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Some pathogens use heme‐containing nitric oxide reductases (NORs) to reduce NO to N2O as their defense mechanism to detoxify NO and reduce nitrosative stress. This reduction is also significant in the global N cycle. Our previous experimental work showed that Fe and Co porphyrin NO complexes can couple with external NO to form N2O when activated by the Lewis acid BF3. A key difference from conventional two‐electron enzymatic reaction is that one electron is sufficient. However, a complete understanding of the entire reaction pathways and the more favorable reactivity for Fe remains unknown. Here, we present a quantum chemical study to provide such information. Our results confirmed Fe's higher experimental reactivity, showing advantages in all steps of the reaction pathway: easier metal oxidation for NO reduction and N−O cleavage as well as a larger size to expedite the N/O coordination mode transition. The Co system, with a similar product energy as the enzyme, shows potential for further development in catalytic NO coupling. This work also offers the first evidence that this new one‐electron NO reduction is both kinetically competitive and thermodynamically more favorable than the native pathway, supporting future initiatives in optimizing NO reduction agents in biology, environment, and industry. [ABSTRACT FROM AUTHOR]

Some bacterial heme proteins catalyze the coupling of two NO molecules to generate N2O. We previously reported that a heme Fe–NO model engages in this N−N bond‐forming reaction with NO. We now demonstrate that (OEP)CoII(NO) similarly reacts with 1 equiv of NO in the presence of the Lewis acids BX3 (X=F, C6F5) to generate N2O. DFT calculations support retention of the CoII oxidation state for the experimentally observed adduct (OEP)CoII(NO⋅BF3), the presumed hyponitrite intermediate (P.+)CoII(ONNO⋅BF3), and the porphyrin π‐radical cation by‐product of this reaction, and that the π‐radical cation formation likely occurs at the hyponitrite stage. In contrast, the Fe analogue undergoes a ferrous‐to‐ferric oxidation state conversion during this reaction. Our work shows that cobalt hemes are chemically competent to engage in the NO‐to‐N2O conversion reaction. [ABSTRACT FROM AUTHOR]

Bacterial NO reductase (bacNOR) enzymes utilize a heme/non-heme active site to couple two NO molecules to N2O. We show that BF3 coordination to the nitrosyl O-atom in (OEP)Fe(NO) activates it toward N-N bond formation with NO to generate N2O. 15N-isotopic labeling reveals a reversible nitrosyl exchange reaction and follow-up N-O bond cleavage in the N2O formation step. Other Lewis acids (B(C6F5)3 and K+) also promote the NO coupling reaction with (OEP)Fe(NO). These results, complemented by DFT calculations, provide experimental support for the cis:b3 pathway in bacNOR. [ABSTRACT FROM AUTHOR]

Heme-HNO species are crucial intermediates in several biological processes. To date, no well-defined Fe heme-HNO model compounds have been reported. Hydride attack on the cationic ferric [(OEP)Fe(NO)(5-MeIm)]OTf (OEP = octaethylporphyrinato dianion) generates an Fe-HNO product that has been characterized by IR and 1H NMR spectroscopy. Results of DFT calculations reveal a direct attack of the hydride on the N atom of the coordinated ferric nitrosyl. [ABSTRACT FROM AUTHOR]

High-quality solid-state 17O (I=5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing VIII ( S=1), CuII ( S=1/2), and MnIII ( S=2) metal centers, the 17O isotropic paramagnetic shifts were found to span a range of more than 10 000 ppm. In several cases, high-resolution 17O NMR spectra were recorded under very fast magic-angle spinning (MAS) conditions at 21.1 T. Quantum-chemical computations using density functional theory (DFT) qualitatively reproduced the experimental 17O hyperfine shift tensors. [ABSTRACT FROM AUTHOR]

Recent studies reported the development of biocatalytic heme carbenoid Si-H insertions for the selective formation of carbon-silicon bonds, but many mechanistic questions remain unaddressed. To this end, a DFT mechanistic investigation was performed which reveals an Fe II -based concerted hydride transfer mechanism with early transition state feature. The results from these computational analyses are consistent with experimental data of radical trapping, kinetic isotope effects, and structure-reactivity data using engineered variants of hemoproteins. Detailed geometric and electronic profiles along the heme catalyzed Si-H insertion pathways were provided to help understand the origin of experimental reactivity trends. Quantitative relationships between reaction barriers and some properties such as charge transfer from substrate to heme carbene and Si-H bond length change from reactant to transition state were found. Results suggest catalyst modifications to facilitate the charge transfer from the silane substrate to the carbene, which was determined to be a major electronic driving force of this reaction, should enable the development of improved biocatalysts for Si-H carbene insertion reactions.

