Axial and Equatorial Ligand Effects of Bioinspired Tetracarbene Iron Models for Heme and Non-Heme Enzymes
by Isabelle Becker
Date of Examination:2025-04-24
Date of issue:2025-06-12
Advisor:Prof. Dr. Franc Meyer
Referee:Prof. Dr. Franc Meyer
Referee:Prof. Dr. Inke Siewert
Persistent Address:
http://dx.doi.org/10.53846/goediss-11291
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Abstract
English
The selective oxidation of hydrocarbons with sustainable oxidants is still a challenging reaction in industry. In order to create a sustainable future—especially in regard of progressing climate change—finding alternative oxidation processes is of high interest. In this regard, inspiration from nature can help. For example, natural enzymes can perform the hydroxylation of earth-abundant hydrocarbons at ambient conditions and with high rates. Inspired by enzymes containing iron in the active center, chemists have developed model complexes to understand how the intermediates of such enzymes can perform those challenging reactions. In this work, model complexes in multiple oxidation states with different equatorial tetracarbene macrocycles as well as various axial ligations were synthesized and fully characterized, analyzing their electronic structure and reactivity. Building on previous results on organometallic tetracarbene iron(II) complexes 1, missing spectroscopical data were added in this work and a detailed study of the equatorial ligand perturbation was carried out. In this regard, the influence of peripheral substitution of H-atoms by methyl groups as well as the modification of the ring size (18-membered vs. 16-membered macrocycles) was investigated. In addition, series of low-spin tetracarbene iron(III) complexes 2 and intermediate-spin tetracarbene iron(III) complexes 3 were synthesized and spectroscopically analyzed, in which the spin-state change could be induced by variation of solvent. Due to the relevance of thiolato complexes in nature, for example the coordination of the cysteinato ligand to multiple high-valent active centers in enzymes, the effect of thiolato coordination on the iron(II) platform was studied in greater detail. Therefore, the 18-membered complexes 1 were reacted with different thiolate salts to obtain iron(II) complexes with different trans-axial thiolato ligands, as well as different equatorial ligations. Hereby, a series of thiolatoiron(II) complexes 4 and 5 was obtained, showing variations in spin-state and coordination geometry, emphasizing the flexibility of the tetracarbene platform. The electronic structure and geometry of those complexes was studied in detail in solid-state as well as in solution by (field-dependent) Mössbauer spectroscopy, SQUID measurements, NMR, IR and UV-Vis spectroscopic studies as well as with cyclic voltammetry. In addition, two series of oxidoiron(IV) complexes based on the 18-membered equatorial macrocycles with different axial ligands (MeCN coordination (6), trifluoroacetato (7) and thiolato ligation (8 and 9)) were investigated. Previous spectroscopic studies on 6-18H, 7-18H and 8-18H were expanded in this work and complexes 9-18H, 6-18Me, 7-18Me and 8-18Me were newly synthesized. The substituted tetracarbene oxidoiron(IV) complexes were further characterized using UV/Vis, (field-dependent) Mössbauer, IRPD spectroscopy, SQUID magnetometry and crystallography (in the case of 9), confirming their electronic structure with a S = 1 spin ground state and a high triplet-quintet energy separation. IRPD spectroscopy showed a decrease of the Fe=O stretching frequency going from 6 to 8/9, supporting the increasing axial donation. Similar findings were obtained for the peripheral methylated as well as non-methylated complexes, so that the peripheral substitution is expected to only slightly influence the electronic configuration of the oxidoiron(IV) unit. Due to the large triplet-quintet energy separation, influences from two-state reactivity can be neglected for the tetracarbene system and therefore, the axial and equatorial ligand effects on hydrogen atom abstraction (HAA) were disentangled by using substrates with weak C−H bonds (1,4- cyclohexadiene (CHD), 9,10-dihydroanthracene (DHA)/ deuterated DHA, 9H-xanthene and 10-methyl-9,10-dihydroacridine (AcrH2)). UV/Vis monitoring of the reaction in pseudo-first order conditions at different temperatures yielded kinetic traces, from whose Eyring activation parameters and Bell-Evans-Polanyi type correlations were derived. Interestingly, the presence of strong axial donors decreased the reaction rates compared to 6, in line with an electrophilic trend. Temperature-dependent kinetic isotope effect (KIE) studies and calculations underlined a special role of thiolato-coordinated complexes 8 and 9 due to increased tunnelling, therefore showing faster rates than complex 7. Peripheral methylation of the complexes slowed down all rates, again in line with an electrophilic trend for HAA. Additionally, the reactivity of the different bis(acetonitrile)iron(II) complexes 1 towards dioxygen as an abundant natural oxidant was studied. This is of great interest since dioxygen is readily available and natural enzymes are using it as an oxidizing agent during their catalytic cycles forming different high-valent intermediates. Therefore, the replacement of artificial oxidizing agents like sPhIO (2 (tert butylsulfonyl)iodosobenzene) by sustainable ones is one goal in the field of catalysis by high-valent oxidoiron complexes to obtain greener reaction conditions. At room temperature, complexes μ-oxidodiiron(III) complexes 12 were obtained and characterized. Both μ-oxidodiiron(III) complexes 12-16H and 12-16Me were spectroscopically analyzed and showed similar features in UV-Vis, Mössbauer and Raman spectroscopy. Raman spectroscopic analyses of all μ-oxidodiiron(III) complexes of the series 12 suggested an unusual dependence of the stretching bands on the Fe–O–Fe angles. In scrambling experiments using 12-16H and 12-16Me, a mixed complex 12-16H/Me was obtained, likely due a disproportionation equilibrium forming bis(acetonitrile)iron(II) complex 1-16Me and oxidoiron(IV) complex 6-16Me. This equilibrium can explain a range of different reactivities: 12-16Me can undergo two-electron OAT reactions with phospines as well as HAA reactions with DHA due to the involvement of the oxidoiron(IV) complex.
Keywords: Bioinorganic Chemistry; Iron; N-Heterocyclic Carbenes; Heme Enzymes; Non-Heme Enzymes; Hydrogen Atom Abstraction; Electronic Structure; Oxidoiron(IV) Complexes; Axial Ligand Effects; Equatorial Ligand Effects
