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1. Tritium hydrogen‐isotope exchange with electron‐poor tertiary benzenesulfonamide moiety; application in late‐stage labeling of T0901317

   https://doi.org/10.1002/jlcr.3958  

   Yongsong, Tian ; Brož, Břetislav ; Tureček, František ; Marek, Aleš ( January 2022 , Journal of Labelled Compounds and Radiopharmaceuticals)

   The multifunctional radioligand [³H]T0901317 ([³H]1) has been employed as a powerful autoradiographic tool to target several receptors, such as liver X, farnesoid X, and retinoic acid‐related orphan receptor alpha and gamma subtypes at nanomolar concentrations. Although [³H]1is commercially available and its synthesis via tritiodebromination has been reported, the market price of this radioligand and the laborious synthesis of corresponding bromo‐intermediate potentially preclude its widespread use in biochemical, pharmacological, and pathological studies in research lab settings. We exploit recent reports on hydrogen‐isotope exchange (HIE) reactions in tertiary benzenesulfonamides where the sulfonamide represents anortho‐directing group that facilitates CH activation in the presence of homogenous iridium(I) catalysts. Herein, we report a time‐ and cost‐efficient method for the tritium late‐stage labeling of compound1—a remarkably electron‐poor substrate owing to the tertiary trifluoroethylsulfonamide moiety. Under a straightforward HIE condition using a commercially available Kerr‐type NHC Ir(I) complex, [(cod)Ir (NHC)Cl], the reaction with1afforded a specific activity of 10.8 Ci/mmol. Additionally, alternative HIE conditions using the heterogeneous catalyst of Ir‐black provided sufficient 0.72 D‐enrichment of1but unexpectedly failed while repeating with tritium gas.

    

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2. Nuclear Spin Hyperpolarization of NH 2 ‐ and CH 3 ‐Substituted Pyridine and Pyrimidine Moieties by SABRE

   https://doi.org/10.1002/cphc.202000483  

   Mandal, Ratnamala ; Pham, Pierce ; Hilty, Christian ( September 2020 , ChemPhysChem)

   Hyperpolarization of N‐heterocycles with signal amplification by reversible exchange (SABRE) induces NMR sensitivity gains for biological molecules. Substitutions with functional groups, in particular in theortho‐position of the heterocycle, however, result in low polarization using a typical Ir catalyst with a bis‐mesityl N‐heterocyclic carbene ligand for SABRE, presumably due to steric hindrance. With the addition of allylamine or acetonitrile as coligands to the precatalyst chloro(1,5‐cyclooctadiene)[4,5‐dimethyl‐1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene] iridium, the¹H signal enhancement increased in several substrates withorthoNH₂substitutions. For example, for a proton in 2,4‐diaminopyrimidine, the enhancement factors increased from −7±1 to −210±20 with allylamine or to −160±10 with acetonitrile. CH₃substituted molecules yielded maximum signal enhancements of −25±7 with acetonitrile addition, which is considerably less than the corresponding NH₂substituted molecules, despite exhibiting similar steric size. With the more electron‐donating NH₂substitution resulting in greater enhancement, it is concluded that steric hindrance is not the only dominant factor in determining the polarizability of the CH₃substituted compounds. The addition of allylamine increased the signal enhancement for the 290 Da trimethoprim, a molecule with a 2,4‐diaminopyrimidine moiety serving as an antibacterial agent, to −70.

    

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3. Selective deuteration as a tool for resolving autoxidation mechanisms in α -pinene ozonolysis

   https://doi.org/10.5194/acp-23-4373-2023  

   Meder, Melissa ; Peräkylä, Otso ; Varelas, Jonathan G. ; Luo, Jingyi ; Cai, Runlong ; Zhang, Yanjun ; Kurtén, Theo ; Riva, Matthieu ; Rissanen, Matti ; Geiger, Franz M. ; et al ( January 2023 , Atmospheric Chemistry and Physics)

   Abstract. Highly oxygenated organic molecules (HOMs) from α-pinene ozonolysis have been shown to be significant contributors to secondary organic aerosol (SOA), yet our mechanistic understanding of how the peroxy-radical-driven autoxidation leads to their formation in this system is still limited. The involved isomerisation reactions such as H-atom abstractions followed by O2 additions can take place on sub-second timescales in short-lived intermediates, making the process challenging to study. Similarly, while the end-products and sometimes radical intermediates can be observed using mass spectrometry, their structures remain elusive. Therefore, we propose a method utilising selective deuterations for unveiling the mechanisms of autoxidation, where the HOM products can be used to infer which C atoms have taken part in the isomerisation reactions. This relies on the fact that if a C−D bond is broken due to an abstraction by a peroxy group forming a −OOD hydroperoxide, the D atom will become labile and able to be exchanged with a hydrogen atom in water vapour (H2O), effectively leading to loss of the D atom from the molecule. In this study, we test the applicability of this method using three differently deuterated versions of α-pinene with the newly developed chemical ionisation Orbitrap (CI-Orbitrap) mass spectrometer to inspect the oxidation products. The high mass-resolving power of the Orbitrap is critical, as it allows the unambiguous separation of molecules with a D atom (mD=2.0141) from those with two H atoms (mH2=2.0157). We found that the method worked well, and we could deduce that two of the three tested compounds had lost D atoms during oxidation, suggesting that those deuterated positions were actively involved in the autoxidation process. Surprisingly, the deuterations were not observed to decrease HOM molar yields, as would have been expected due to kinetic isotope effects. This may be an indication that the relevant H (or D) abstractions were fast enough that no competing pathways were of relevance despite slower abstraction rates of the D atom. We show that selective deuteration can be a very useful method for studying autoxidation on a molecular level and likely is not limited to the system of α-pinene ozonolysis tested here.

