Ni2P active site ensembles tune electrocatalytic nitrate reduction selectivity.

We demonstrate that active site ensembles on transition metal phosphides tune the selectivity of the nitrate reduction reaction. Using Ni2P nanocrystals as a case study, we report a mechanism involving competitive co-adsorption of H* and NOx* intermediates. A near 100% faradaic efficiency for nitrate reduction over hydrogen evolution is observed at -0.4 V, while NH3 selectivity is maximized at -0.2 V vs. RHE.

Molecular mechanism of trehalose 6-phosphate inhibition of the plant metabolic sensor kinase SnRK1.

SUCROSE-NON-FERMENTING1-RELATED PROTEIN KINASE1 (SnRK1), a central plant metabolic sensor kinase, phosphorylates its target proteins, triggering a global shift from anabolism to catabolism. Molecular modeling revealed that upon binding of KIN10 to GEMINIVIRUS REP-INTERACTING KINASE1 (GRIK1), KIN10's activation T-loop reorients into GRIK1's active site, enabling its phosphorylation and activation. Trehalose 6-phosphate (T6P) is a proxy for cellular sugar status and a potent inhibitor of SnRK1. T6P binds to KIN10, a SnRK1 catalytic subunit, weakening its affinity for GRIK1. Here, we investigate the molecular details of T6P inhibition of KIN10. Molecular dynamics simulations and in vitro phosphorylation assays identified and validated the T6P binding site on KIN10. Under high-sugar conditions, T6P binds to KIN10, blocking the reorientation of its activation loop and preventing its phosphorylation and activation by GRIK1. Under these conditions, SnRK1 maintains only basal activity levels, minimizing phosphorylation of its target proteins, thereby facilitating a general shift from catabolism to anabolism.

Homologous acetone carboxylases select Fe(II) or Mn(II) as the catalytic cofactor.

Acetone carboxylases (ACs) catalyze the metal- and ATP-dependent conversion of acetone and bicarbonate to form acetoacetate. Interestingly, two homologous ACs that have been biochemically characterized have been reported to have different metal complements, implicating different metal dependencies in catalysis. ACs from proteobacteria Xanthobacter autotrophicus and Aromatoleum aromaticum share 68% sequence identity but have been proposed to have different catalytic metals. In this work, the two ACs were expressed under the same conditions in Escherichia coli and were subjected to parallel chelation and reconstitution experiments with Mn(II) or Fe(II). Electron paramagnetic and Mössbauer spectroscopies identified signatures, respectively, of Mn(II) or Fe(II) bound at the active site. These experiments showed that the respective ACs, without the assistance of chaperones, second metal sites, or post-translational modifications facilitate correct metal incorporation, and despite the expected thermodynamic preference for Fe(II), each preferred a distinct metal. Catalysis was likewise associated uniquely with the cognate metal, though either could potentially serve the proposed Lewis acidic role. Subtle differences in the protein structure are implicated in serving as a selectivity filter for Mn(II) or Fe(II).IMPORTANCEThe Irving-Williams series refers to the predicted stabilities of transition metal complexes where the observed general stability for divalent first-row transition metal complexes increase across the row. Acetone carboxylases (ACs) use a coordinated divalent metal at their active site in the catalytic conversion of bicarbonate and acetone to form acetoacetate. Highly homologous ACs discriminate among different divalent metals at their active sites such that variations of the enzyme prefer Mn(II) over Fe(II), defying Irving-Williams-predicted behavior. Defining the determinants that promote metal discrimination within the first-row transition metals is of broad fundamental importance in understanding metal-mediated catalysis and metal catalyst design.

Fe protein docking transduces conformational changes to MoFe nitrogenase active site in a nucleotide-dependent manner.

