing the rapidly growing field of C-H activation. The literature relevant to this process has been systematically reviewed, depicting how biological enzymes inspired biomimetic complexes to carry out these reactions. Various concepts, such as Two State Reactivity, and mechanisms of the proposed transfers have been deliberated. A detailed discussion on the influence of factors such as ligand architecture, on these activation processes is provided. Ligand architecture, including modifications to both the axial and equatorial coordination environments, plays a pivotal role in governing the reactivity of these complexes. Studies have shown that alterations to these ligands, such as heteroatom substitutions, can significantly impact reaction dynamics, influencing parameters like redox potentials and activation barriers. Furthermore, an assessment of gaps in the current literature is presented, with particular emphasis on recent advancements in the field. These insights are crucial for guiding the rational design of nextgeneration catalysts with improved performance and selectivity. The chapter concludes by outlining the objectives of the current research, aiming to address these identified gaps. Chapter 2 This chapter provides an in-depth introduction to the essential principles and methodologies of computational chemistry. It begins by explaining quantum mechanics (QM) as the theoretical basis for many computational methods, particularly highlighting the Schrodinger equation as the core equation governing quantum systems. While the exact solution of this equation is only feasible for single-electron systems, approximations are necessary for multi-electron systems. The Born-Oppenheimer approximation is then discussed followed by Hartree-Fock (HF) theory, which is introduced as an ab initio method for solving the Schrodinger equation, though its limitations in accounting for electron-electron corelations are addressed. Post-HF methods, developed to include electron correlation, are described as important advancements to improve accuracy, despite their higher computational cost. The chapter further elaborates on Density Functional Theory (DFT), which is based on the electron density rather than wave functions, making it a widely used approach due to its balance between computational efficiency and v accuracy. The chapter explores the use of functionals like B3LYP, which has been proven to show results with great accuracy in this field. Other factors such as basis sets and solvent models employed have been discussed. Additionally, the chapter discusses the advanced computational tools used in modern chemistry, such as Gaussian 16 for geometry optimization, frequency analysis, and thermochemistry. Visualization tools like Chemcraft is highlighted for their ability to provide molecular structures, bond lengths, atomic charges, and spin densities. Other tools, such as KiSThelP software, are described as valuable for studying tunneling effects and kinetic analysis. Overall, the chapter not only outlines the theoretical frameworks but also demonstrates the practical tools and techniques of computational chemistry, setting the stage for the more detailed studies presented in later sections. Chapter 3 A comprehensive DFT investigation has been presented in this chapter to address the role of equatorial sulfur ligation in C-H activation. A nonheme iron-oxo compound with four nitrogen atoms constituting the equatorially connected macrocyclic framework (represented as N4) [Fe(IV)O(THC)(CH3CN)]2+(THC = 1,4,8,11-tetrahydro1,4,8,11-tetraazacyclotetradecane), has been considered as the base compound. Other complexes have been anticipated by the sequential replacement of this nitrogen by sulfur i.e., N4, N3S1, N2S2, N1S3, and S4. Generally, the anti-conformers (with respect to equatorial N-H and Fe=O) turned out to be the most stable. It was found that with the enrichment of the equatorial sulfur atom, reactivity increases successively, i.e., we get the trend N4 < N3S1 < N2S2 < N1S3 < S4. Our investigations have also verified the available experimental results, where it has been reported that N2S2 is more reactive than N4 in their mixed conformation. In search of insight into this typical pattern of reactivity, the interplay of several factors has been recognised, such as the distortion energy - distortion energy decreases for the transition states with the addition of sulfur; the spin density - the spin density on the oxygen atom increases, implying that the radical character of the abstractor increases on sulfur ligation; the energy of the electron acceptor orbital - the energy of the LUMO (σ*z2) decreases continuously with the sulfur substitution; and the triplet-quintet oxidant energy gap—the energy gap decreases consistently with S-enrichment in the equatorial position. The computational predictions reported here, if further validated by experiments, will definitely encourage the synthesis of sulfur-ligated bioinspired complexes instead of the ones constituting nitrogen exclusively. vi Chapter 4 In this chapter, we present a meticulous computational study to foresee the effect of an oxygenrich macrocycle on the reactivity of C-H activation. For this study, a widely studied nonheme Fe(IV)O molecule with a TMC (1,4,8,11-tetramethyl 1,4,8,11-tetraazacyclotetradecane) macrocycle that is equatorially attached to four nitrogen atoms (designated as N4) and acetonitrile as an axial ligand has been taken into account. For the goal of hetero-substitution, the step-by-step replacement of the N4 framework by O atoms, i.e., N4, N3O1, N2O2, N1O3, and O4 systems, has been considered, and dihydroanthracene (DHA) has been used as the substrate. In order to