How Does the Axial Ligand of Cytochrome P450 Biomimetics Influence the Regioselectivity of Aliphatic versus Aromatic Hydroxylation?

de Visser, Sam P.,Tahsini, Laleh,Nam, Wonwoo WILEY-VCH Verlag 2009 Chemistry Vol.15 No.22

<P>How deep is your orbital? Density functional theory studies on the axial ligand effect of aliphatic versus aromatic hydroxylation of ethylbenzene by iron–oxo complexes with a variable axial ligand show that strong (anionic) ligands pull the metal inside the plane of the haeme and destabilise cationic intermediates through orbital interactions (see picture). <img src='wiley_img/09476539-2009-15-22-CHEM200802234-content.gif' alt='wiley_img/09476539-2009-15-22-CHEM200802234-content'> </P><P>The catalytic activity of high-valent iron–oxo active species of heme enzymes is known to be dependent on the nature of the axial ligand trans to the iron–oxo group. In a similar fashion, experimental studies on iron–oxo porphyrin biomimetic systems have shown a significant axial ligand effect on ethylbenzene hydroxylation, with an axial acetonitrile ligand leading to phenyl hydroxylation products and an axial chloride anion giving predominantly benzyl hydroxylation products. To elucidate the fundamental factors that distinguish this regioselectivity reversal in iron–oxo porphyrin catalysis, we have performed a series of density functional theory calculations on the hydroxylation of ethylbenzene by [Fe<SUP>IV</SUP>&n.dbond;O(Por<SUP>+.</SUP>)L] (Por=porphyrin; L=NCCH<SUB>3</SUB> or Cl<SUP>−</SUP>), which affords 1-phenylethanol and p-ethylphenol products. The calculations confirm the experimentally determined product distributions. Furthermore, a detailed analysis of the electronic differences between the two oxidants shows that their reversed regioselectivity is a result of differences in orbital interactions between the axial ligand and iron–oxo porphyrin system. In particular, three high-lying orbitals (π*<SUB>xz</SUB>, π*<SUB>yz</SUB> and a<SUB>2u</SUB>), which are singly occupied in the reactant complex, are stabilised with an anionic ligand such as Cl<SUP>−</SUP>, which leads to enhanced HOMO–LUMO energy gaps. As a consequence, reactions leading to cationic intermediates through the two-electron reduction of the metal centre are disfavoured. The aliphatic hydroxylation mechanism, in contrast, is a radical process in which only one electron is transferred in the rate-determining transition state, which means that the effect of the axial ligand on this mechanism is much smaller.</P> <B>Graphic Abstract</B> <P>How deep is your orbital? Density functional theory studies on the axial ligand effect of aliphatic versus aromatic hydroxylation of ethylbenzene by iron–oxo complexes with a variable axial ligand show that strong (anionic) ligands pull the metal inside the plane of the haeme and destabilise cationic intermediates through orbital interactions (see picture). <img src='wiley_img/09476539-2009-15-22-CHEM200802234-content.gif' alt='wiley_img/09476539-2009-15-22-CHEM200802234-content'> </P>

The Effect and Influence of <i>cis</i>-Ligands on the Electronic and Oxidizing Properties of Nonheme Oxoiron Biomimetics. A Density Functional Study^†

de Visser, Sam P.,Nam, Wonwoo American Chemical Society 2008 The Journal of physical chemistry A Vol.112 No.50

