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1. A De Novo‐Designed Artificial Metallopeptide Hydrogenase: Insights into Photochemical Processes and the Role of Protonated Cys

   https://doi.org/10.1002/cssc.202100122  

   Malayam Parambath, Sreya ; Williams, Ashley E. ; Hunt, Leigh Anna ; Selvan, Dhanashree ; Hammer, Nathan I. ; Chakraborty, Saumen ( April 2021 , ChemSusChem)

   Hydrogenase enzymes produce H₂gas, which can be a potential source of alternative energy. Inspired by the [NiFe] hydrogenases, we report the construction of a de novo‐designed artificial hydrogenase (ArH). The ArH is a dimeric coiled coil where two cysteine (Cys) residues are introduced at tandema/dpositions of a heptad to create a tetrathiolato Ni binding site. Spectroscopic studies show that Ni binding significantly stabilizes the peptide producing electronic transitions characteristic of Ni‐thiolate proteins. The ArH produces H₂photocatalytically, demonstrating a bell‐shaped pH‐dependence on activity. Fluorescence lifetimes and transient absorption spectroscopic studies are undertaken to elucidate the nature of pH‐dependence, and to monitor the reaction kinetics of the photochemical processes. pH titrations are employed to determine the role of protonated Cys on reactivity. Through combining these results, a fine balance is found between solution acidity and the electron transfer steps. This balance is critical to maximize the production of Ni^I‐peptide and protonation of the Ni^II−H⁻intermediate (Ni−R) by a Cys (pK_a≈6.4) to produce H₂.

    

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2. MAHOMES II: A webserver for predicting if a metal binding site is enzymatic

   https://doi.org/10.1002/pro.4626  

   Feehan, Ryan ; Copeland, Matthew ; Franklin, Meghan W. ; Slusky, Joanna S. G. ( March 2023 , Protein Science)

   Recent advances have enabled high‐quality computationally generated structures for proteins with no solved crystal structures. However, protein function data remains largely limited to experimental methods and homology mapping. Since structure determines function, it is natural that methods capable of using computationally generated structures for functional annotations need to be advanced. Our laboratory recently developed a method to distinguish between metalloenzyme and nonenzyme sites. Here we report improvements to this method by upgrading our physicochemical features to alleviate the need for structures with sub‐angstrom precision and using machine learning to reduce training data labeling error. Our improved classifier identifies protein bound metal sites as enzymatic or nonenzymatic with 94% precision and 92% recall. We demonstrate that both adjustments increased predictive performance and reliability on sites with sub‐angstrom variations. We constructed a set of predicted metalloprotein structures with no solved crystal structures and no detectable homology to our training data. Our model had an accuracy of 90%–97.5% depending on the quality of the predicted structures included in our test. Finally, we found the physicochemical trends that drove this model's successful performance were local protein density, second shell ionizable residue burial, and the pocket's accessibility to the site. We anticipate that our model's ability to correctly identify catalytic metal sites could enable identification of new enzymatic mechanisms and improve de novo metalloenzyme design success rates.

    

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3. A Copper(II)‐Nitrite Complex Hydrogen‐Bonded to a Protonated Amine in the Second‐Coordination‐Sphere

   https://doi.org/10.1002/ejic.202200105  

   Gupta, Shourya ; Arora, Sumangla ; Mondal, Aditesh ; Stieber, S. Chantal E. ; Gupta, Puneet ; Kundu, Subrata ( May 2022 , European Journal of Inorganic Chemistry)

   Nitrous acid (HONO) plays pivotal roles in various metal‐free as well as metal‐mediated routes relevant to biogeochemistry, atmospheric chemistry, and mammalian physiology. While the metastable nature of HONO hinders the detailed investigations into its reactivity at a transition metal site, this report herein utilizes a heteroditopic copper(II) cryptate [oC]Cu^IIfeaturing a proton‐responsive second‐coordination‐sphere located at a suitable distance from a [Cu^II](ONO) core, thereby enabling isolation of a [Cu^II](κ¹‐ONO⋅⋅⋅H⁺) complex (2H‐NO₂). A set of complementary analytical studies (UV‐vis,¹⁴N/¹⁵N FTIR,¹⁵N NMR, HRMS, EPR, and CHN) on2H‐NO₂and its¹⁵N‐isotopomer (2H‐¹⁵NO₂) reveals the formulation of2H‐NO₂as {[oCH]Cu^II(κ¹‐ONO)}(ClO₄)₂. Non‐covalent interaction index (NCI) based on reduced density gradient (RDG) analysis on {[oCH]Cu^II(κ¹‐ONO)}²⁺discloses a H‐bonding interaction between the apical 3° ammonium site and the nitrite anion bound to the copper(II) site. The FTIR spectra of [Cu^II](κ¹‐ONO⋅⋅⋅H⁺) species (2H‐NO₂) shows a shift of ammonium NH vibrational feature to a lower wavenumber due to the H‐bonding interaction with nitrite. The reactivity profile of [Cu^II](κ¹‐ONO⋅⋅⋅H⁺) species (2H‐NO₂) towards anaerobic nitration of substituted phenol (2,4‐DTBP) is distinctly different relative to that of the closely related tripodal [Cu^II]‐nitrite complexes (1‐NO₂/3‐NO₂/4‐NO₂).