The reduction of dinitrogen to ammonia catalyzed by nitrogenase involves a complex series of events, including ATP hydrolysis, electron transfer, and activation of metal clusters for N2 reduction. Early evidence shows that an essential part of the mechanism involves transducing information between the nitrogenase component proteins through conformational dynamics. Here, millisecond time-resolved hydrogen-deuterium exchange mass spectrometry was used to unravel peptide-level protein motion on the time scale of catalysis of Mo-dependent nitrogenase from Azotobacter vinelandii. Normal mode analysis calculations complemented this data, providing insights into the specific signal transduction pathways that relay information across protein interfaces at distances spanning 100 Å. Together, these results show that conformational changes induced by protein docking are rapidly transduced to the active site, suggesting a specific mechanism for activating the metal cofactor in the enzyme active site.

A conformational equilibrium in the nitrogenase MoFe protein with an α-V70I amino acid substitution illuminates the mechanism of H2 formation.

Study of α-V70I-substituted nitrogenase MoFe protein identified Fe6 of FeMo-cofactor (Fe7S9MoC-homocitrate) as a critical N2 binding/reduction site. Freeze-trapping this enzyme during Ar turnover captured the key catalytic intermediate in high occupancy, denoted E4(4H), which has accumulated 4[e-/H+] as two bridging hydrides, Fe2-H-Fe6 and Fe3-H-Fe7, and protons bound to two sulfurs. E4(4H) is poised to bind/reduce N2 as driven by mechanistically-coupled H2 reductive-elimination of the hydrides. This process must compete with ongoing hydride protonation (HP), which releases H2 as the enzyme relaxes to state E2(2H), containing 2[e-/H+] as a hydride and sulfur-bound proton; accumulation of E4(4H) in α-V70I is enhanced by HP suppression. EPR and 95Mo ENDOR spectroscopies now show that resting-state α-V70I enzyme exists in two conformational states, both in solution and as crystallized, one with wild type (WT)-like FeMo-co and one with perturbed FeMo-co. These reflect two conformations of the Ile residue, as visualized in a reanalysis of the X-ray diffraction data of α-V70I and confirmed by computations. EPR measurements show delivery of 2[e-/H+] to the E0 state of the WT MoFe protein and to both α-V70I conformations generating E2(2H) that contains the Fe3-H-Fe7 bridging hydride; accumulation of another 2[e-/H+] generates E4(4H) with Fe2-H-Fe6 as the second hydride. E4(4H) in WT enzyme and a minority α-V70I E4(4H) conformation as visualized by QM/MM computations relax to resting-state through two HP steps that reverse the formation process: HP of Fe2-H-Fe6 followed by slower HP of Fe3-H-Fe7, which leads to transient accumulation of E2(2H) containing Fe3-H-Fe7. In the dominant α-V70I E4(4H) conformation, HP of Fe2-H-Fe6 is passively suppressed by the positioning of the Ile sidechain; slow HP of Fe3-H-Fe7 occurs first and the resulting E2(2H) contains Fe2-H-Fe6. It is this HP suppression in E4(4H) that enables α-V70I MoFe to accumulate E4(4H) in high occupancy. In addition, HP suppression in α-V70I E4(4H) kinetically unmasks hydride reductive-elimination without N2-binding, a process that is precluded in WT enzyme.

Mechanistic investigation of SARS-CoV-2 main protease to accelerate design of covalent inhibitors.

Targeted covalent inhibition represents one possible strategy to block the function of SARS-CoV-2 Main Protease (MPRO), an enzyme that plays a critical role in the replication of the novel SARS-CoV-2. Toward the design of covalent inhibitors, we built a covalent inhibitor dataset using deep learning models followed by high throughput virtual screening of these candidates against MPRO. Two top-ranking inhibitors were selected for mechanistic investigations-one with an activated ester warhead that has a piperazine core and the other with an acrylamide warhead. Specifically, we performed a detailed analysis of the free energetics of covalent inhibition by hybrid quantum mechanics/molecular mechanics simulations. Cleavage of a fragment of the non-structured protein (NSP) from the SARS-CoV-2 genome was also simulated for reference. Simulations show that both candidates form more stable enzyme-inhibitor (E-I) complexes than the chosen NSP. It was found that both the NSP fragment and the activated ester inhibitor react with CYS145 of MPRO in a concerted manner, whereas the acrylamide inhibitor follows a stepwise mechanism. Most importantly, the reversible reaction and the subsequent hydrolysis reaction from E-I complexes are less probable when compared to the reactions with an NSP fragment, showing promise for these candidates to be the base for efficient MPRO inhibitors.

