Amplifying reactivity of bio-inspired [FeFe]-hydrogenase mimics by organic nanotubes.

A bio-inspired FeFe hydrogenase model which catalyses hydrogen evolution reaction (HER) in acidic solutions is immobilized in polyaniline (PANI)-based nanotubes. A combination of analytical techniques reveals that this construct maintains both the molecular signatures of the bio-inspired complex and the material properties of PANI. The amine and imine-rich environment of the PANI chain amplifies the inherent HER activity of the bio-inspired complex, allowing electrocatalytic HER at neutral pH, with lower overpotentials and higher current densities compared to the bio-inspired complex alone. This construct retains the oxygen stability of the bio-inspired complex and remains stable through several hours of aerobic electrolysis, producing only 6.5% H2O2 from the competing oxygen reduction reaction (ORR).

Facile electrocatalytic proton reduction by a [Fe-Fe]-hydrogenase bio-inspired synthetic model bearing a terminal CN- ligand.

An azadithiolate bridged CN- bound pentacarbonyl bis-iron complex, mimicking the active site of [Fe-Fe] H2ase is synthesized. The geometric and electronic structure of this complex is elucidated using a combination of EXAFS analysis, infrared and Mössbauer spectroscopy and DFT calculations. The electrochemical investigations show that complex 1 effectively reduces H+ to H2 between pH 0-3 at diffusion-controlled rates (1011 M-1 s-1) i.e. 108 s-1 at pH 3 with an overpotential of 140 mV. Electrochemical analysis and DFT calculations suggests that a CN- ligand increases the pKa of the cluster enabling hydrogen production from its Fe(i)-Fe(0) state at pHs much higher and overpotential much lower than its precursor bis-iron hexacarbonyl model which is active in its Fe(0)-Fe(0) state. The formation of a terminal Fe-H species, evidenced by spectroelectrochemistry in organic solvent, via a rate determining proton coupled electron transfer step and protonation of the adjacent azadithiolate, lowers the kinetic barrier leading to diffusion controlled rates of H2 evolution. The stereo-electronic factors enhance its catalytic rate by 3 order of magnitude relative to a bis-iron hexacarbonyl precursor at the same pH and potential.

Low Potential CO2 Reduction by Inert Fe(II)-Macrobicyclic Complex: A New Concept of Cavity Assisted CO2 Activation.

The advantage of a pre-organized π-cavity of Fe(II) complex of a newly developed macrobicycle cryptand is explored for CO2 reduction by overcoming the problem of high overpotential associated with the inert nature of the cryptate. Thus, a bipyridine-centered tritopic macrobicycle having a molecular π-cavity capable of forming Fe(II) complex as well as potential for CO2 encapsulation is synthesized. The inert Fe(II)-cryptate shows much lower potential in cyclic voltammetry than the Fe(II)-tris-dimethylbipyridine (Fe-MBP) core. Interestingly, this cryptate shows electrochemical CO2 reduction at a considerably lower potential than the Fe-MBP inert core. Therefore, this study represents that a well-structured π-cavity may generate a new series of molecular catalysts for the CO2 reduction reaction (CO2 RR), even with the inert metal complexes.

Reduction of Sulfur Dioxide to Sulfur Monoxide by Ferrous Porphyrin.

The reduction of SO2 to fixed forms of sulfur can address the growing concerns regarding its detrimental effect on health and the environment as well as enable its valorization into valuable chemicals. The naturally occurring heme enzyme sulfite reductase (SiR) is known to reduce SO2 to H2 S and is an integral part of the global sulfur cycle. However, its action has not yet been mimicked in artificial systems outside of the protein matrix even after several decades of structural elucidation of the enzyme. While the coordination of SO2 to transition metals is documented, its reduction using molecular catalysts has remained elusive. Herein reduction of SO2 by iron(II) tetraphenylporphyrin is demonstrated. A combination of spectroscopic data backed up by theoretical calculations indicate that FeII TPP reduces SO2 by 2e- /2H+ to form an intermediate [FeIII -SO]+ species, also proposed for SiR, which releases SO. The SO obtained from the chemical reduction of SO2 could be evidenced in the form of a cheletropic adduct of butadiene resulting in an organic sulfoxide.

Second-Sphere Hydrogen-Bond Donors and Acceptors Affect the Rate and Selectivity of Electrochemical Oxygen Reduction by Iron Porphyrins Differently.

