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1. Analyzing mechanisms in Co( i ) redox catalysis using a pattern recognition platform

   https://doi.org/10.1039/d0sc06725c  

   Tang, Tianhua; Sandford, Christopher; Minteer, Shelley D.; Sigman, Matthew S. (April 2021, Chemical Science)

   null (Ed.)

   Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. The appropriate choice of redox mediator can avoid electrode passivation and overpotential, which strongly inhibit the efficient activation of substrates in electrolysis. Despite the benefits brought by redox catalysis, establishing the precise nature of substrate activation remains challenging. Herein, we determine that a Co( i ) complex bearing two N , N , N -tridentate ligands acts as a competent redox catalyst for the reduction of benzyl bromide substrates. Kinetic studies combining electroanalytical techniques with multivariable linear-regression analysis were conducted, disclosing an outer-sphere electron-transfer mechanism, which occurs in concert with C–Br bond cleavage. Furthermore, we apply a pattern recognition platform to distinguish between mechanisms in the activation of benzyl bromides, found to be dependent on the ligation state of the cobalt( i ) center and ligand used. 

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2. Indole Nucleophile Triggers Mechanistic Divergence in Ni‐Photoredox N‐Arylation

   https://doi.org/10.1002/chem.202402524  

   Liang, Kevin J; Taylor, Olivia R; López, Angie L; Woo, Russell J; Bahamonde, Ana (December 2024, Chemistry – A European Journal)

   Abstract This study presents a Ni‐photoredox method for indoleN‐arylation, broadening the range of substrates to include indoles with unprotected C3‐positions and base‐sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni‐catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni‐photoredox carbon‐heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre‐coordination of indole renders a more electron‐rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron‐rich aryl bromide substrates. Thus, this work highlights the often‐overlooked influence of X‐type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni‐photoredox C‐heteroatom couplings. 

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3. Re-exploring Molecular Complexity with ALMA: Insights into chemical differentiation from the molecular composition of hot cores in Sgr B2(N2)

   https://doi.org/10.1051/0004-6361/202554411  

   Belloche, A; Garrod, R T; Müller, H_S P; Morin, N J; Willis, S A; Menten, K M (June 2025, Astronomy & Astrophysics)

   Context. Hot molecular cores correspond to the phase of star formation during which many molecules, in particular complex organic molecules (COMs), thermally desorb from the surface of dust grains. Sophisticated kinetic models of interstellar chemistry describe the processes that lead to the formation and subsequent evolution of COMs in star-forming regions. Aims. Our goal is to derive the chemical composition of hot cores in order to improve our understanding of interstellar chemistry. In particular, we want to test the models by comparing their predictions to the observed composition of the gas phase of hot cores. Methods. We used the Atacama Large Millimeter/submillimeter Array (ALMA) to perform an imaging spectral line survey of the high mass star-forming region Sagittarius B2(N) at 3 mm, called Re-exploring Molecular Complexity with ALMA (ReMoCA). We modeled under the assumption of local thermodynamic equilibrium the spectra obtained with this survey toward the sources embedded in the secondary hot core Sgr B2(N2). We compared the chemical composition of these sources to that of sources from the literature and to predictions of the chemical kinetics model MAGICKAL. Results. We detected up to 58 molecules toward Sgr B2(N2)’s hot cores, including up to 24 COMs, as well as many less abundant isotopologs. The compositions of some pairs of sources are well correlated, but differences also exist, in particular for HNCO and NH₂CHO. The abundances of series of homologous molecules drop by about one order of magnitude at each further step in complexity. The nondetection of radicals yields stringent constraints on the models. The comparison to the chemical models confirms previous evidence of a high cosmic-ray ionization rate in Sgr B2(N). The comparison to sources from the literature gives a new insight into chemical differentiation. The composition of most hot cores of Sgr B2(N2) is tightly correlated to that of the hot core G31.41+0.31 and the hot corino IRAS 16293–2422 B after normalizing the abundances by classes of molecules (O-bearing, N-bearing, O+N-bearing, and S-bearing). There is no overall correlation between Sgr B2(N2) and the shocked region G+0.693−0.027 also located in Sgr B2, and even less with the cold starless core TMC-1. The class of N-bearing species reveals the largest variance among the four classes of molecules. The S-bearing class shows in contrast the smallest variance. Conclusions. These results imply that the class of N-bearing molecules reacts more sensitively to shocks, low-temperature gas phase chemistry after nonthermal desorption, or density. The overall abundance shifts observed between the N-bearing and O-bearing molecules may indicate how violently and completely the ice mantles are desorbed. 

