Secondary Coordination Sphere Interactions Research Articles

HYSCORE and QM/MM Studies of Second Sphere Variants of the Type 1 Copper Site in Azurin: Influence of Mutations on the Hyperfine Couplings of Remote Nitrogens.

Secondary coordination sphere (SCS) interactions have been shown to play important roles in tuning reduction potentials and electron transfer (ET) properties of the Type 1 copper proteins, but the precise roles of these interactions are not fully understood. In this work, we examined the influence of F114P, F114N, and N47S mutations in the SCS on the electronic structure of the T1 copper center in azurin (Az) by studying the hyperfine couplings of (i) histidine remote Nε nitrogens and (ii) the amide Np using the two-dimensional (2D) pulsed electron paramagnetic resonance (EPR) technique HYSCORE (hyperfine sublevel correlation) combined with quantum mechanics/molecular mechanics (QM/MM) and DLPNO-CCSD calculations. Our data show that some components of hyperfine tensor and isotropic coupling in N47SAz and F114PAz (but not F114NAz) deviate by up to ∼±20% from WTAz, indicating that these mutations significantly influence the spin density distribution between the CuII site and coordinating ligands. Furthermore, our calculations support the assignment of Np to the backbone amide of residue 47 (both in Asn and Ser variants). Since the spin density distributions play an important role in tuning the covalency of the Cu-Scys bond of Type 1 copper center that has been shown to be crucial in controlling the reduction potentials, this study provides additional insights into the electron spin factor in tuning the reduction potentials and ET properties.

Understanding the [NiFe] Hydrogenase Active Site Environment through Ultrafast Infrared and 2D-IR Spectroscopy of the Subsite Analogue K[CpFe(CO)(CN)2] in Polar and Protic Solvents.

The [CpFe(CO)(CN)2]- unit is an excellent structural model for the Fe(CO)(CN)2 moiety of the active site found in [NiFe] hydrogenases. Ultrafast infrared (IR) pump-probe and 2D-IR spectroscopy have been used to study K[CpFe(CO)(CN)2] (M1) in a range of protic and polar solvents and as a dry film. Measurements of anharmonicity, intermode vibrational coupling strength, vibrational relaxation time, and solvation dynamics of the CO and CN stretching modes of M1 in H2O, D2O, methanol, dimethyl sulfoxide, and acetonitrile reveal that H-bonding to the CN ligands plays an important role in defining the spectroscopic characteristics and relaxation dynamics of the Fe(CO)(CN)2 unit. Comparisons of the spectroscopic and dynamic data obtained for M1 in solution and in a dry film with those obtained for the enzyme led to the conclusion that the protein backbone forms an important part of the bimetallic active site environment via secondary coordination sphere interactions.

Probing secondary coordination sphere interactions within porphyrin-cored polymer nanoparticles

A suite of zinc porphyrin-cored polymeric nanoparticles were synthesized and characterized to study secondary coordination sphere interactions. We show that with proper design these materials catalyze the reaction of cyanide with N,N-dimethylformamide.

Direct Aerobic Generation of a Ferric Hydroperoxo Intermediate Via a Preorganized Secondary Coordination Sphere.

Enzymes exert control over the reactivity of metal centers with precise tuning of the secondary coordination sphere of active sites. One particularly elegant illustration of this principle is in the controlled delivery of proton and electron equivalents in order to activate abundant but kinetically inert oxidants such as O2 for oxidative chemistry. Chemists have drawn inspiration from biology in designing molecular systems where the secondary coordination sphere can shuttle protons or electrons to substrates. However, a biomimetic activation of O2 requires the transfer of both protons and electrons, and molecular systems where ancillary ligands are designed to provide both of these equivalents are comparatively rare. Here, we report the use of a dihydrazonopyrrole (DHP) ligand complexed to Fe to perform exactly such a biomimetic activation of O2. In the presence of O2, this complex directly generates a high spin Fe(III)-hydroperoxo intermediate which features a DHP• ligand radical via ligand-based transfer of an H atom. This system displays oxidative reactivity and ultimately releases hydrogen peroxide, providing insight on how secondary coordination sphere interactions influence the evolution of oxidizing intermediates in Fe-mediated aerobic oxidations.

