Influence of the COVID-19 pandemic on causes for the development of carbon monoxide intoxications.

Introduction: Several causes can lead to carbon monoxide (CO) intoxication. A first-line treatment option for such intoxications is hyperbaric oxygenation (HBO2) therapy. The COVID-19 pandemic has been changing everyday life in Germany since March 2020, mainly caused by statutory provisions. Our aim was to review whether these changes have an influence on the causes and frequency for the development of CO intoxication. Methods: We retrospectively analyzed the data of patients who were treated for CO intoxication in our institution between April 2019 and March 2021. Besides demographic data, we compared the overall number and documented causes for each CO intoxication in the period of April 2020 to March 2021 with the period between April 2019 and March 2020. Results: After applying inclusion and exclusion criteria, 139 patients were included. We found a significant decrease in the overall number of patients who needed treatment since the beginning of the COVID-19 pandemic. However, the share of CO intoxication caused by the indoor use of coal stoves, coal barbecue, or suicide attempts increased. In contrast, the share of cases caused by apartment or house fire, smoking waterpipe, or gas stoves decreased. Conclusion: The COVID-19 pandemic and the associated restrictions lead to a significant reduction in the number of patients in need for HBO2 therapy due to CO-Intoxication. The causes leading to CO intoxication also changed since the beginning of the COVID-19 pandemic. We observed a shift toward causes related to the indoor use of coal-fired stoves and barbecues as well as suicide attempts.

Ethanol(nitrato)[tris-(4-cyano-3-phenyl-1H-pyrazol-1-yl)hydroborato]nickel(II).

The synthesis and structure is reported of TpPh,4CNNi(NO3)(EtOH) or [Ni(C30H19BN9)(NO3)(C2H6O)], the first half-sandwich complex of a cyano-scorpionate ligand. The pseudo-octa-hedral coordination sphere of the NiII ion is comprised of a tridentate tris-(4-cyano-3-phenyl-pyrazol-yl)borate ligand, a bidentate nitrate ligand and a neutral ethanol ligand. The phenyl substituents on the TpPh,4CN ligand are relatively parallel to the planes of the ethanol and nitrate ligands. An inter-molecular hydrogen-bonding inter-action is evident between the ethanol OH group and the pyrazole CN substituent. The ethanol ligand was modeled with a 0.572 (13)/0.428 (13) disorder of the methyl C atom.

Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases.

1,2-Benzisothiazol-3(2H)-ones and 1,3,4-oxadiazoles individually have recently attracted considerable interest in drug discovery, including as antibacterial and antifungal agents. In this study, a series of functionalized 1,2-benzisothiazol-3(2H)-one-1,3,4-oxadiazole hybrid derivatives were synthesized and subsequently screened against Dengue and West Nile virus proteases. Ten out of twenty-four compounds showed greater than 50% inhibition against DENV2 and WNV proteases ([I] = 10 µM). The IC(50) values of compound 7n against DENV2 and WNV NS2B/NS3 were found to be 3.75 ± 0.06 and 4.22 ± 0.07 µM, respectively. The kinetics data support a competitive mode of inhibition by compound 7n. Molecular modeling studies were performed to delineate the putative binding mode of this series of compounds. This study reveals that the hybrid series arising from the linking of the two scaffolds provides a suitable platform for conducting a hit-to-lead optimization campaign via iterative structure-activity relationship studies, in vitro screening and X-ray crystallography.

A linear S-bridged trinuclear cobalt(III) complex with 2-aminobenzenethiol: Synthesis, crystal structure, and spectroscopic characterization.

Treatment of cobalt(II) perchlorate hexahydrate with 2 molar equiv. of 2-aminobenzenethiol (Habt) in acetonitrile afforded a tricationic tricobalt complex, [Co{Co(abt)3}2](ClO4)3·2CH3CN, by aerial oxidation. The molecular structure of the meso (ΔΛ) form of the complex was determined by X-ray crystallography. In the complex cation, the central Co is coordinated by six thiolate groups from two terminal fac(S)-[Co(abt)3] units in an octahedral geometry, forming a linear S-bridged tricobalt structure.

Tridentate N(2)S ligand from 2,2'-dithiodibenzaldehyde and N,N-dimethylethylenediamine: Synthesis, structure, and characterization of a Ni(II) complex with relevance to Ni Superoxide Dismutase.