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4. A preparative small-molecule mimic of liver CYP450 enzymes in the aliphatic C–H oxidation of carbocyclic N -heterocycles

   https://doi.org/10.1073/pnas.2300315120  

   Chambers, Rachel K; Weaver, Jacob D; Kim, Jinho; Hoar, Jason L; Krska, Shane W; White, M Christina (July 2023, Proceedings of the National Academy of Sciences)

   An emerging trend in small-molecule pharmaceuticals, generally composed of nitrogen heterocycles (N-heterocycles), is the incorporation of aliphatic fragments. Derivatization of the aliphatic fragments to improve drug properties or identify metabolites often requires lengthy de novo syntheses. Cytochrome P450 (CYP450) enzymes are capable of direct site- and chemo-selective oxidation of a broad range of substrates but are not preparative. A chemoinformatic analysis underscored limited structural diversity ofN-heterocyclic substrates oxidized using chemical methods relative to pharmaceutical chemical space. Here, we describe a preparative chemical method for direct aliphatic oxidation that tolerates a wide range of nitrogen functionality (chemoselective) and matches the site of oxidation (site-selective) of liver CYP450 enzymes. Commercial small-molecule catalyst Mn(CF₃-PDP) selectively effects direct methylene oxidation in compounds bearing 25 distinct heterocycles including 14 out of 27 of the most frequentN-heterocycles found in U.S. Food and Drug Administration (FDA)-approved drugs. Mn(CF₃-PDP) oxidations of carbocyclic bioisostere drug candidates (for example, HCV NS5B and COX-2 inhibitors including valdecoxib and celecoxib derivatives) and precursors of antipsychotic drugs blonanserin, buspirone, and tiospirone and the fungicide penconazole are demonstrated to match the major site of aliphatic metabolism obtained with liver microsomes. Oxidations are demonstrated at low Mn(CF₃-PDP) loadings (2.5 to 5 mol%) on gram scales of substrate to furnish preparative amounts of oxidized products. A chemoinformatic analysis supports that Mn(CF₃-PDP) significantly expands the pharmaceutical chemical space accessible to small-molecule C–H oxidation catalysis. 

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5. Ruthenium Complexes with Protic Ligands: Influence of the Position of OH Groups and π Expansion on Luminescence and Photocytotoxicity

   https://doi.org/10.3390/ijms24065980  

   Oladipupo, Olaitan E.; Prescott, Meredith C.; Blevins, Emily R.; Gray, Jessica L.; Cameron, Colin G.; Qu, Fengrui; Ward, Nicholas A.; Pierce, Abigail L.; Collinson, Elizabeth R.; Hall, James Fletcher; et al (March 2023, International Journal of Molecular Sciences)

   Protic ruthenium complexes using the dihydroxybipyridine (dhbp) ligand combined with a spectator ligand (N,N = bpy, phen, dop, Bphen) have been studied for their potential activity vs. cancer cells and their photophysical luminescent properties. These complexes vary in the extent of π expansion and the use of proximal (6,6′-dhbp) or distal (4,4′-dhbp) hydroxy groups. Eight complexes are studied herein as the acidic (OH bearing) form, [(N,N)2Ru(n,n′-dhbp)]Cl2, or as the doubly deprotonated (O− bearing) form. Thus, the presence of these two protonation states gives 16 complexes that have been isolated and studied. Complex 7A, [(dop)2Ru(4,4′-dhbp)]Cl2, has been recently synthesized and characterized spectroscopically and by X-ray crystallography. The deprotonated forms of three complexes are also reported herein for the first time. The other complexes studied have been synthesized previously. Three complexes are light-activated and exhibit photocytotoxicity. The log(Do/w) values of the complexes are used herein to correlate photocytotoxicity with improved cellular uptake. For Ru complexes 1–4 bearing the 6,6′-dhbp ligand, photoluminescence studies (all in deaerated acetonitrile) have revealed that steric strain leads to photodissociation which tends to reduce photoluminescent lifetimes and quantum yields in both protonation states. For Ru complexes 5–8 bearing the 4,4′-dhbp ligand, the deprotonated Ru complexes (5B–8B) have low photoluminescent lifetimes and quantum yields due to quenching that is proposed to involve the 3LLCT excited state and charge transfer from the [O2-bpy]2− ligand to the N,N spectator ligand. The protonated OH bearing 4,4′-dhbp Ru complexes (5A–8A) have long luminescence lifetimes which increase with increasing π expansion on the N,N spectator ligand. The Bphen complex, 8A, has the longest lifetime of the series at 3.45 μs and a photoluminescence quantum yield of 18.7%. This Ru complex also exhibits the best photocytotoxicity of the series. A long luminescence lifetime is correlated with greater singlet oxygen quantum yields because the triplet excited state is presumably long-lived enough to interact with 3O2 to yield 1O2. 

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