Correction: Anion exchange-induced single-molecule dispersion of cobalt porphyrins in a cationic porous organic polymer for enhanced electrochemical CO2 reduction via secondary-coordination sphere interactions

Correction for ‘Anion exchange-induced single-molecule dispersion of cobalt porphyrins in a cationic porous organic polymer for enhanced electrochemical CO2 reduction via secondary-coordination sphere interactions’ by Jia-Kang Tang et al., J. Mater. Chem. A, 2020, DOI: 10.1039/d0ta07068h.

Anion exchange-induced single-molecule dispersion of cobalt porphyrins in a cationic porous organic polymer for enhanced electrochemical CO2 reduction via secondary-coordination sphere interactions

Anion exchange is a promising strategy to achieve synergistic catalysis via secondary coordination sphere interactions between the catalyst and the support.

Harnessing Secondary Coordination Sphere Interactions That Enable the Selective Amidation of Benzylic C-H Bonds.

Engineering site-selectivity is highly desirable especially in C-H functionalization reactions. We report a new catalyst platform that is highly selective for the amidation of benzylic C-H bonds controlled by π-π interactions in the secondary coordination sphere. Mechanistic understanding of the previously developed iridium catalysts that showed poor regioselectivity gave rise to the recognition that the π-cloud of an aromatic fragment on the substrate can act as a formal directing group through an attractive noncovalent interaction with the bidentate ligand of the catalyst. On the basis of this mechanism-driven strategy, we developed a cationic (η5-C5H5)Ru(II) catalyst with a neutral polypyridyl ligand to obtain record-setting benzylic selectivity in an intramolecular C-H lactamization in the presence of tertiary C-H bonds at the same distance. Experimental and computational techniques were integrated to identify the origin of this unprecedented benzylic selectivity, and robust linear free energy relationship between solvent polarity index and the measured site-selectivity was found to clearly corroborate that the solvophobic effect drives the selectivity. Generality of the reaction scope and applicability toward versatile γ-lactam synthesis were demonstrated.

Enhanced Rates of C-H Bond Cleavage by a Hydrogen-Bonded Synthetic Heme High-Valent Iron(IV) Oxo Complex.

Secondary coordination sphere interactions are critical in facilitating the formation, stabilization, and enhanced reactivity of high-valent oxidants required for essential biochemical processes. Herein, we compare the C-H bond oxidizing capabilities of spectroscopically characterized synthetic heme iron(IV) oxo complexes, F8Cmpd-II (F8 = tetrakis(2,6-difluorophenyl)porphyrinate), and a 2,6-lutidinium triflate (LutH+) Lewis acid adduct involving ferryl O-atom hydrogen-bonding, F8Cmpd-II(LutH+). Second-order rate constants utilizing C-H and C-D substrates were obtained by UV-vis spectroscopic monitoring, while products were characterized and quantified by EPR spectroscopy and gas chromatography (GC). With xanthene, F8Cmpd-II(LutH+) reacts 40 times faster (k2 = 14.2 M-1 s-1; -90 °C) than does F8Cmpd-II, giving bixanthene plus xanthone and the heme product [F8FeIIIOH2]+. For substrates with greater C-H bond dissociation energies (BDEs) F8Cmpd-II(LutH+) reacts with the second order rate constants k2(9,10-dihydroanthracene; DHA) = 0.485 M-1 s-1 and k2(fluorene) = 0.102 M-1 s-1 (-90 °C); by contrast, F8Cmpd-II is unreactive toward these substrates. For xanthene vs xanthene-(d2), large, nonclassical deuterium kinetic isotope effects are roughly estimated for both F8Cmpd-II and F8Cmpd-II(LutH+). The deuterated H-bonded analog, F8Cmpd-II(LutD+), was also prepared; for the reaction with DHA, an inverse KIE (compared to F8Cmpd-II(LutH+)) was observed. This work originates/inaugurates experimental investigation of the reactivity of authentic H-bonded heme-based FeIV═O compounds, critically establishing the importance of oxo H-bonding (or protonation) in heme complexes and enzyme active sites.