    

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4. Diverse Coordination Geometries Derived from Trisaminocyclohexane Ligands with Appended Outer‐Sphere Hydrogen Bond Donors

   https://doi.org/10.1002/ejic.202300434  

   Ekanayake, Danushka M. ; Sheridan, Patrick E. ; Lindeman, Sergey V. ; Fiedler, Adam T. ( September 2023 , European Journal of Inorganic Chemistry)

   With the aim of constructing hydrogen‐bonding networks in synthetic complexes, two new ligands derived fromcis,cis‐1,3,5‐triaminocyclohexane (TACH) have been prepared that feature pendant pyrrole or indole rings as outer‐sphere H‐bond donors. The TACH framework offers a facial arrangement of threeN‐donors, thereby mimicking common coordination motifs in the active sites of nonheme Fe and Cu enzymes. X‐ray structural characterization of a series of Cu^I‐X complexes (X=F, Cl, Br, NCS) revealed that these neutral ligands (H₃L^R, R=pyrrole or indole) coordinate in the intended facialN₃manner, yielding four‐coordinate complexes with idealizedC₃symmetry. The N−H units of the outer‐sphere heterocycles form a hydrogen‐bonding cavity around the axial (pseudo)halide ligand, as verified by crystallographic, spectroscopic, and computational analyses. Treatment of H₃L^pyrroleand H₃L^indolewith divalent transition metal chlorides (M^IICl₂, M=Fe, Cu, Zn) causes one heterocycle to deprotonate and coordinate to the M(II) center, giving rise to tetradentate ligands with two remaining outer‐sphere H‐bond donors. Further ligand deprotonation is observed upon reaction with Ni(II) and Cu(II) salts with weakly coordinating counteranions. The reported complexes highlight the versatility of TACH‐based ligands with pendant H‐bond donors, as the resulting scaffolds can support multiple protonation states, coordination geometries, and H‐bonding interactions.

    

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5. Atomically Dispersed Single Ni Site Catalysts for Nitrogen Reduction toward Electrochemical Ammonia Synthesis Using N 2 and H 2 O

   https://doi.org/10.1002/smtd.201900821  

   Mukherjee, Shreya ; Yang, Xiaoxuan ; Shan, Weitao ; Samarakoon, Widitha ; Karakalos, Stavros ; Cullen, David A. ; More, Karren ; Wang, Maoyu ; Feng, Zhenxing ; Wang, Guofeng ; et al ( February 2020 , Small Methods)

   Ammonia (NH₃) electrosynthesis gains significant attention as NH₃is essentially important for fertilizer production and fuel utilization. However, electrochemical nitrogen reduction reaction (NRR) remains a great challenge because of low activity and poor selectivity. Herein, a new class of atomically dispersed Ni site electrocatalyst is reported, which exhibits the optimal NH₃yield of 115 µg cm⁻²h⁻¹at –0.8 V versus reversible hydrogen electrode (RHE) under neutral conditions. High faradic efficiency of 21 ± 1.9% is achieved at ‐0.2 V versus RHE under alkaline conditions, although the ammonia yield is lower. The Ni sites are stabilized with nitrogen, which is verified by advanced X‐ray absorption spectroscopy and electron microscopy. Density functional theory calculations provide insightful understanding on the possible structure of active sites, relevant reaction pathways, and confirm that the Ni‐N₃sites are responsible for the experimentally observed activity and selectivity. Extensive controls strongly suggest that the atomically dispersed NiN₃site‐rich catalyst provides more intrinsically active sites than those in N‐doped carbon, instead of possible environmental contamination. This work further indicates that single‐metal site catalysts with optimal nitrogen coordination is very promising for NRR and indeed improves the scaling relationship of transition metals.

    

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