Axial and equatorial ligand effects on biomimetic cysteine dioxygenase model complexes

Density functional theory (DFT) calculations are presented on biomimetic model complexes of cysteine dioxygenase and focus on the effect of axial and equatorial ligand placement. Recent studies by one of us [Y. M. Badiei, M. A. Siegler and D. P. Goldberg, J. Am. Chem. Soc. 2011, 133, 1274] gave evidence of a nonheme iron biomimetic model of cysteine dioxygenase using an i-propyl-bis(imino)pyridine, equatorial tridentate ligand. Addition of thiophenol, an anion - either chloride or triflate - and molecular oxygen, led to several possible stereoisomers of this cysteine dioxygenase biomimetic complex. Moreover, large differences in reactivity using chloride as compared to triflate as the binding anion were observed. Here we present a series of DFT calculations on the origin of these reactivity differences and show that it is caused by the preference of coordination site of anion versus thiophenol binding to the chemical system. Thus, stereochemical interactions of triflate and the bulky iso-propyl substituents of the ligand prevent binding of thiophenol in the trans position using triflate. By contrast, smaller anions, such as chloride, can bind in either cis or trans ligand positions and give isomers with similar stability. Our calculations help to explain the observance of thiophenol dioxygenation by this biomimetic system and gives details of the reactivity differences of ligated chloride versus triflate.     

Boron–Ligand Cooperation: The Concept and Applications

The term boron–ligand cooperation was introduced to describe a specific mode of action by which certain metal-free systems activate chemical bonds. The main characteristic of this mode of action is that one covalently bound substituent at the boron is actively involved in the bond activation process and changes to a datively bound ligand in the course of the bond activation. Within this review, how the term boron–ligand cooperation evolved is reflected on and examples of bond activation by boron–ligand cooperation are discussed. It is furthermore shown that systems that operate via boron–ligand cooperation can complement the reactivity of classic intramolecular frustrated Lewis pairs and applications of this new concept for metal-free catalysis are summarized.     

How to integrate biological motors towards bio-actuators fueled by ATP

Biological motors, driven by the conversion of chemical energy into mechanical energy, are much more efficient than man-made machines. The development of such efficient biomimetic motor systems in vitro is currently a vital need. However, great difficulty lies in how to integrate the sophisticated functions of the constituent components to obtain a performance as in the case of natural living systems. Based on 'active' and 'passive' self-organization principles, it has been demonstrated that the functions of motor protein systems can be integrated to obtain complex hierarchical structures that can work as actuators. Most of the works discussed here concern two-dimensional behavior, and recent works aim to explore the three-dimensional features of such artificial bio-mechanical systems.     

Chemical activity of the nitrogenase FeMo cofactor with a central nitrogen ligand: density functional study

We investigate the chemical consequences of a central ligand in the nitrogenase FeMo cofactor using density functional calculations. Several studies have shown that the central ligand most probably is a nitrogen atom, but the consequences for the chemical reactivity of the cofactor are unknown. We investigate several possible routes for insertion of the central nitrogen ligand and conclude that all routes involve barriers and intermediate states, which are inaccessible at ambient conditions. On this basis we suggest that the central nitrogen ligand is present at all times during the reaction. Furthermore, we investigate how the FeMoco with the central ligand can interact with N(2) and reduce it.     

Oxo complexes of high-valence iron in oxidation catalysis

This review deals with oxo complexes of high-valence iron (oxoferryl, or simply ferryl complexes), which play an important role in the selective oxidation of hydrocarbons and other organic compounds. The efficiency and high selectivity of natural oxygenases stimulates researchers to design chemical analogues of these systems. Since the advantages of biological and biomimetic oxidation are due to the participation of ferryl intermediates, we will consider the ways of obtaining relatively stable oxo complexes of high-valence iron and their geometric and electronic structure and reactivity.     

仿生干湿摩擦黏附器件的研究进展

生物在自然界的演化过程中进化出了许多独特的干湿摩擦、黏附器官来适应其生存环境.研究人员通过对自然界中典型摩擦与黏附现象的研究、认识和总结,提出了相应的仿生界面摩擦、黏附理论与模型,用于指导人工合成型智能摩擦黏附材料与器件.目前,仿生摩擦、黏附材料体系与器件的设计策略主要以表面微结构、界面物理化学相互作用以及机械形变为基...     