Nickel Superoxide Dismutase (NiSOD) and the A-cluster of Carbon Monoxide Dehydrogenase/Acetyl Coenzyme A Synthase (CODH/ACS) both feature active sites with Ni coordinated by thiolate and amide donors. It is likely that the particular set of donors is important in tuning the redox potential of the Ni center(s). We report herein an expansion of our efforts involving the use of 2,2'-dithiodibenzaldehyde (DTDB) as a synthon for metal-thiolate complexes to reactions with Ni complexes of N,N-dimethylethylenediamine (dmen). In the presence of coordinating counterions, these reactions result in monomeric square-planar complexes of the tridentate N(2)S donor ligand derived from the Schiff-base condensation of dmen and DTDB. In the absence of a coordinating counterion, we have isolated a Ni(II) complex with an asymmetric N(2)S(2) donor set involving one amine and one imine N donor in addition to two thiolate donors. This latter complex is discussed with respect to its relevance to the active site of NiSOD.

Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3.

The S' subsites of human neutrophil proteinase 3 (Pr 3) were probed by constructing diverse libraries of compounds based on the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide using combinational and click chemistry methods. The multiple points of diversity embodied in the heterocyclic scaffold render it well-suited to the exploration of the S' subsites of Pr 3. Molecular modeling studies suggest that further exploration of the S' subsites of Pr 3 using the aforementioned heterocyclic scaffold may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3.

2-Fluoro-l-histidine.

The title compound, C(6)H(8)FN(3)O(2), an analog of histidine, shows a reduced side-chain pK(a) (ca 1). The title structure exhibits a shortening of the bond between the proximal ring N atom and the F-substituted ring C atom, indicating an increase in π-bond character due to an inductive effect of fluorine.

Two similar dibenzo cyclic ethers with dissimilar conformations.

Two dibenzo cyclic ether compounds, 6,12-dibromodibenzo[d,i]-1,2,3,6,7,8-hexahydro-1,3-dioxecin (systematic name: 8,16-dibromo-2,4-dioxatricyclo[12.4.0.0(5,10)]octadeca-5,7,9,14,16,18-hexaene), C(16)H(14)Br(2)O(2), (II), and 8,14-dibromodibenzo[f,k]-1,5-dioxa-1,2,3,4,5,8,9,10-octahydrocyclododecene (systematic name: 7,19-dibromo-11,15-dioxatricyclo[14.4.0.0(5,10)]icosa-5,7,9,16,18,20-hexaene), C(18)H(18)Br(2)O(2), (III), were prepared as scaffolding for phosphate-anion receptors. In both compounds, the two aromatic rings are linked by three methylene units ortho to the oxygen substituent of each ring. The only difference between the two compounds is the number of methylene units linking the two ether O atoms. The dibenzo cyclic ether with an ether linkage of one methylene unit adopts a chair-like conformation, where the two aromatic rings are parallel to each other. On the other hand, the dibenzo cyclic ether with an oxygen linkage of three methylene units adopts a bowl-like conformation. The latter scaffold configuration is the only structure of the two that would allow for the placement of convergent functional groups necessary for the establishment of an anion-selective binding pocket.

Iron and Cobalt Complexes of 2,6-Diacetylpyridine-bis(R-thiosemicarbazone) (R=H, phenyl) Showing Unprecedented Ligand Deviation from Planarity.

The syntheses, characterization, and single-crystal X-ray crystal structures are reported for four complexes of iron and cobalt with the pentadentate ligands, 2,6-diacetylpyridinebis(thiosemicarbazone) (H(2)L(1)) and 2,6-diacetylpyridinebis-(phenylthiosemicarbazone) (H(2)L(2)), including a cobalt dimer displaying a deviation from planarity which is unprecedented for this class of ligands and allows the ligand to occupy five positions of a pseudo-octahedral coordination sphere. This dimer reacts with KCN to produce a mononuclear complex of relevance to the active site of cobalt nitrile hydratase.

Cyanoscorpionates: synthesis and crystallographic characterization of one-dimensional Cu(I) coordination polymers.

A new cyanoscorpionate ligand, hydrotris(3- t-butyl-4-cyanopyrazolyl)borate (Tp ( t-Bu,4CN )) is reported. Both Tp ( t-Bu,4CN ) and hydrotris(4-cyano-3-phenylpyrazolyl)borate (Tp (Ph,4CN)) form one-dimensional coordination polymers with Cu(I). The polymeric chains align to form channels which, in the case of Tp ( t-Bu,4CN ), can encapsulate solvent molecules, as evidenced by the characterization of one such polymer with encapsulated acetonitrile molecules.

Sandwich compounds of cyanotrispyrazolylborates: complexation-induced ligand isomerization.