Modeling Absolute Redox Potentials of Ferrocene in the Condensed Phase.

Absolute thermodynamic quantities for critical chemical reactions are needed to determine the role of solvents and reactive environments in catalysis and electrocatalysis. Theoretical methods can provide such quantification but are often hindered by the innate complexity of electron correlation and dynamic relaxation of solvent environments. We present and validate a protocol for calculating the redox potentials of the ferrocene/ferrocenium redox pair in acetonitrile. Equation-of-motion and effective fragment potential (EFP) methods are used to characterize the adiabatic and vertical ionization potentials as well as the electron affinity processes. We benchmark molecular mechanics against the EFP model to show the differences in the ferrocene electronic polarizability in two redox states. Our best estimate of the redox potential (4.94 eV) agrees well with the experimental value (4.93 eV). This demonstrates the ability of modern computational methods to predict absolute redox potentials quantitatively and to quantify the correlation of dynamic effects, which underlie their origin.

13C ENDOR Characterization of the Central Carbon within the Nitrogenase Catalytic Cofactor Indicates That the CFe6 Core Is a Stabilizing "Heart of Steel".

Substrates and inhibitors of Mo-dependent nitrogenase bind and react at Fe ions of the active-site FeMo-cofactor [7Fe-9S-C-Mo-homocitrate] contained within the MoFe protein α-subunit. The cofactor contains a CFe6 core, a carbon centered within a trigonal prism of six Fe, whose role in catalysis is unknown. Targeted 13C labeling of the carbon enables electron-nuclear double resonance (ENDOR) spectroscopy to sensitively monitor the electronic properties of the Fe-C bonds and the spin-coupling scheme adopted by the FeMo-cofactor metal ions. This report compares 13CFe6 ENDOR measurements for (i) the wild-type protein resting state (E0; α-Val70) to those of (ii) α-Ile70, (iii) α-Ala70-substituted proteins; (iv) crystallographically characterized CO-inhibited "hi-CO" state; (v) E4(4H) Janus intermediate, activated for N2 binding/reduction by accumulation of 4[e-/H+]; (vi) E4(2H)* state containing a doubly reduced FeMo-cofactor without Fe-bound substrates; and (vii) propargyl alcohol reduction intermediate having allyl alcohol bound as a ferracycle to FeMo-cofactor Fe6. All states examined, both S = 1/2 and 3/2 exhibited near-zero 13C isotropic hyperfine coupling constants, Ca = [-1.3 ↔ +2.7] MHz. Density functional theory computations and natural bond orbital analysis of the Fe-C bonds show that this occurs because a (3 spin-up/3 spin-down) spin-exchange configuration of CFe6 Fe-ion spins produces cancellation of large spin-transfers to carbon in each Fe-C bond. Previous X-ray diffraction and DFT both indicate that trigonal-prismatic geometry around carbon is maintained with high precision in all these states. The persistent structure and Fe-C bonding of the CFe6 core indicate that it does not provide a functionally dynamic (hemilabile) "beating heart"─instead it acts as "a heart of steel", stabilizing the structure of the FeMo-cofactor-active site during nitrogenase catalysis.

Hydrogen Atom Abstraction from an OsII(NH3)2 Complex Generates an OsIV(NH2)2 Complex: Experimental and Computational Analysis of the N-H Bond Dissociation Free Energies and Reactivity.