The factors that control the rate and selectivity of 4e-/4H+ O2 reduction are important for efficient energy transformation as well as for understanding the terminal step of respiration in aerobic organisms. Inspired by the design of naturally occurring enzymes which are efficient catalysts for O2 and H2O2 reduction, several artificial systems have been generated where different second-sphere residues have been installed to enhance the rate and efficiency of the 4e-/4H+ O2 reduction. These include hydrogen-bonding residues like amines, carboxylates, ethers, amides, phenols, etc. In some cases, improvements in the catalysis were recorded, whereas in some cases improvements were marginal or nonexistent. In this work, we use an iron porphyrin complex with pendant 1,10-phenanthroline residues which show a pH-dependent variation of the rate of the electrochemical O2 reduction reaction (ORR) over 2 orders of magnitude. In-situ surface-enhanced resonance Raman spectroscopy reveals the presence of different intermediates at different pH's reflecting different rate-determining steps at different pH's. These data in conjunction with density functional theory calculations reveal that when the distal 1,10-phenanthroline is neutral it acts as a hydrogen-bond acceptor which stabilizes H2O (product) binding to the active FeII state and retards the reaction. However, when the 1,10-phenanthroline is protonated, it acts as a hydrogen-bond donor which enhances O2 reduction by stabilizing FeIII-O2.- and FeIII-OOH intermediates and activating the O-O bond for cleavage. On the basis of these data, general guidelines for controlling the different possible rate-determining steps in the complex multistep 4e-/4H+ ORR are developed and a bioinspired principle-based design of an efficient electrochemical ORR is presented.

Bioinorganic Chemistry on Electrodes: Methods to Functional Modeling.

One of the major goals of bioinorganic chemistry has been to mimic the function of elegant metalloenzymes. Such functional modeling has been difficult to attain in solution, in particular, for reactions that require multiple protons and multiple electrons (nH+/ne-). Using a combination of heterogeneous electrochemistry, electrode and molecule design one may control both electron transfer (ET) and proton transfer (PT) of these nH+/ne- reactions. Such control can allow functional modeling of hydrogenases (H+ + e- → 1/2 H2), cytochrome c oxidase (O2 + 4 e- + 4 H+ → 2 H2O), monooxygenases (RR'CH2 + O2 + 2 e- + 2 H+ → RR'CHOH + H2O) and dioxygenases (S + O2 → SO2; S = organic substrate) in aqueous medium and at room temperatures. In addition, these heterogeneous constructs allow probing unnatural bioinspired reactions and estimation of the inner- and outer-sphere reorganization energy of small molecules and proteins.

A Bidirectional Bioinspired [FeFe]-Hydrogenase Model.

With the price-competitiveness of solar and wind power, hydrogen technologies may be game changers for a cleaner, defossilized, and sustainable energy future. H2 can indeed be produced in electrolyzers from water, stored for long periods, and converted back into power, on demand, in fuel cells. The feasibility of the latter process critically depends on the discovery of cheap and efficient catalysts able to replace platinum group metals at the anode and cathode of fuel cells. Bioinspiration can be key for designing such alternative catalysts. Here we show that a novel class of iron-based catalysts inspired from the active site of [FeFe]-hydrogenase behave as unprecedented bidirectional electrocatalysts for interconverting H2 and protons efficiently under near-neutral aqueous conditions. Such bioinspired catalysts have been implemented at the anode of a functional membrane-less H2/O2 fuel cell device.

Biochemical and artificial pathways for the reduction of carbon dioxide, nitrite and the competing proton reduction: effect of 2nd sphere interactions in catalysis.

Reduction of oxides and oxoanions of carbon and nitrogen are of great contemporary importance as they are crucial for a sustainable environment. Substantial research has been dedicated to these areas in the last few decades. These reductions require both electrons and protons and their thermodynamic potentials often make them compete with hydrogen evolution reaction i.e., the reaction of protons and electrons to generate H2. These reactions are abundant in the environment in microorganisms and are facilitated by naturally occurring enzymes. This review brings together the state-of-the-art knowledge in the area of enzymatic reduction of CO2, NO2- and H+ with those of artificial molecular electrocatalysis. A simple ligand field theory-based design principle for electrocatalysts is first described. The electronic structure considerations developed automatically yield the basic geometry required and the 2nd sphere interactions which can potentially aid the activation and the further reduction of these small molecules. A systematic review of the enzymatic reaction followed by those reported in artificial molecular electrocatalysts is presented for the reduction of CO2, NO2- and H+. The review is focused on mechanism of action of these metalloenzymes and artificial electrocatalysts and discusses general principles that guide the rates and product selectivity of these reactions. The importance of the 2nd sphere interactions in both enzymatic and artificial molecular catalysis is discussed in detail.

Oxygen Reduction by Iron Porphyrins with Covalently Attached Pendent Phenol and Quinol.

Phenols and quinols participate in both proton transfer and electron transfer processes in nature either in distinct elementary steps or in a concerted fashion. Recent investigations using synthetic heme/Cu models and iron porphyrins have indicated that phenols/quinols can react with both ferric superoxide and ferric peroxide intermediates formed during O2 reduction through a proton coupled electron transfer (PCET) process as well as via hydrogen atom transfer (HAT). Oxygen reduction by iron porphyrins bearing covalently attached pendant phenol and quinol groups is investigated. The data show that both of these can electrochemically reduce O2 selectively by 4e-/4H+ to H2O with very similar rates. However, the mechanism of the reaction, investigated both using heterogeneous electrochemistry and by trapping intermediates in organic solutions, can be either PCET or HAT and is governed by the thermodynamics of these intermediates involved. The results suggest that, while the reduction of the FeIII-O2̇- species to FeIII-OOH proceeds via PCET when a pendant phenol is present, it follows a HAT pathway with a pendant quinol. In the absence of the hydroxyl group the O2 reduction proceeds via an electron transfer followed by proton transfer to the FeIII-O2̇- species. The hydrogen bonding from the pendant phenol group to FeIII-O2̇- and FeIII-OOH species provides a unique advantage to the PCET process by lowering the inner-sphere reorganization energy by limiting the elongation of the O-O bond upon reduction.