Understanding and Modulating Metalloenzymes with Unnatural Amino Acids, Non-Native Metal Ions, and Non-Native Metallocofactors.

Metalloproteins set the gold standard for performing important functions, including catalyzing demanding reactions under mild conditions. Designing artificial metalloenzymes (ArMs) to catalyze abiological reactions has been a major endeavor for many years, but most ArM activities are far below those of native enzymes, making them unsuitable for most pratical applications. A critical step to advance the field is to fundamentally understand what it takes to not only confer but also fine-tune ArM activities so they match those of native enzymes. Indeed, only once we can freely modulate ArM activity to rival (or surpass!) natural enzymes can the potential of ArMs be fully realized. A key to unlocking ArM potential is the observation that one metal primary coordination sphere can display a range of functions and levels of activity, leading to the realization that secondary coordination sphere (SCS) interactions are critically important. However, SCS interactions are numerous, long-range, and weak, making them very difficult to reproduce in ArMs. Furthermore, natural enzymes are tied to a small set of biologically available functional moieties from canonical amino acids and physiologically available metal ions and metallocofactors, severely limiting the chemical space available to probe and tune ArMs. In this Account, we summarize the use of unnatural amino acids (UAAs) and non-native metal ions and metallocofactors by our group and our collaborators to probe and modulate ArM functions. We incorporated isostructural UAAs in a type 1 copper (T1Cu) protein azurin to provide conclusive evidence that axial ligand hydrophobicity is a major determinant of T1Cu redunction potential ( E°'). Closely related work from other groups are also discussed. We also probed the role of protein backbone interactions that cannot be altered by standard mutagenesis by replacing the peptide bond with an ester linkage. We used insight gained from these studies to tune the E°' of azurin across the entire physiological range, the broadest range ever achieved in a single metalloprotein. Introducing UAA analogues of Tyr into ArM models of heme-copper oxidase (HCO) revealed a linear relationship between p Ka, E°', and activity. We also substituted non-native hemes and non-native metal ions for their native equivalents in these models to resolve several issues that were intractable in native HCOs and the closely related nitric oxide reductases, such as their roles in modulating substrate affinity, electron transfer rate, and activity. We incorporated abiological cofactors such as ferrocene and Mn(salen) into azurin and myoglobin, respectively, to stabilize these inorganic and organometallic compounds in water, confer abiological functions, tune their E°' and activity through SCS interactions, and show that the approach to metallocofactor anchoring and orientation can tune enantioselectivity and alter function. Replacing Cu in azurin with non-native Fe or Ni can impart novel activities, such as superoxide reduction and C-C bond formation. While progress was made, we have identified only a small fraction of the interactions that can be generally applied to ArMs to fine-tune their functions. Because SCS interactions are subtle and heavily interconnected, it has been difficult to characterize their effects quantitatively. It is vital to develop spectroscopic and computational techniques to detect and quantify their effects in both resting states and catalytic intermediates.

Versatile Rh- and Ir-Based Catalysts for CO2Hydrogenation, Formic Acid Dehydrogenation, and Transfer Hydrogenation of Quinolines