Double hydrogen atom abstraction from (TMP)OsII(NH3)2 (TMP = tetramesitylporphyrin) with phenoxyl or nitroxyl radicals leads to (TMP)OsIV(NH2)2. This unusual bis(amide) complex is diamagnetic and displays an N-H resonance at 12.0 ppm in its 1H NMR spectrum. 1H-15N correlation experiments identified a 15N NMR spectroscopic resonance signal at -267 ppm. Experimental reactivity studies and density functional theory calculations support relatively weak N-H bonds of 73.3 kcal/mol for (TMP)OsII(NH3)2 and 74.2 kcal/mol for (TMP)OsIII(NH3)(NH2). Cyclic voltammetry experiments provide an estimate of the pKa of [(TMP)OsIII(NH3)2]+. In the presence of Barton's base, a current enhancement is observed at the Os(III/II) couple, consistent with an ECE event. Spectroscopic experiments confirmed (TMP)OsIV(NH2)2 as the product of bulk electrolysis. Double hydrogen atom abstraction is influenced by π donation from the amides of (TMP)OsIV(NH2)2 into the d orbitals of the Os center, favoring the formation of (TMP)OsIV(NH2)2 over N-N coupling. This π donation leads to a Jahn-Teller distortion that splits the energy levels of the dxz and dyz orbitals of Os, results in a low-spin electron configuration, and leads to minimal aminyl character on the N atoms, rendering (TMP)OsIV(NH2)2 unreactive toward amide-amide coupling.

Multilevel Computational Studies Reveal the Importance of Axial Ligand for Oxygen Reduction Reaction on Fe-N-C Materials.

The systematic improvement of Fe-N-C materials for fuel cell applications has proven challenging, due in part to an incomplete atomistic understanding of the oxygen reduction reaction (ORR) under electrochemical conditions. Herein, a multilevel computational approach, which combines ab initio molecular dynamics simulations and constant potential density functional theory calculations, is used to assess proton-coupled electron transfer (PCET) processes and adsorption thermodynamics of key ORR intermediates. These calculations indicate that the potential-limiting step for ORR on Fe-N-C materials is the formation of the FeIII-OOH intermediate. They also show that an active site model with a water molecule axially ligated to the iron center throughout the catalytic cycle produces results that are consistent with the experimental measurements. In particular, reliable prediction of the ORR onset potential and the Fe(III/II) redox potential associated with the conversion of FeIII-OH to FeII and desorbed H2O requires an axial H2O co-adsorbed to the iron center. The observation of a five-coordinate rather than four-coordinate active site has significant implications for the thermodynamics and mechanism of ORR. These findings highlight the importance of solvent-substrate interactions and surface charge effects for understanding the PCET reaction mechanisms and transition-metal redox couples under realistic electrochemical conditions.

Weakening the N-H Bonds of NH3 Ligands: Triple Hydrogen-Atom Abstraction to Form a Chromium(V) Nitride.

Weakening and cleaving N-H bonds is crucial for improving molecular ammonia (NH3) oxidation catalysts. We report the synthesis and H-atom-abstraction reaction of bis(ammonia)chromium porphyrin complexes Cr(TPP)(NH3)2 and Cr(TMP)(NH3)2 (TPP = 5,10,15,20-tetraphenyl-meso-porphyrin and TMP = 5,10,15,20-tetramesityl-meso-porphyrin) using bulky aryloxyl radicals. The triple H-atom-abstraction reaction results in the formation of CrV(por)(≡N), with the nitride derived from NH3, as indicated by UV-vis and IR and single-crystal structural determination of Cr(TPP)(≡N). Subsequent oxidation of this chromium(V) nitrido complex results in the formation of CrIII(por), with scission of the Cr≡N bond. Computational analysis illustrates the progression from CrII to CrV and evaluates the energetics of abstracting H atoms from CrII-NH3 to generate CrV≡N. The formation and isolation of CrV(por)(≡N) illustrates the stability of these species and the need to chemically activate the nitride ligand for atom transfer or N-N coupling reactivity.