    

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4. Effects of a Tridentate Pincer Ligand on Parahydrogen Induced Polarization

   https://doi.org/10.1002/cphc.202100178  

   Muhammad, Safiyah R. ; Nugent, Joseph W. ; Greer, Rianna B. ; Lee, Brian C. ; Mahmoud, Jumanah ; Ramirez, Steven B. ; Goodson, Boyd. M. ; Fout, Alison R. ( June 2021 , ChemPhysChem)

   The role of ligands in rhodium‐ and iridium‐catalyzedParahydrogen Induced Polarization (PHIP) and SABRE (signal amplification by reversible exchange) chemistry has been studied in the benchmark systems, [Rh(diene)(diphos)]⁺and [Ir(NHC)(sub)₃(H)₂]⁺, and shown to have a great impact on the degree of hyperpolarization observed. Here, we examine the role of the flanking moieties in the electron‐rich monoanionic bis(carbene) aryl pincer ligand,^ArCCC (Ar=Dipp, 2,6‐diisopropyl or Mes, 2,4,6‐trimethylphenyl) on the cobalt‐catalyzed PHIP and PHIP‐IE (PHIP via Insertion and Elimination) chemistry that we have previously reported. The mesityl groups were exchanged for diisopropylphenyl groups to generate the (^DippCCC)Co(N₂) catalyst, which resulted in faster hydrogenation and up to 390‐fold¹H signal enhancements, larger than that of the (^MesCCC)Co‐py (py=pyridine) catalyst. Additionally, the synthesis of the (^DippCCC)Rh(N₂) complex is reported and applied towards the hydrogenation of ethyl acrylate withparahydrogen to generate modest signal enhancements of both¹H and¹³C nuclei. Lastly, the generation of two (^MesCCC)Ir complexes is presented and applied towards SABRE and PHIP‐IE chemistry to only yield small¹H signal enhancements of the partially hydrogenated product (PHIP) with no SABRE hyperpolarization.

    

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5. Crystal structures of three copper(II)–2,2′-bipyridine (bpy) compounds, [Cu(bpy) 2 (H 2 O)][SiF 6 ]·4H 2 O, [Cu(bpy) 2 (TaF 6 ) 2 ] and [Cu(bpy) 3 ][TaF 6 ] 2 and a related coordination polymer, [Cu(bpy)(H 2 O) 2 SnF 6 ] n

   https://doi.org/10.1107/S2056989021000633  

   Nisbet, Matthew L. ; Hiralal, Emily ; Poeppelmeier, Kenneth R. ( February 2021 , Acta Crystallographica Section E Crystallographic Communications)

   null (Ed.)

   We report the hydrothermal syntheses and crystal structures of aquabis(2,2′-bipyridine-κ 2 N , N ′)copper(II) hexafluoridosilicate tetrahydrate, [Cu(bpy) 2 (H 2 O)][SiF 6 ]·4H 2 O (bpy is 2,2′-bipyridine, C 10 H 8 N 2 ), (I), bis(2,2′-bipyridine-3κ 2 N , N ′)-di-μ-fluorido-1:3κ 2 F : F ;2:3κ 2 F : F -decafluorido-1κ 5 F ,2κ 5 F -ditantalum(V)copper(II), [Cu(bpy) 2 (TaF 6 ) 2 ], (II), tris(2,2′-bipyridine-κ 2 N , N ′)copper(II) bis[hexafluoridotantalate(V)], [Cu(bpy) 3 ][TaF 6 ] 2 , (III), and catena -poly[[diaqua(2,2′-bipyridine-κ 2 N , N ′)copper(II)]-μ-fluorido-tetrafluoridotin-μ-fluorido], [Cu(bpy)(H 2 O) 2 SnF 6 ] n , (IV). Compounds (I), (II) and (III) contain locally chiral copper coordination complexes with C 2 , D 2 , and D 3 symmetry, respectively. The extended structures of (I) and (IV) are consolidated by O—H...F and O—H...O hydrogen bonds. The structure of (III) was found to be a merohedral (racemic) twin. 

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