Considering the interest in processes related to hydrogen storage such as CO2 hydrogenation and formic acid (FA) decomposition, we have synthesized a set of Ir, Rh, or Ru complexes to be tested as versatile precatalysts in these reactions. In relation with the formation of H2 from FA, the possible applicability of these complexes in the transfer hydrogenation (TH) of challenging substrates as quinoline derivatives using FA/formate as hydrogen donor has also been addressed. Bearing in mind the importance of secondary coordination sphere interactions, N,N' ligands containing NH2 groups, coordinated or not to the metal center, were used. The general formula of the new complexes are [( p-cymene)RuCl(N,N')]X, X = Cl-, BF4- and [Cp*MCl(N,N')]Cl, M = Rh, Ir, where the N,N' ligands are 8-aminoquinoline (HL1), 6-pyridyl-2,4-diamine-1,3,5-triazine (L2) and 5-amino-1,10-phenanthroline (L3). Some complexes are not active or catalyze only one process. However, the complexes [Cp*MCl(HL1)]Cl with M = Rh, Ir are versatile catalysts that are active in hydrogenation of quinolines, FA decomposition, and also in CO2 hydrogenation with the iridium derivative being more active and robust. The CO2 hydrogenation takes place in mild conditions using only 5 bar of pressure of each gas (CO2 and H2). The behavior of some precatalysts in D2O and after the addition of 9 equiv of HCO2Na (pseudocatalytic conditions) has been studied in detail and mechanisms for the FA decomposition and the hydrogenation of CO2 have been proposed. For the Ru, Ir, or Rh complexes with ligand HL1, the amido species with the deprotonated ligand are observed. In the case of ruthenium, the formate complex is also detected. For the iridium derivative, both the amido intermediate and the hydrido species have been observed. This hydrido complex undergoes a process of umpolung D+↔ Ir-D. All in all, the results of this work reflect the active role of -NH2 in the transfer of H+.

Determination of the Molecular Structures of Ferric Enterobactin and Ferric Enantioenterobactin Using Racemic Crystallography.

Enterobactin is a secondary metabolite produced by Enterobacteriaceae for acquiring iron, an essential metal nutrient. The biosynthesis and utilization of enterobactin permits many Gram-negative bacteria to thrive in environments where low soluble iron concentrations would otherwise preclude survival. Despite extensive work carried out on this celebrated molecule since its discovery over 40 years ago, the ferric enterobactin complex has eluded crystallographic structural characterization. We report the successful growth of single crystals containing ferric enterobactin using racemic crystallization, a method that involves cocrystallization of a chiral molecule with its mirror image. The structures of ferric enterobactin and ferric enantioenterobactin obtained in this work provide a definitive assignment of the stereochemistry at the metal center and reveal secondary coordination sphere interactions. The structures were employed in computational investigations of the interactions of these complexes with two enterobactin-binding proteins, which illuminate the influence of metal-centered chirality on these interactions. This work highlights the utility of small-molecule racemic crystallography for obtaining elusive structures of coordination complexes.

The secondary coordination sphere and axial ligand effects on oxygen reduction reaction by iron porphyrins: a DFT computational study.

Oxygen reduction reaction (ORR) catalyzed by a bio-inspired iron porphyrin bearing a hanging carboxylic acid group over the porphyrin ring, and a tethered axial imidazole ligand was studied by DFT calculations. BP86 free energy calculations of the redox potentials and pK a's of reaction components involved in the proton coupled electron transfer (PCET) reactions of the ferric-hydroxo and -superoxo complexes were performed based on Born-Haber thermodynamic cycle in conjunction with a continuum solvation model. The comparison was made with iron porphyrins that lack either in the hanging acid group or axial ligand, suggesting that H-bond interaction between the carboxylic acid and iron-bound hydroxo, aquo, superoxo, and peroxo ligands (de)stabilizes the Fe-O bonding, resulting in the increase in the reduction potential of the ferric complexes. The axial ligand interaction with the imidazole raises the affinity of the iron-bound superoxo and peroxo ligands for proton. In addition, a low-spin end-on ferric-hydroperoxo intermediate, a key precursor for O-O cleavage, can be stabilized in the presence of axial ligation. Thus, selective and efficient ORR of iron porphyrin can be achieved with the aid of the secondary coordination sphere and axial ligand interactions.

Postsynthetic Systematic Electronic Tuning of Organoplatinum Photosensitizers via Secondary Coordination Sphere Interactions

In this work we show that postsynthetic addition of borane Lewis acids to Lewis base decorated organoplatinum photosensitizers induces significant changes in the optical and electrochemical properties. In particular, the charge transfer (CT) energies of these chromophores are significantly modified by these outer-sphere interactions. The direction of the CT shift depends on the site of Lewis acid binding, which occurs either at the diimine ligand in bipyrazine-linked molecules or at an ancillary acetylide ligand in pyridyl-substituted bis(acetylide) molecules. The magnitude of the shift depends on the Lewis acidity of the borane and the number of equivalents added and is comparable to the perturbation brought on by covalent substituent modification of supporting ligands in related complexes. This approach offers a new means of tuning the properties of organometallic phosphors that complements the traditional approach of covalent modification and other postsynthetic modification strategies.