<P>Density functional theory studies on the nature of the cis effect and cis influence of ligands on oxoiron nonheme complexes have been performed. A detailed analysis of the electronic and oxidizing properties of [Fe<SUP>IV</SUP>═O(TPA)L]<SUP>+</SUP> with L = F<SUP>−</SUP>, Cl<SUP>−</SUP>, and Br<SUP>−</SUP> and TPA = tris-(2-pyridylmethyl)amine are presented and compared with [Fe<SUP>IV</SUP>═O(TPA)NCCH<SUB>3</SUB>]<SUP>2+</SUP>. The calculations show that the electronic cis effect is determined by favorable orbital overlap between first-row elements with the metal, which are missing between the metal and second- and third-row elements. As a consequence, the metal 3d block is split into a one-below-two set of orbitals with L = Cl<SUP>−</SUP> and Br<SUP>−</SUP>, and the HOMO/LUMO energy gap is widened with respect to the system with L = F<SUP>−</SUP>. However, this larger HOMO/LUMO gap does not lead to large differences in electron affinities of the complexes. Moreover, a quantum mechanical analysis of the binding of the ligand shows that it is built up from a large electric field effect of the ligand on the oxoiron species and a much smaller quantum mechanical effect due to orbital overlap. These contributions are of similar strength for the three tested halogen cis ligands and result in similar reactivity patterns with substrates. The calculations show that [Fe<SUP>IV</SUP>═O(TPA)L]<SUP>+</SUP> with L = F<SUP>−</SUP>, Cl<SUP>−</SUP>, and Br<SUP>−</SUP> have closely lying triplet and quintet spin states, but only the quintet spin state is reactive with substrates. Therefore, the efficiency of the oxidant will be determined by the triplet−quintet spin state crossing of the reaction. The reaction of styrene with a doubly charged reactant, that is, [Fe<SUP>V</SUP>═O(TPA)L]<SUP>2+</SUP> with L = F<SUP>−</SUP>, Cl<SUP>−</SUP>, and Br<SUP>−</SUP> or [Fe<SUP>V</SUP>═O(TPA)NCCH<SUB>3</SUB>]<SUP>3+</SUP>, leads to an initial electron transfer from the substrate to the metal followed by a highly exothermic epoxidation mechanism. These reactivity differences are mainly determined by the overall charge of the system rather than the nature of the cis ligand.</P>

The Axial Ligand Effect on Aliphatic and Aromatic Hydroxylation by Non-heme Iron(IV)-oxo Biomimetic Complexes.

de Visser, Sam P,Latifi, Reza,Tahsini, Laleh,Nam, Wonwoo Wiley-VCH 2011 Chemistry - An Asian Journal Vol.6 No.2

<P>Iron(IV)-oxo heme cation radicals are active species in enzymes and biomimetic model complexes. They are potent oxidants in oxygen atom transfer reactions, but the reactivity is strongly dependent on the ligand system of the iron(IV)-oxo group and in particular the nature of the ligand trans to the oxo group (the axial ligand). To find out what effect the axial ligand has on the reactivity of non-heme iron(IV)-oxo species, we have performed a series of density functional theory (DFT) calculations on aliphatic and aromatic hydroxylation reactions by using [Fe(IV) 전(TMC)(L)](n+) (TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, and L=acetonitrile or chloride). The studies show that the regioselectivity of aliphatic over aromatic hydroxylation is preferred. The studies are in good agreement with experimental product distributions. Moreover, the system with the acetonitrile axial ligand is orders of magnitude more reactive than that with a chloride axial ligand. We have analyzed our results and we have shown that the metal-ligand interactions influence the orbital energies and as a consequence also the electron affinities and hydrogen atom abstraction abilities. Thermodynamic cycles explain the regioselectivity preferences.</P>

A Biomimetic Ferric Hydroperoxo Porphyrin Intermediate

de Visser, Sam P.,Valentine, Joan Selverstone,Nam, Wonwoo WILEY-VCH Verlag 2010 Angewandte Chemie Vol.49 No.12

<B>Graphic Abstract</B> <P>OOH, my! The protonation of a side-on high-spin ferric peroxo species yields the corresponding end-on low-spin ferric hydroperoxo intermediate (see picture), which is a precursor of Compound I and has been frequently proposed as a reactive species in heme enzymes. This ferric hydroperoxo complex can be used to study reactivities of similar species in substrate oxygenation and hydroperoxide O&n.bond;O bond cleavage reactions. <img src='wiley_img_2010/14337851-2010-49-12-ANIE200906736-content.gif' alt='wiley_img_2010/14337851-2010-49-12-ANIE200906736-content'> </P>

Intrinsic properties and reactivities of mononuclear nonheme iron-oxygen complexes bearing the tetramethylcyclam ligand

de Visser, S.P.,Rohde, J.U.,Lee, Y.M.,Cho, J.,Nam, W. Elsevier Publishing Company 2013 Coordination chemistry reviews Vol.257 No.2