Reaction of the new cyanoscorpionate ligand, hydrotris(4-cyano-3-phenyl)pyrazolylborate (Tp(Ph),(4CN)) with Co(II), Mn(II), and Fe(II) unexpectedly results in the isolation only of crystals containing sandwich complexes in which the ligands have been isomerized to produce the heterocyanoscorpionate hydrobis(4-cyano-3-phenylpyrazolyl)(4-cyano-5-phenylpyrazolyl)borate (Tp(Ph),(4CN*)). The three complexes have been characterized crystallographically and are isostructural, with each ligand acting in a tridentate manner toward the metal. The isomerization of the ligand appears to be more facile than that of the analogous non-cyano ligand, Tp(Ph), with which crystals of the unisomerized sandwich compound have been isolated for Mn(II) and Fe(II).

Incorporation of thiolate donation using 2,2'-dithiodibenzaldehyde: complexes of a pentadentate N2S3 ligand with relevance to the active site of Co nitrile hydratase.

The use of 2,2'-dithiodibenzaldehyde (DTDB) as a reactant for incorporating thiolate donors into the coordination sphere of a transition metal complex without the need for protecting groups is expanded to include the synthesis of complexes with pentadentate ligands. The ligand N,N'-bis(thiosalicylideneimine)-2,2'-thiobis(ethylamine) (tsaltp) is synthesized at a cobalt center by the reaction of DTDB with a Co complex of thiobis(ethylamine). The resulting Co complexes are thus coordinated by the N(2)S(3) pentadentate ligand through two imine N atoms, two thiolate S atoms, and one thioether S atom. A dimeric, bis-thiolate-bridged complex (1) is isolated and converted to a monomeric CN adduct (2) by treatment with KCN. The N(2)S(3) coordination environment provided by the tsaltp ligand is similar to that provided by the protein donors at the active site of the nitrile hydratase enzymes, with 2 being the first octahedral Co complex reported with such a coordination sphere.

Serendipitous discovery of an unexpected rearrangement leads to two new classes of potential protease inhibitors.

The pathogenesis of a range of human diseases arises from the aberrant activity of proteolytic enzymes. Agents capable of selectively modulating the activity of these enzymes are of potential therapeutic value. Thus, there is a continuing need for the design of scaffolds that can be used in the development of new classes of protease inhibitors. We describe herein the serendipitous discovery of an unexpected rearrangement that leads to the formation of two novel templates that can be used in the design of protease inhibitors.

Direct observation of fine structure transitions in a paramagnetic nickel(II) complex using far-infrared magnetic spectroscopy: a new method for studying high-spin transition metal complexes.

Novel far-infrared (FIR) absorption spectroscopy in conjunction with multiple, fixed external magnetic fields (FIR magnetic spectroscopy, FIRMS) has been used to investigate pseudotetrahedral complexes with the formula M(PPh(3))(2)Cl(2) (M = Ni, Zn; Ph = C(6)H(5)). Crystal structures have been reported for the Ni complex; we report the structure of the Zn complex. Transmission spectra at 5 K of Ni(PPh(3))(2)Cl(2) (S = 1) at zero magnetic field exhibit absorption bands at 11.41, 15.28, and 23.0 cm(-1). The two lower frequency bands show great sensitivity to external magnetic field, and their field dependence is as expected for electron spin transitions allowing precise determination of the following parameters: |D| = 13.35(1) cm(-1), |E| = 1.93(1) cm(-1), g(x,y) = 2.20(1), g(z) = 2.00(1). Corresponding spectra of Zn(PPh(3))(2)Cl(2) (S = 0) exhibit bands only at >20 cm(-1), which show no field dependence. FIRMS is a promising technique for direct investigation of the electronic structure of high-spin transition metal complexes.

Pulsed ENDOR and ESEEM Study of [Bis(maleonitriledithiolato)nickel](-): An Investigation into the Ligand Electronic Structure.

By a combination of Q-band pulsed ENDOR (electron nuclear double resonance) and X-band ESEEM (electron stimulated echo envelope modulation) techniques, we have determined the hyperfine tensors for ethylene (C1) and cyano (C2) carbons and N, of [Ni(mnt)(2)](-), along with the quadrupole tensor for nitrogen. These measurements give pi electron spin densities of rho(C1) approximately 0.03 in the C1 2p(z)() orbital, rho(C2) < 0.003, rho(N) approximately 0.01, such that in total, approximately 0.15 of the spin resides on the ligand atoms C and N, while the rest resides in the NiS(4) core, giving rho(NiS(4)(-)) = 0.85. These results are compared with extended Hückel and density functional (BLYP) MO calculations, as well as with Xalpha calculations reported earlier.