Main Group Lewis Acid-Mediated Transformations of Transition-Metal Hydride Complexes.

This Review highlights stoichiometric reactions and elementary steps of catalytic reactions involving cooperative participation of transition-metal hydrides and main group Lewis acids. Included are reactions where the transition-metal hydride acts as a reactant as well as transformations that form the metal hydride as a product. This Review is divided by reaction type, illustrating the diverse roles that Lewis acids can play in mediating transformations involving transition-metal hydrides as either reactants or products. We begin with a discussion of reactions where metal hydrides form direct adducts with Lewis acids, elaborating the structure and dynamics of the products of these reactions. The bulk of this Review focuses on reactions where the transition metal and Lewis acid act in cooperation, and includes sections on carbonyl reduction, H2 activation, and hydride elimination reactions, all of which can be promoted by Lewis acids. Also included is a section on Lewis acid-base secondary coordination sphere interactions, which can influence the reactivity of hydrides. Work from the past 50 years is included, but the majority of this Review focuses on research from the past decade, with the intent of showcasing the rapid emergence of this field and the potential for further development into the future.

Localizing Perturbations of the Racemic Equilibria Involving Dipicolinate-Derived Lanthanide(III) Complexes.

Helical D3 tris(4-amino-2,6-pyridine-dicarboxylate)terbium(III) and europium(III) complexes, which form a racemic equilibrium in aqueous solution, were prepared to study their secondary coordination sphere interactions with chiral amino acids. These interactions were probed using a combination of circularly polarized luminescence (CPL) and 13C NMR spectroscopy. The results indicate that, regardless of the interaction between the chiral molecule and the complex, without an accessible hydrogen-bond donor on the associating molecule, perturbation of the racemic equilibrium cannot occur. A generalized conclusion is established that indicates that the mechanism of chiral recognition by tris(dipicolinate)lanthanide(III) complexes is similar across a variety of analogous ligands.

Design and fine-tuning redox potentials of metalloproteins involved in electron transfer in bioenergetics

Redox potentials are a major contributor in controlling the electron transfer (ET) rates and thus regulating the ET processes in the bioenergetics. To maximize the efficiency of the ET process, one needs to master the art of tuning the redox potential, especially in metalloproteins, as they represent major classes of ET proteins. In this review, we first describe the importance of tuning the redox potential of ET centers and its role in regulating the ET in bioenergetic processes including photosynthesis and respiration. The main focus of this review is to summarize recent work in designing the ET centers, namely cupredoxins, cytochromes, and iron–sulfur proteins, and examples in design of protein networks involved these ET centers. We then discuss the factors that affect redox potentials of these ET centers including metal ion, the ligands to metal center and interactions beyond the primary ligand, especially non-covalent secondary coordination sphere interactions. We provide examples of strategies to fine-tune the redox potential using both natural and unnatural amino acids and native and nonnative cofactors. Several case studies are used to illustrate recent successes in this area. Outlooks for future endeavors are also provided. This article is part of a Special Issue entitled Biodesign for Bioenergetics — the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

CO2 Hydrogenation Catalyzed by Iridium Complexes with a Proton-Responsive Ligand.