Iron-oxygen species, such as iron(IV)-oxo, iron(III)-superoxo, iron(III)-peroxo, and iron(III)-hydroperoxo complexes, are key intermediates often detected in the catalytic cycles of dioxygen activation by heme and nonheme iron enzymes. Our understanding of the chemistry of these key intermediates has improved greatly by studies of the structural and spectroscopic properties and reactivities of their synthetic analogues. One class of biomimetic coordination complexes that has proven to be particularly versatile in studying dioxygen activation by metal complexes is comprised of Fe<SUP>IV</SUP>?O and Fe<SUP>III</SUP>?O<SUB>2</SUB>(H) complexes of the macrocyclic tetramethylcyclam ligand (TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). Several recent advances have been made in the synthesis and isolation of new iron-oxygen complexes of this ligand, their structural and spectroscopic characterization, and elucidation of their reactivities in various oxidation reactions. In this review, we summarize the chemistry of the first structurally characterized mononuclear nonheme iron(IV)-oxo complex, in which the Fe<SUP>IV</SUP>?O group was stabilized by the TMC ligand. Complexes with different axial ligands, [Fe<SUP>IV</SUP>(O)(TMC)(X)]<SUP>n+</SUP>, and complexes of other cyclam ligands are discussed as well. Very recently, significant progress has also been reported in the area of other iron-oxygen intermediates, such as iron(III)-superoxo, iron(III)-peroxo, and iron(III)-hydroperoxo complexes bearing the TMC ligand. The present results demonstrate how synthetic and mechanistic developments in biomimetic research can advance our understanding of dioxygen activation occurring in mononuclear nonheme iron enzymes.

Mean value first principle engine model for predicting dynamic behaviour of two-stroke marine diesel engine in various ship propulsion operations

Sui Congbiao,de Vos Peter,Stapersma Douwe,Visser Klaas,Hopman Hans,Ding Yu 대한조선학회 2022 International Journal of Naval Architecture and Oc Vol.14 No.1

Analysis of ship propulsion system performance is often performed using detailed hydrodynamic models to assess load changes, which are subsequently compared to static engine limits, or by detailed engine models that are rarely integrated with sufficiently detailed propulsion models for load change estimation. To investigate the dynamic engine (overloading) behaviour and ship propulsion performance under various heavy operating conditions, a Mean Value First Principle Parametric (MVFPP) engine model is integrated into a ship propulsion system model in this paper. An upgraded thermodynamic-based MVFPP model for two-stroke marine diesel engines is presented, in particular a newly developed MVFPP gas exchange model. Based on the integrated propulsion system model of a benchmark ocean-going chemical tanker, the engine dynamic behaviour during ship acceleration, deceleration and crash stop has been investigated. Results show that, during dynamic processes, the engine could be thermally overloaded even if the engine power trajectory is inside the static engine operating envelope. The paper contributes to finding proper indicators for thermal overloading of modern two-stroke marine diesel engines. It is demonstrated that when matching the engine with the propeller and designing the ship propulsion control system, not only the static engine operating envelope, but also the dynamic engine behaviour should be considered.

Effect of Porphyrin Ligands on the Regioselective Dehydrogenation versus Epoxidation of Olefins by Oxoiron(IV) Mimics of Cytochrome P450^†

Kumar, Devesh,Tahsini, Laleh,de Visser, Sam P.,Kang, Hye Yeon,Kim, Soo Jeong,Nam, Wonwoo American Chemical Society 2009 The Journal of physical chemistry A Vol.113 No.43

<P>The cytochromes P450 are versatile enzymes involved in various catalytic oxidation reactions, such as hydroxylation, epoxidation and dehydrogenation. In this work, we present combined experimental and theoretical studies on the change of regioselectivity in cyclohexadiene oxidation (i.e., epoxidation vs dehydrogenation) by oxoiron(IV) porphyrin complexes bearing different porphyrin ligands. Our experimental results show that meso-substitution of the porphyrin ring with electron-withdrawing substituents leads to a regioselectivity switch from dehydrogenation to epoxidation, affording the formation of epoxide as a major product. In contrast, electron-rich iron porphyrins are shown to produce benzene resulting from the dehydrogenation of cyclohexadiene. Density functional theory (DFT) calculations on the regioselectivity switch of epoxidation vs dehydrogenation have been performed using three oxoiron(IV) porphyrin oxidants with hydrogen atoms, phenyl groups, and pentachlorophenyl (ArCl<SUB>5</SUB>) groups on the meso-position. The DFT studies show that the epoxidation reaction by the latter catalyst is stabilized because of favorable interactions of the substrate with halogen atoms of the meso-ligand as well as with pyrrole nitrogen atoms of the porphyrin macrocycle. Hydrogen abstraction transition states, in contrast, have a substrate-binding orientation further away from the porphyrin pyrrole nitrogens, and they are much less stabilized. Finally, the regioselectivity of dehydrogenation versus hydroxylation is rationalized using thermodynamic cycles.</P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp9028694'>ACS Electronic Supporting Info</A></P>