Recent experimental reports of heme carbene C-H insertions show promising results for sustainable chemistry due to good yield and selectivity, low cost of iron, and low/no toxicity of hemes. But mechanistic details are mostly unknown. Despite structural similarity and isoelectronic nature between heme carbene and the Fe IV =O intermediate, our quantum chemical studies with detailed geometric and electronic information for the first time reveal an Fe II -based, concerted, hydride-transfer mechanism, which is different from the Fe IV -based stepwise hydrogen atom transfer mechanism for C-H functionalization by native heme enzymes. A trend of broad range experimental C-H insertion yields (0-88 %) of five different C-H bonds, including mostly non-functionalized moieties, was well reproduced. Results suggest that the substrate selectivity originates from the hydride formation capability. The predicted kinetic isotope effects were also in excellent agreement with experiment. Useful geometry, charge, and energy parameters well correlated with barriers were reported. These results provide the first theoretical evidence that carbene formation is the overall rate-limiting step, and suggest a key role of the formation of strong electrophilic heme carbene in developing heme-based C-H insertion catalysts and biocatalysts., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High-quality solid-state (17)O (I=5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing V(III) (S=1), Cu(II) (S=1/2), and Mn(III) (S=2) metal centers, the (17)O isotropic paramagnetic shifts were found to span a range of more than 10,000 ppm. In several cases, high-resolution (17)O NMR spectra were recorded under very fast magic-angle spinning (MAS) conditions at 21.1 T. Quantum-chemical computations using density functional theory (DFT) qualitatively reproduced the experimental (17)O hyperfine shift tensors., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous experimental and computational investigations show that the copper binding in the prion protein that is involved in a number of neurodegenerative diseases is complicated and the exact binding structures remain to be determined. To facilitate structural investigation in this field, we report a quantum chemical investigation of structural, EPR superhyperfine, and NMR hyperfine properties of various copper complexes of the octarepeat domain, which has several copies of highly conserved amino acid sequence of PHGGGWGQ. The predicted metal-ligand bond lengths of the X-ray structure of CuHGGGW, involving the central five residues in this domain, from the best method examined here, have a mean absolute deviation (MAD) of 0.030 Å, basically the same as found with experimental errors of various metal complexes. Prior controversial results regarding water coordination were resolved here with a more extensive computational investigation on 10 models with various water molecules and sequences (both HGGGW and PHGGGWGQ), which are consistent with the experimental reports. Experimental EPR superhyperfine constants are accurately reproduced with a MAD of 0.95 MHz. Results here suggest that the NMR hyperfine shifts which can be readily measured in NMR experiments and accurately predicted in quantum chemical calculations can provide more extensive and more sensitive structural probes than those from the current EPR studies. These results will be helpful for future experimental and computational investigations of the copper binding structures of the prion protein as well as other related systems., (© 2011 American Chemical Society)

Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years towards developing viable therapeutic agents for Alzheimer's disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages of aggregation possibly at the monomeric level, as oligomers are known to be neurotoxic. In this regard, exploiting the metal chelating property of Aβ to generate molecules that can overcome this impediment presents some promise. Recently, one such metal complex containing Pt(II) ([Pt(BPS)Cl(2)]) was reported to effectively inhibit Aβ42 aggregation and toxicity (1). This complex was able bind to Aβ42 at the N-terminal part of the peptide and triggered a conformational change resulting in effective inhibition. In the current report, we have generated a mixed-binuclear metal complex containing Pt(II) and Ru(II) that inhibited Aβ42 aggregation at an early stage of aggregation and seemed to have different modes of interaction than the previously reported Pt(II) complex, suggesting an important role of the second metal center. This 'proof-of-concept' compound will help in developing more effective molecules against Aβ aggregation by modifying the two metal centers as well as their ligands, which will open doors to new rationale for Aβ inhibition.