Molecular Catalysts with Diphosphine Ligands Containing Pendant Amines.

Pendant amines play an invaluable role in chemical reactivity, especially for molecular catalysts based on earth-abundant metals. As inspired by [FeFe]-hydrogenases, which contain a pendant amine positioned for cooperative bifunctionality, synthetic catalysts have been developed to emulate this multifunctionality through incorporation of a pendant amine in the second coordination sphere. Cyclic diphosphine ligands containing two amines serve as the basis for a class of catalysts that have been extensively studied and used to demonstrate the impact of a pendant base. These 1,5-diaza-3,7-diphosphacyclooctanes, now often referred to as "P2N2" ligands, have profound effects on the reactivity of many catalysts. The resulting [Ni(PR2NR'2)2]2+ complexes are electrocatalysts for both the oxidation and production of H2. Achieving the optimal benefit of the pendant amine requires that it has suitable basicity and is properly positioned relative to the metal center. In addition to the catalytic efficacy demonstrated with [Ni(PR2NR'2)2]2+ complexes for the oxidation and production of H2, catalysts with diphosphine ligands containing pendant amines have also been demonstrated for several metals for many different reactions, both in solution and immobilized on surfaces. The impact of pendant amines in catalyst design continues to expand.

Regioselectivity mechanism of the Thunbergia alata Δ6-16:0-acyl carrier protein desaturase.

Plant plastidial acyl-acyl carrier protein (ACP) desaturases are a soluble class of diiron-containing enzymes that are distinct from the diiron-containing integral membrane desaturases found in plants and other organisms. The archetype of this class is the stearoyl-ACP desaturase which converts stearoyl-ACP into oleoyl (18:1Δ9cis)-ACP. Several variants expressing distinct regioselectivity have been described including a Δ6-16:0-ACP desaturase from black-eyed Susan vine (Thunbergia alata). We solved a crystal structure of the T. alata desaturase at 2.05 Å resolution. Using molecular dynamics (MD) simulations, we identified a low-energy complex between 16:0-ACP and the desaturase that would position C6 and C7 of the acyl chain adjacent to the diiron active site. The model complex was used to identify mutant variants that could convert the T. alata Δ6 desaturase to Δ9 regioselectivity. Additional modeling between ACP and the mutant variants confirmed the predicted regioselectivity. To validate the in-silico predictions, we synthesized two variants of the T. alata desaturase and analyzed their reaction products using gas chromatography-coupled mass spectrometry. Assay results confirmed that mutants designed to convert T. alata Δ6 to Δ9 selectivity exhibited the predicted changes. In complementary experiments, variants of the castor desaturase designed to convert Δ9 to Δ6 selectivity lost some of their Δ9 desaturation ability and gained the ability to desaturate at the Δ6 position. The computational workflow for revealing the mechanistic understanding of regioselectivity presented herein lays a foundation for designing acyl-ACP desaturases with novel selectivities to increase the diversity of monoenes available for bioproduct applications.

Protonation of Serine in Gas and Condensed and Microsolvated States in Aqueous Solution.

Identification of molecules and elucidation of their chemical structure are ubiquitous problems in chemistry. Mass spectrometry (MS) can be used due to its sensitivity and versatility. For detection to occur, analytes must be ionized and transferred to the gas phase. Soft ionization processes such as electrospray ionization are popular; however, resulting microsolvated phases can alter the chemistry of analytes and therefore detection and identification. To understand these processes, we use computational methods to probe the ionization propensity of serine in the gas phase, aqueous microsolvated clusters, and aqueous solution. We show that the tautomeric form of serine is altered by the presence of water, as five water molecules can stabilize the zwitterionic tautomer. Inclusion of cosolutes such as ions can stabilize the zwitterion with as few as one or two water molecules present. We demonstrate that ionization propensity, as measured by gas phase bacisity, can increase by over 100 kJ/mol when placed in a small water-serine cluster, showing the sensitivity of the chemistry of microsolvated analytes. Finally, detailed analysis reveals that small droplets (less than seven water molecules) are extremely sensitive to addition of further water molecules. Beyond this limit, structural and electronic properties change little with droplet size.