Further results on the development of a novel VTOL aircraft, the Anuloid. Part II: Flight mechanics

Petrolo, Marco,Carrera, Erasmo,Visser, Coen de,D'Ottavio, Michele,Polit, Olivier Techno-Press 2017 Advances in aircraft and spacecraft science Vol.4 No.4

This paper presents the main outcomes of the preliminary development of the Anuloid, an innovative disk-shaped VTOL aircraft. The Anuloid has three main features: lift is provided by a ducted fan powered by a turboshaft; control capabilities and anti-torque are due to a system of fixed and movable surfaces that are placed in the circular internal duct and the bottom portion of the aircraft; the Coanda effect is exploited to enable the control capabilities of such surfaces. In this paper, results from flight mechanics are presented. The vertical flight dynamics were found to be desirable. In contrast, the horizontal flight dynamics of the aircraft shows both dynamic instability, and more importantly, insufficient pitch and roll control authority. Some recommendations and guidelines are then given aimed at the alleviation of such problems.

On the development of the Anuloid, a disk-shaped VTOL aircraft for urban areas

Petrolo, Marco,Carrera, Erasmo,D'Ottavio, Michele,de Visser, Coen,Patek, Zdenek,Janda, Zdenek Techno-Press 2014 Advances in aircraft and spacecraft science Vol.1 No.3

This paper deals with the early development of the Anuloid, an innovative disk-shaped VTOL aircraft. The Anuloid concept is based on the following three main features: the use of a ducted fan powered by a turboshaft for the lift production to take-off and fly; the Coanda effect that is developed through the circular internal duct and the bottom portion of the aircraft to provide further lift and control capabilities; the adoption of a system of ducted fixed and swiveling radial and circumferential vanes for the anti-torque mechanism and the flight control. The early studies have been focused on the CFD analysis of the Coanda effect and of the control vanes; the flyability analysis of the aircraft in terms of static performances and static and dynamic stability; the preliminary structural design of the aircraft. The results show that the Coanda effect is stable in most of the flight phases, vertical flight has satisfactory flyability qualities, whereas horizontal flight shows dynamic instability, requiring the development of an automatic control system.

Regioselectivity of aliphatic <i>versus</i> aromatic hydroxylation by a nonheme iron(<small>II</small>)-superoxo complex

Latifi, Reza,Tahsini, Laleh,Nam, Wonwoo,de Visser, Sam P. The Royal Society of Chemistry 2012 Physical chemistry chemical physics Vol.14 No.7

<P>Many enzymes in nature utilize molecular oxygen on an iron center for the catalysis of substrate hydroxylation. In recent years, great progress has been made in understanding the function and properties of iron(<SMALL>IV</SMALL>)-oxo complexes; however, little is known about the reactivity of iron(<SMALL>II</SMALL>)-superoxo intermediates in substrate activation. It has been proposed recently that iron(<SMALL>II</SMALL>)-superoxo intermediates take part as hydrogen abstraction species in the catalytic cycles of nonheme iron enzymes. To gain insight into oxygen atom transfer reactions by the nonheme iron(<SMALL>II</SMALL>)-superoxo species, we performed a density functional theory study on the aliphatic and aromatic hydroxylation reactions using a biomimetic model complex. The calculations show that nonheme iron(<SMALL>II</SMALL>)-superoxo complexes can be considered as effective oxidants in hydrogen atom abstraction reactions, for which we find a low barrier of 14.7 kcal mol<SUP>−1</SUP> on the sextet spin state surface. On the other hand, electrophilic reactions, such as aromatic hydroxylation, encounter much higher (>20 kcal mol<SUP>−1</SUP>) barrier heights and therefore are unlikely to proceed. A thermodynamic analysis puts our barrier heights into a larger context of previous studies using nonheme iron(<SMALL>IV</SMALL>)-oxo oxidants and predicts the activity of enzymatic iron(<SMALL>II</SMALL>)-superoxo intermediates.</P> <P>Graphic Abstract</P><P>Calculations show that iron(<SMALL>II</SMALL>)-superoxo is a possible oxidant in hydrogen abstraction reactions but not in aromatic hydroxylation reactions. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2cp23352e'> </P>