The Equatorial Ligand Effect on the Properties and Reactivity of Iron(V) Oxo Intermediates

High-valent metal oxo oxidants are common catalytic-cycle intermediates in enzymes and known to be highly reactive. To understand which features of these oxidants affect their reactivity, a series of biomimetic iron(V) oxo oxidants with peripherally substituted biuret-modified tetraamido macrocyclic ligands were synthesized and characterized. Major shifts in the UV/Vis absorption as a result of replacing a group in the equatorial plane of the iron(V) oxo species were found. Further characterization by EPR spectroscopy, ESI-MS, and resonance Raman spectroscopy revealed differences in structure and the electronic configuration of these complexes. A systematic reactivity study with a range of substrates was performed and showed that the reactions are affected by electron-withdrawing substituents in the equatorial ligand, which enhance the reaction rate by almost 10¹⁶ orders of magnitude. Thus, the long-range electrostatic perturbations have a major influence on the rate constant. Finally, computational studies identified the various electronic contributions to the rate-determining reaction step and explained how the equatorial ligand periphery affects the properties of the oxidant.     

Oxidative double dehalogenation of tetrachlorocatechol by a bio-inspired CuII complex: formation of chloranilic acid

Copper(II) complexes of the potentially tripodal N,N,O ligand 3,3-bis(1-methylimidazol-2-yl)propionate (L1) and its conjugate acid HL1 have been synthesised and structurally and spectroscopically characterised. The reaction of equimolar amounts of ligand and CuII resulted in the complexes [Cu(L1)]n(X)n (X=OTf-, PF6(-); n=1,2), for which a new bridging coordination mode of L1 is inferred. Although these complexes showed moderate catecholase activity in the oxidation of 3,5-di-tert-butylcatechol, surprising reactivity with the pseudo-substrate tetrachlorocatechol was observed. A chloranilato-bridged dinuclear CuII complex was isolated from the reaction of [Cu(L1)]n(PF6)n with tetrachlorocatechol. This stoichiometric oxidative double dehalogenation of tetrachlorocatechol to chloranilic acid by a biomimetic copper(II) complex is unprecedented. The crystal structure of the product, [Cu2(ca)Cl2(HL1)2], shows a bridging bis-bidentate chloranilato (ca) ligand and ligand L1 coordinated as its conjugate acid (HL1) in a tridentate fashion. Magnetic susceptibility studies revealed weak antiferromagnetic coupling (J= -35 cm(-1)) between the two copper centres in the dinuclear complex. Dissolution of the green complex [Cu2(ca)Cl2(HL1)2] resulted in the formation of new pink-purple mononuclear compound [Cu(ca)(HL1)(H2O)], the crystal structure of which was determined. It showed a terminal bidentate chloranilato ligand and N,N-bidentate coordination of ligand HL1, which illustrates the flexible coordination chemistry of ligand L1.     

Structural and electronic characterization of non-heme Fe(II)-nitrosyls as biomimetic models of the Fe(B) center of bacterial nitric oxide reductase

The detoxification of nitric oxide (NO) by bacterial NO reductase (NorBC) has gained much attention as this reaction provides a paradigm as to how NO can be detoxified anaerobically in cells. However, a clear mechanistic picture of how the heme/non-heme active site of NorBC activates NO is lacking, mostly as a result of insufficient knowledge about the properties of the non-heme iron(II)-NO adduct. Here we report the first biomimetic model complexes for this species that closely resemble the coordination environment found in the protein, using the ligands BMPA-Pr and TPA. The systematic investigation of these compounds allowed us to gain key insight into the electronic structure and geometric properties of high-spin non-heme iron(II)-NO adducts. In particular, we show how small changes in the ligand environment of iron could be used by NorBC to greatly modulate the properties, and hence, the reactivity of this species.     

Bidentate ligation of heme analogues; novel biomimetics of peroxidase active site

The multifunctional nature of proteins that have iron-heme cofactors with noncovalent histidine linkage to the protein is controlled by the heme environment. Previous studies of these active-site structures show that the primary difference is the length of the iron-proximal histidine bond, which can be controlled by the degree of H-bonding to this histidine. Great efforts to mimic these functions with synthetic analogues have been made for more than two decades. The peroxidase models resulted in several catalytic systems capable of a large range of oxidative transformations. Most of these model systems modified the porphyrin ring covalently by directly binding auxiliary elements that control and facilitate reactivity; for example, electron-donating or -withdrawing substituents. A biomimetic approach to enzyme mimicking would have taken a different route, by attempting to keep the porphyrin ring system unaltered, as close as possible to its native form, and introducing all modifications at or close to the axial coordination sites. Such a model system would be less demanding synthetically, would make it easy to study the effect of a single structural modification, and might even provide a way to probe effects resulting from porphyrin exchange. We introduce here an alternative model system based on these principles. It consists of a two component system: a bis-imidazolyl ligand and an iron-porphyrin (readily substituted by a hemin). All modifications were introduced only to the ligand that engulfs the porphyrin and binds to the iron's fifth and sixth coordination sites. We describe the design, synthesis, and characterization of nine different model compounds with increased complexity. The primary tool for characterizing the environment of each complex Fe(III) center was the Extended X-ray Absorption Fine Structure (EXAFS) measurements, supported by UV/Vis, IR, and NMR spectroscopy and by molecular modeling. Introduction of asymmetry, by attaching different imidazoles as head groups, led to the formation of two axial bonds of different length. Addition of H-bonds to one of the imidazoles in an advanced model increased this differentiation and expanded the porphyrin ring. These complexes were found to be almost identical in structure to peroxidase active sites. Similarly to the peroxidases and other synthetic models, these compounds stabilize the green, compound I-like intermediate, and catalyze the oxidation of organic substrates.     