Quantitative Account of the Bonding Properties of a Rubredoxin Model Complex [Fe(SCH3)4]q, q = -2, -1, +2, +3.

Iron-sulfur clusters play important roles in biology as parts of electron-transfer chains and catalytic cofactors. Here, we report a detailed computational analysis of a structural model of the simplest natural iron-sulfur cluster of rubredoxin and its cationic counterparts. Specifically, we investigated adiabatic reduction energies, dissociation energies, and bonding properties of the low-lying electronic states of the complexes [Fe(SCH3)4]2-/1-/2+/3+ using multireference (CASSCF, MRCISD), and coupled cluster [CCSD(T)] methodologies. We show that the nature of the Fe-S chemical bond and the magnitude of the ionization potentials in the anionic and cationic [Fe(SCH3)4] complexes offer a physical rationale for the relative stabilization, structure, and speciation of these complexes. Anionic and cationic complexes present different types of chemical bonds: prevalently ionic in [Fe(SCH3)4]2-/1- complexes and covalent in [Fe(SCH3)4]2+/3+ complexes. The ionic bonds result in an energy gain for the transition [Fe(SCH3)4]2- → [Fe(SCH3)4]- (i.e., FeII → FeIII) of 1.5 eV, while the covalent bonds result in an energy loss for the transition [Fe(SCH3)4]2+ → [Fe(SCH3)4]3+ of 16.6 eV, almost half of the ionization potential of Fe2+. The ionic versus covalent bond character influences the Fe-S bond strength and length, that is, ionic Fe-S bonds are longer than covalent ones by about 0.2 Š(for FeII) and 0.04 Š(for FeII). Finally, the average Fe-S heterolytic bond strength is 6.7 eV (FeII) and 14.6 eV (FeIII) at the RCCSD(T) level of theory.

Nickel-Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer.

Methyl-coenzyme M reductase (MCR) catalyzes both the synthesis and the anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of cofactor F430. The Ni ion, in its low-valent Ni(I) state, lights the fuse leading to homolysis of the C-S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. On the basis of the crystal structures, which reveal a Ni-thiol interaction between Ni(II)-MCR and inhibitor CoMSH, a Ni(I)-thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)-disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)-sulfur interaction poses a conundrum for the proposed hydrogen-atom abstraction reaction because the >6 Å distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears to be too long for such a reaction. The spectroscopic, kinetic, structural, and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)-N/O complex, not Ni(I)-S. These studies rule out direct Ni(I)-sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both the forward and the reverse MCR reactions emanate through long-range electron transfer from the Ni(I)-sulfonate complexes with methyl-SCoM and CoMSSCoB, respectively.

Mechanical coupling in the nitrogenase complex.