The catalytic cycle for the production of formic acid by CO2 hydrogenation and the reverse reaction have received renewed attention because they are viewed as offering a viable scheme for hydrogen storage and release. In this Forum Article, CO2 hydrogenation catalyzed by iridium complexes bearing sophisticated N^N-bidentate ligands is reported. We describe how a ligand containing hydroxy groups as proton-responsive substituents enhances the catalytic performance by an electronic effect of the oxyanions and a pendent-base effect through secondary coordination sphere interactions. In particular, [(Cp*IrCl)2(TH2BPM)]Cl2 (Cp* = pentamethylcyclopentadienyl; TH2BPM = 4,4',6,6'-tetrahydroxy-2,2'-bipyrimidine) enormously promotes the catalytic hydrogenation of CO2 in basic water by these synergistic effects under atmospheric pressure and at room temperature. Additionally, newly designed complexes with azole-type ligands were applied to CO2 hydrogenation. The catalytic efficiencies of the azole-type complexes were much higher than that of the unsubstituted bipyridine complex [Cp*Ir(bpy)(OH2)]SO4. Furthermore, the introduction of one or more hydroxy groups into ligands such as 2-pyrazolyl-6-hydroxypyridine, 2-pyrazolyl-4,6-dihydroxypyrimidine, and 4-pyrazolyl-2,6-dihydroxypyrimidine enhanced the catalytic activity. It is clear that the incorporation of additional electron-donating functionalities into proton-responsive azole-type ligands is effective for promoting further enhanced hydrogenation of CO2.

Redesigning the blue copper azurin into a redox-active mononuclear nonheme iron protein: preparation and study of Fe(II)-M121E azurin.

Much progress has been made in designing heme and dinuclear nonheme iron enzymes. In contrast, engineering mononuclear nonheme iron enzymes is lagging, even though these enzymes belong to a large class that catalyzes quite diverse reactions. Herein we report spectroscopic and X-ray crystallographic studies of Fe(II)-M121E azurin (Az), by replacing the axial Met121 and Cu(II) in wild-type azurin (wtAz) with Glu and Fe(II), respectively. In contrast to the redox inactive Fe(II)-wtAz, the Fe(II)-M121EAz mutant can be readily oxidized by Na2IrCl6, and interestingly, the protein exhibits superoxide scavenging activity. Mössbauer and EPR spectroscopies, along with X-ray structural comparisons, revealed similarities and differences between Fe(II)-M121EAz, Fe(II)-wtAz, and superoxide reductase (SOR) and allowed design of the second generation mutant, Fe(II)-M121EM44KAz, that exhibits increased superoxide scavenging activity by 2 orders of magnitude. This finding demonstrates the importance of noncovalent secondary coordination sphere interactions in fine-tuning enzymatic activity.

Hydrogen Evolution Catalyzed by Aluminum‐Bridged Cobalt Diglyoximate Complexes

AbstractThe syntheses of several cobalt diglyoximate complexes connected by one or two aluminum bridges are described. The aluminum centers are supported by tunable tetradentate diamine bisphenoxide ligands. Electrochemical investigations revealed that the number of aluminum bridges and the nature of the substituents on the phenoxide ligands significantly affect the cobalt reduction potentials. The present aluminum–cobalt compounds are electrocatalysts for proton reduction to hydrogen at potentials negative relative to those of the boron‐ and proton‐bridged analogs. The reported synthetic strategies allow modulation of the reduction potentials and the secondary coordination sphere interactions by tuning the ancillary ligands bound to aluminum.

Mechanistic Investigations and Secondary Coordination Sphere Effects in the Hydration of Nitriles with [Ru(η6-arene)Cl2PR3] Complexes

The mechanism of the nitrile-to-amide hydration reaction using [Ru(η6-arene)Cl2(PR3)] complexes as catalysts was investigated (η6-arene = C6H6, p-cymene, C6Me6; R = NMe2, OMe, OEt, Et, iPr). Experiments showed that the mechanism involves the following general sequence of reactions: substitution of a chloride ligand by the nitrile substrate, intermolecular nucleophilic attack by water to form an amidate intermediate, and dissociation of the resulting amide. The effects of secondary coordination sphere interactions on the rates and yields of the hydration reaction were investigated. Ligands that are capable of acting as hydrogen bond acceptors with the entering water molecule result in faster rates and higher yields than non-hydrogen-bonding ligands. The faster rates are attributable to the H-bonding-facilitated deprotonation of the water as the oxygen of the water bonds to the coordinated nitrile. DFT calculations on the proposed H-bonding intermediates support this interpretation. Most homogeneous catalys...