Deconstructing Covalent Organocatalysis

Modern organocatalysis has rapidly evolved into an essential component of contemporary organic synthesis. One of the most distinctive aspects of organocatalytic processes is the biomimetic nature in which the catalyst engages the substrate, often forming covalently bound intermediates in a manner reminiscent of enzyme catalysis. Indeed, the process of intramolecularization is often accompanied by a conformational change of the catalyst scaffold, further accentuating this analogy with biological systems. The isolation and study of these catalytic intermediates facilitate the rapid generation of conformation and reactivity profiles to assist in organocatalytic reaction development and/or clarify reaction outcomes. Emulating the formative advances that have derived from studying reaction intermediates in mechanistic organometallic and enzymatic catalysis, the deconstruction of covalently bound organocatalysis intermediates is gaining momentum as a design strategy.     

Supramolecular allosteric cofacial porphyrin complexes

Nature routinely uses cooperative interactions to regulate cellular activity. For years, chemists have designed synthetic systems that aim toward harnessing the reactivity common to natural biological systems. By learning how to control these interactions in situ, one begins to allow for the preparation of man-made biomimetic systems that can efficiently mimic the interactions found in Nature. To this end, we have designed a synthetic protocol for the preparation of flexible metal-directed supramolecular cofacial porphyrin complexes which are readily obtained in greater than 90% yield through the use of new hemilabile porphyrin ligands with bifunctional ether-phosphine or thioether-phosphine substituents at the 5 and 15 positions on the porphyrin ring. The resulting architectures contain two hemilabile ligand-metal domains (RhI or CuI sites) and two cofacially aligned porphyrins (ZnII sites), offering orthogonal functionalities and allowing these multimetallic complexes to exist in two states, "condensed" or "open". Combining the ether-phosphine ligand with the appropriate RhI or CuI transition-metal precursors results in "open" macrocyclic products. In contrast, reacting the thioether-phosphine ligand with RhI or CuI precursors yields condensed structures that can be converted into their "open" macrocyclic forms via introduction of additional ancillary ligands. The change in cavity size that occurs allows these structures to function as allosteric catalysts for the acyl transfer reaction between X-pyridylcarbinol (where X = 2, 3, or 4) and 1-acetylimidazole. For 3- and 4-pyridylcarbinol, the "open" macrocycle accelerates the acyl transfer reaction more than the condensed analogue and significantly more than the porphyrin monomer. In contrast, an allosteric effect was not observed for 2-pyridylcarbinol, which is expected to be a weaker binder and is unfavorably constrained inside the macrocyclic cavity.     

Redox‐Active Ligand Assisted Catalytic Water Oxidation by a RuIV=O Intermediate

Water splitting is one of the most promising solutions for storing solar energy in a chemical bond. Water oxidation is still the bottleneck step because of its inherent difficulty and the limited understanding of the O?O bond formation mechanism. Molecular catalysts provide a platform for understanding this process in depth and have received wide attention since the first Ru‐based catalyst was reported in 1982. Ru^V=O is considered a key intermediate to initiate the O?O bond formation through either a water nucleophilic attack (WNA) pathway or a bimolecular coupling (I2M) pathway. Herein, we report a Ru‐based catalyst that displays water oxidation reactivity with Ru^IV=(O) with the help of a redox‐active ligand at pH 7.0. The results of electrochemical studies and DFT calculations disclose that ligand oxidation could significantly improve the reactivity of Ru^IV=O toward water oxidation. Under these conditions, sustained water oxidation catalysis occurs at reasonable rates with low overpotential (ca. 183 mV).     

Molecular Networks in Dynamic Multilevel Systems

Dynamic multilevel systems can be assembled from molecular building blocks through two or more reversible reactions that form covalent bonds. Molecular networks of dynamic multilevel systems can exhibit different connectivities between nodes. The design and creation of molecular networks in multilevel systems require control of the crossed reactivity of the functional groups (how to connect nodes) and the conditions of the reactions (when to connect nodes). In recent years, the combination of orthogonal and communicating reactions, which can be simultaneous or individually activated, has produced a variety of systems that have given rise to macrocycles and cages, as well as molecular motors and multicomponent architectures on surfaces. A given set of reactions can lead to systems with unique responsiveness, compositions, and functions as a result of the relative reactivities. In this Concept article, different molecular networks from synthetic systems that can be produced by combinations of different reaction types are discussed. Moreover, applications of this chemistry are highlighted, and future perspectives are envisioned.     