A Single Iron Porphyrin Shows pH Dependent Switch between "Push" and "Pull" Effects in Electrochemical Oxygen Reduction.

The "push-pull" effects associated with heme enzymes manifest themselves through highly evolved distal amino acid environments and axial ligands to the heme. These conserved residues enhance their reactivities by orders of magnitude relative to small molecules that mimic the primary coordination. An instance of a mononuclear iron porphyrin with covalently attached pendent phenanthroline groups is reported which exhibit reactivity indicating a pH dependent "push" to "pull" transition in the same molecule. The pendant phenanthroline residues provide proton transfer pathways into the iron site, ensuring selective 4e-/4H+ reduction of O2 to water. The protonation of these residues at lower pH mimics the pull effect of peroxidases, and a coordination of an axial hydroxide ligand at high pH emulates the push effect of P450 monooxygenases. Both effects enhance the rate of O2 reduction by orders of magnitude over its value at neutral pH while maintaining exclusive selectivity for 4e-/4H+ oxygen reduction reaction.

Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions.

Emulating enzymatic reactivity using small molecules has been a long-time challenging pursuit of the scientific community. Peroxidases, ubiquitous heme enzymes that are involved in hormone synthesis and the immune system, have been a prime target of such efforts due to their tremendous potential in the chemical industry as well as in wastewater treatment. Here it is demonstrated that inclusion of a second sphere guanidine moiety in an iron porphyrin not only makes this small molecule a veritable peroxidase catalyst but also offers an auxiliary binding site for organic substrates, facilitating their rapid oxidation with a green oxidant like H2O2. This small molecule analogue exhibits a "ping-pong" mechanism and Michaelis-Menten type kinetics, which is generally typical of metallo-enzymes and follows a mechanism of the natural enzyme in its entirety, including the formation of compound I as the primary oxidant.

Natural products in parallel synthesis: triazole libraries of nonactic acid.

The synthesis of a library of nonactic acid-derived triazoloamide derivatives and their evaluation as antimicrobial agents is described.

4,5-Disubstituted oxazolidinones: High affinity molecular effectors of RNA function.

The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination function of the T box riboswitch.

A convenient approach for access to both carbapentofuranoses and carbahexopyranoses. Stereocontrolled synthesis of enantiopure carba-D-ribofuranoses, carba-D-arabinofuranoses and carba-L-gulopyranose.

A new approach to carbasugars in enantiomerically pure form is reported. The key step involves ring-closing metathesis of dienols 6 derived from a (R)-(+)-glyceraldehyde derivative 4 to form the substituted cyclopentenol 9 and cyclohexenol 34a. Stereocontrolled addition of hydroxyl groups followed by conversion of the ketal unit to hydroxymethyl group in these intermediates led to carbapentoses and -hexoses. Stereoselectivity during introduction of hydroxyl groups arises through the steric hindrance posed by the allylic substituents. A remarkable feature of the present approach is the accessibility of both d- and l-series of carbapentoses as illustrated by the synthesis of beta-D- and beta-L-carbaribofuranoses 17 and 20, respectively. Carba-alpha-D-ribofuranose 25, the biosynthetic intermediate to the antibiotic aristeromycin, has also been synthesized from the same cyclopentenol 9. Functional group manipulation in the cyclopentenol 9a also enabled access to carbaarabinofuranose 32. The present synthetic strategy can be extended for the synthesis of carbahexopyranose, as illustrated by the synthesis of carba-alpha-L-gulopyranose 40b.

Structure-activity studies of oxazolidinone analogs as RNA-binding agents.

We have synthesized and tested a series of novel 3,4,5-tri- and 4,5-disubstituted oxazolidinones for their ability to bind two structurally related T box antiterminator model RNAs. We have found that optimal binding selectivity is found in a small group of 4,5-disubstituted oxazolidinones.

Copper(I)-catalyzed intramolecular asymmetric [2 + 2] photocycloaddition. Synthesis of both enantiomers of cyclobutane derivatives.

[reaction: see text] A simple approach for asymmetric induction in Cu(I)-catalyzed [2 + 2] photocycloaddition, where asymmetric catalysts or chiral auxiliaries were inefficient, has been developed using the concept of chirality transfer from the readily available 2, 3-di-O-cyclohexylidine-(R)-(+)-glyceraldehyde. An anion-induced cleavage of the tetrahydrofuran ring of the resulting oxa-bicyclo[3.2.0]heptanes led to a convenient access to the synthetically useful cis-1,2-disubstituted cyclobutanes in enantiomerically pure form.