The enzyme nitrogenase reduces dinitrogen to ammonia utilizing electrons, protons, and energy obtained from the hydrolysis of ATP. Mo-dependent nitrogenase is a symmetric dimer, with each half comprising an ATP-dependent reductase, termed the Fe Protein, and a catalytic protein, known as the MoFe protein, which hosts the electron transfer P-cluster and the active-site metal cofactor (FeMo-co). A series of synchronized events for the electron transfer have been characterized experimentally, in which electron delivery is coupled to nucleotide hydrolysis and regulated by an intricate allosteric network. We report a graph theory analysis of the mechanical coupling in the nitrogenase complex as a key step to understanding the dynamics of allosteric regulation of nitrogen reduction. This analysis shows that regions near the active sites undergo large-scale, large-amplitude correlated motions that enable communications within each half and between the two halves of the complex. Computational predictions of mechanically regions were validated against an analysis of the solution phase dynamics of the nitrogenase complex via hydrogen-deuterium exchange. These regions include the P-loops and the switch regions in the Fe proteins, the loop containing the residue ß-188Ser adjacent to the P-cluster in the MoFe protein, and the residues near the protein-protein interface. In particular, it is found that: (i) within each Fe protein, the switch regions I and II are coupled to the [4Fe-4S] cluster; (ii) within each half of the complex, the switch regions I and II are coupled to the loop containing ß-188Ser; (iii) between the two halves of the complex, the regions near the nucleotide binding pockets of the two Fe proteins (in particular the P-loops, located over 130 Å apart) are also mechanically coupled. Notably, we found that residues next to the P-cluster (in particular the loop containing ß-188Ser) are important for communication between the two halves.

Atomistic insight on structure and dynamics of spinach acyl carrier protein with substrate length.

The plant acyl-acyl carrier protein (ACP) desaturases are a family of soluble enzymes that convert saturated fatty acyl-ACPs into their cis-monounsaturated equivalents in an oxygen-dependent reaction. These enzymes play a key role in biosynthesis of monounsaturated fatty acids in plants. ACPs are central proteins in fatty acid biosynthesis that deliver acyl chains to desaturases. They have been reported to show a varying degree of local dynamics and structural variability depending on the acyl chain size. It has been suggested that substrate-specific changes in ACP structure and dynamics have a crucial impact on the desaturase enzymatic activity. Using molecular dynamics simulations, we investigated the intrinsic solution structure and dynamics of ACP from spinach with four different acyl chains: capric (C10), myristic (C14), palmitic (C16), and stearic (C18) acids. We found that the fatty acids can adopt two distinct structural binding motifs, which feature different binding free energies and influence the ACP dynamics in a different manner. Docking simulations of ACP to castor Δ9-desaturase and ivy Δ4-desaturase suggest that ACP desaturase interactions could lead to a preferential selection between the motifs.

Catalytic bias in oxidation-reduction catalysis.

Cataytic bias refers to the propensity of a reaction catalyst to effect a different rate acceleration in one direction versus the other in a chemical reaction under non-equilibrium conditions. In biocatalysis, the inherent bias of an enzyme is often advantagous to augment the innate thermodynamics of a reaction to promote efficiency and fidelity in the coordination of catabolic and anabolic pathways. In industrial chemical catalysis a directional cataltyic bias is a sought after property in facilitating the engineering of systems that couple catalysis with harvest and storage of for example fine chemicals or energy compounds. Interestingly, there is little information about catalytic bias in biocatalysis likely in large part due to difficulties in developing tractible assays sensitive enough to study detailed kinetics. For oxidation-reduction reactions, colorimetric redox indicators exist in a range of reduction potentials to provide a mechanism to study both directions of reactions in a fairly facile manner. The current short review attempts to define catalytic bias conceptually and to develop model systems for defining the parameters that control catalytic bias in enzyme catalyzed oxidation-reduction catalysis.

Splitting of multiple hydrogen molecules by bioinspired diniobium metal complexes: a DFT study.

Splitting of molecular hydrogen (H2) into bridging and terminal hydrides is a common step in transition metal chemistry. Herein, we propose a novel organometallic platform for cleavage of multiple H2 molecules, which combines metal centers capable of stabilizing multiple oxidation states, and ligands bearing positioned pendant basic groups. Using quantum chemical modeling, we show that low-valent, early transition metal diniobium(ii) complexes with diphosphine ligands featuring pendant amines can favorably uptake up to 8 hydrogen atoms, and that the energetics are favored by the formation of intramolecular dihydrogen bonds. This result suggests new possible strategies for the development of hydrogen scavenger molecules that are able to perform reversible splitting of multiple H2 molecules.