Direct Comparison of the Reactivity of Model Complexes for Compounds 0, I,and II in Oxygenation,Hydrogen‐Abstraction,and Hydride‐Transfer Processes

The iron(III) meso‐tetramesitylporphyrin complex is a good biomimetic to study the catalytic reactions of cytochrome P450. All of the three most discussed reactive intermediates concerning P450 catalysis (namely, Cpd 0, Cpd I, and Cpd II) can be selectively produced, identified, and stabilized for many minutes in solution at low temperature by choosing appropriate reaction conditions. In this way, their reactivity against various substrates was determined by utilizing low‐temperature rapid‐scan UV/Vis spectroscopy. Since all reactive intermediates are derived from a single model complex, the results of these kinetic measurements provide for the first time a full comparability of the determined rate constants for the three intermediates. The rate constants reveal a significant dependence of the reactivity on the type of reaction (e.g., oxygenation, hydrogen abstraction, or hydride transfer), which closely correlates with the chemical nature of Cpds 0, I, and II. The detailed knowledge of the reactivity of these intermediates provides a valuable tool to evaluate their particular role in biological systems.     

What factors influence the ratio of C-H hydroxylation versus C=C epoxidation by a nonheme cytochrome P450 biomimetic?

Density functional calculations on a nonheme biomimetic (Fe=O(TMCS+) have been performed and its catalytic properties versus propene investigated. Our studies show that this catalyst is able to chemoselectively hydroxylate C=H bonds even in the presence of C=C double bonds. This phenomenon has been analyzed and found to occur due to Pauli repusions between protons on the TMCS ligand with protons attached to the approaching substrate. The geometries of the rate determining transition states indicate that the steric hindrance is larger in the epoxidation transition states than in the hydroxylation ones with much shorter distances; hence the hydroxylation pathway is favored over the epoxidation. Although, the reactant experiences close lying triplet and quintet spin states, the dominant reaction mechanism takes place on the quintet spin state surface; i.e., Fe=O(TMCS)+ reacts via single-state reactivity. Our calculations show that this spin state selectivity is the result of geometric orientation of the transition state structures, whereby the triplet ones are destabilized by electrostatic repulsions between the substrate and the ligand while the quintet spin transition states are aligned along the ideal axis. The reactivity patterns and geometries are compared with oxoiron species of dioxygenase and monoxygenase enzymes. Thus, Fe=O(TMCS)+ shows some similarities with P450 enzyme reactivity: it chemoselectively hydroxylates C=H bonds even in the presence of a C=C double bond and therefore is an acceptable P450 biomimetic. However, the absolute barriers of substrate oxidation by Fe=O(TMCS)+ are higher than the ones obtained with heme enzymes, but the chemoselectivity is lesser affected by external perturbations such as hydrogen bonding of a methanol molecule toward the thiolate sulfur or a dielectric constant. This is the first oxoiron complex whereby we calculated a chemoselective hydroxylation over epoxidation in the gas phase.     

Structural-functional modeling of non-heme oxygenases

The nature designed metal-containing oxygenases to perform the most difficult oxidation reactions, such as the alkane oxidation, including the oxidation of methane, the most inert alkane. The enzymatic oxygenation, which proceeds under physiological conditions, i.e., in the absence of severe chemical treatment, is characterized by high efficiency and selectivity as yet unattainable in chemical processes. A search for chemical systems reproducing the prominent features of oxygenases is based on the structural-functional modeling of the active sites of these biocatalysts. Recent studies have shown that it is, in principle, possible to design biomimetic catalysts having as good characteristics as biocatalysts.     

Self-oscillating polymer gel as novel biomimetic materials exhibiting spatiotemporal structure

As a novel biomimetic polymer gel, we have been studying polymer gel with an autonomous self-oscillating function since it was firstly reported in 1996. For developing the polymer gels, we utilized an oscillating chemical reaction, called the Belousov?CZhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. The self-oscillating polymer gel is composed of a poly(N-isopropylacrylamide) network in which the metal catalyst for the BZ reaction is covalently immobilized. Under the coexistence of the reactants, the polymer undergoes spontaneous swelling?Cdeswelling changes (in the case of gel) or cyclic soluble?Cinsoluble changes (in the case of uncross-linked polymer) without any on?Coff switching of external stimuli. Several kinds of functional material systems utilizing the self-oscillating polymer and gel such as biomimetic actuators, mass transport surface, etc. are expected. Here, these recent progress on the self-oscillating polymer and gels and the design of functional material systems are summarized.