neutralise the system and prevent the self-interaction error in DFT, counterions called triflates have also been included in the calculations. Studying the energetics of these CH bond activation reactions and the potential energy surfaces mapped therefore reveals that the initial hydrogen abstraction, which is the rate-determining step, follows the two-state reactivity (TSR) patterns, which means that the originally excited quintet state falls lower in the transition state and product. The reaction follows the hydrogen atom transfer (HAT) mechanism, as indicated by the spin density studies. The results revealed a fascinating reactivity order, in which the reactivity increases with the enrichment of the oxygen atom in the equatorial position, namely, the order follows N4 < N3O1 < N2O2 < N1O3 < O4. The impact of oxygen substitution on quantum mechanical tunneling and H/D kinetic isotope effect studies have also been investigated. When analysing the causes of this reactivity pattern, a number of variables have been identified, including the reactant like transition structure, spin density distribution, the distortion energy, and the energies of the electron acceptor orbital, i.e., the energy of LUMO (σ*z2), which validate the obtained outcome. Our results also show very good agreement with earlier combined experimental and theoretical studies considering TMC and TMCO-type complexes. The DFT predictions reported here will undoubtedly encourage experimental research in this biomimetic field, as they provide an alternative with higher reactivity in which heteroatoms can be substituted for traditional nitrogen atoms. Chapter 5 In the first part of this chapter, a DFT investigation has been presented to demonstrate the relevance of the macrocyclic ligand ring size of the high-valent non heme Fe(IV)O complexcatalyzed C-H activation process. Tetramethylcyclam (TMC) with varying ring size measures in terms of n = 12, 13, 14, 15, and 16 in [Fe(IV)O(n-TMC)(CH3CN)]2+ has been considered as the oxidant and dihydroanthracene as the general substrate. Computations were also carried out vii to determine the effect of the axial ligand-acetonitrile on the C-H activation reactivity. It was discovered that the complexes without axial ligands turned out to be more reactive compared to their axially coordinated counterpart. The most intriguing finding, however, was that reactivity increased steadily with ring size increments, giving us the trend 12<13<14<15<16. Behind this typical pattern of reactivity, several factors played a role, including the energy of electron acceptor orbital which sequentially decreases, distortion energy to achieve the transition state which also decreases as we move on from n=12 to 16. The triplet-quintet energy difference of the oxidants also has a part to play, as it decreases with increased ring size, with the quintet becoming more and more dominant. The current studies were also able to corroborate the experimental data that was published regarding Fe(IV)O(13-TMC) (without axial syn form) having a higher C-H activation reactivity than Fe(IV)O(14-TMC) (with axial anti-form). On the whole, this computational presentation gives us a reactivity pattern relying on the ring size commutes and can lead to successful experimental results if pursued based on this reaction. The second part consists of the heme complexes, presenting a detailed comparative analysis of C-H activations catalysed by three different Fe(IV)O porphyrinoid complexes. The study considers the usual heme porphyrin (complex I) as the base compound, porphyrazine (complex II), which is obtained by replacing carbon with nitrogen at the meso position, and phthalocyanine (complex III), which is obtained through the peripheral benzoannulation of porphyrazine. The main focus here is to explore the impact of bridging groups and peripheral functionalisation in heme systems on reactivity. Chloride is used as the axial ligand for all complexes, and DHA is used as the substrate. Factors such as distortion energy and different electron acceptor orbitals significantly affect the overall reactivity. The effect of substitution on quantum mechanical tunneling using H/D kinetic isotope effect studies is also included. The results reveal a fascinating reactivity order: mesonitrogen substitution enhances reactivity, while additional benzo-annulation hinders reactivity, leading to the order complex II > complex I > complex III. In comparison to the usual model compound I, which is Fe(IV)O-porphyrin π cation radical with an –SH axial ligand, complex II was found to be more reactive. These findings support the use of accessible iron frameworks derived from porphyrin in C-H activation processes. viii Chapter 6 This chapter provides conclusion drawn from the research work presented in previous chapters by using DFT to investigate the reactivity and mechanisms of Fe(IV)Oxo complexes, focusing on ligand architecture modifications. Key findings include that hetero-substitution, such as replacing nitrogen with sulfur in macrocyclic ligands, significantly enhances C-H activation reactivity. Additionally, changes in the coordination sphere, including ring size and axial ligand removal, further optimise catalytic efficiency. Studies on heme complexes reveal that structural changes, such as nitrogen substitution and benzo-annulation, influence reactivity patterns. Theoretical results align well with experimental data, confirming the reliability of the reactivity trends. The outlook section proposes expanding research to other metal frameworks, such as manganese and metal-oxygen species, and continuing to explore ligand modifications in hemetype complexes for further catalytic optimization.