Synthesis,Characterization, and X-Ray Structures of 2-(3,5-Dimethylpyrazol-1-Yl)Phenyl-Based Organoselenium Compounds and Their Glutathione Peroxidase (Gpx) Like Activity

Abstract

The synthesis of a series of 2-(3,5-dimethylpyrazol-1-yl)phenyl-based organoselenium compounds, (dmpzC₆H₄Se)₂ (1), dmpzC₆H₄SeR (dmpz = 3,5-dimethylpyrazol-1-yl; R = (CH₂)_nY; Y = OH, NH₂, and COOH), and dmpzC₆H₄SeX (X = Cl, Br, or I) is described. The compounds are characterized by IR, NMR (¹H, ¹³C{¹H}, ⁷⁷Se{¹H}), and mass spectral (MS) data. The molecular structures of (dmpzC₆H₄Se)₂, dmpzC₆H₄SeCH₂COOH, and dmpzC₆H₄SeCH₂CH₂OH have been established by X-ray crystallography. The two latter compounds are associated in the solid state through intermolecular hydrogen bonding between the OH proton and the pyrazolyl nitrogen atom of the adjacent molecule. Glutathione peroxidase (GPx) like catalytic activity of these compounds has been evaluated by using hydrogen peroxide (H₂O₂) as substrate and dithiothreitol (DTT^red) as thiol cofactor in CD₃OD, and the progress of the reaction was monitored by ¹H NMR spectroscopy. All the compounds exhibited the GPx-like catalytic activity. Among these, the ones containing alkylamino groups showed the best activity.

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Optically active phosphine oxides: 10 [1]; X-ray structure and conformation of (Sp)- and (Rp)-L-menthyl α-(phenylvinylphosphinyl)acetates

The structures and solid-state stereochemistry of the two P-epimeric compounds ( 1 and 2 ) formed in a reaction of butyl phenylvinylphosphinite with (-)-L-menthyl bromoacetate were studied by X-ray crystallography and CP–MAS ¹³C NMR spectroscopy. The two compounds were also analyzed in solution by means of 2D ¹H NMR, ¹³C NMR, IR, UV, and dipole moment measurement techniques. Compound 1 , C₂₀H₂₉O₃P, crystallized in the orthorhombic group P 2₁2₁2₁ with Z = 4, a = 20.491(2), b = 16.719(1), and c = 5.910(1). Compound 2 , C₂₀H₂₉O₃P, crystallized in the monoclinic space group P 2₁ with Z = 2, a = 9.266(1), b = 9.852(1), c = 10.954(1), and β = 95.20(1)°. In the crystals both compounds possess their CC PO fragments in an s-cis array, and have their PO and CO dipoles oriented uniformly in a syn, nearly parallel, fashion. In solution, however, an anti arrangement of these two dipoles is slightly preferred.     

FT‐IR Study of Some Carotenoids

Some natural and semisynthetic carotenoids were examined by means of FT‐IR spectroscopy. The IR bands of the characteristic functional groups (CH₃, CH₂, CC, CO, OH, etc.) were assigned when possible. Some special functional groups – without H‐atoms – such as CCC, ‘cross epoxides', etc., which cannot be easily identified by ¹H‐NMR methods, were also detected in the FT‐IR spectra.     

Selenate—An internal chemical shift standard for aqueous 77Se NMR spectroscopy

The ⁷⁷Se NMR spectra of selenate were studied under various circumstances, such as concentration, pH, temperature, ionic strength, and D₂O:H₂O ratio, in order to examine its potential as a water-soluble internal chemical shift standard. The performance of selenate as a chemical shift reference and that of other attempted ones from the literature (dimethyl selenide, tetramethylsilane/TMS, and 3-(trimethylsilyl)propane-1-sulfonate/DSS) was also explored. The uncertainty in the resulting chemical shift relative to the effective spectral width is comparable to that of DSS. Compared to the currently prevalent water-soluble external chemical shift reference, selenic acid solution, the properties of internal selenate are much more favorable in terms of ease of use. We have also demonstrated that selenate can be used in reducing media, which is inevitable for the analysis of selenol compounds. Thus, it can be stated that sodium selenate is a robust internal chemical shift reference in aqueous media for ⁷⁷Se NMR measurements; the chemical shift of this reference in a solution containing 5 V/V% D₂O at 25°C and 0.15 mol·dm⁻³ ionic strength is 1048.65 ppm relative to 60 V/V% dimethyl selenide in CDCl₃ and 1046.40 ppm relative to the ¹H signal of 0.03 V/V% TMS in CDCl₃. In summary, a water-soluble, selenium-containing internal chemical shift reference compound was introduced for ⁷⁷Se NMR measurements for the first time in the literature, and with the aforementioned results all previous ⁷⁷Se measurements can be converted to a unified scale defined by the International Union of Pure and Applied Chemistry.     

Galectin–Glycan Interactions: Guidelines for Monitoring by 77Se NMR Spectroscopy,and Solvent (H2O/D2O) Impact on Binding

Functional pairing between cellular glycoconjugates and tissue lectins like galectins has wide (patho)physiological significance. Their study is facilitated by nonhydrolysable derivatives of the natural O-glycans, such as S- and Se-glycosides. The latter enable extensive analyses by specific ⁷⁷Se NMR spectroscopy, but still remain underexplored. By using the example of selenodigalactoside (SeDG) and the human galectin-1 and -3, we have evaluated diverse ⁷⁷Se NMR detection methods and propose selective ¹H,⁷⁷Se heteronuclear Hartmann–Hahn transfer for efficient use in competitive NMR screening against a selenoglycoside spy ligand. By fluorescence anisotropy, circular dichroism, and isothermal titration calorimetry (ITC), we show that the affinity and thermodynamics of SeDG binding by galectins are similar to thiodigalactoside (TDG) and N-acetyllactosamine (LacNAc), confirming that Se substitution has no major impact. ITC data in D₂O versus H₂O are similar for TDG and LacNAc binding by both galectins, but a solvent effect, indicating solvent rearrangement at the binding site, is hinted at for SeDG and clearly observed for LacNAc dimers with extended chain length.     

Multinuclear NMR studies on CF3 substituted sulfur,selenium and tellurium compounds

A systematic investigation of thirty-four CF₃Se(II, IV) and eight CF₃Te(II, IV) compounds by ¹³C, ¹⁹F, ⁷⁷Se and ¹²⁵Te NMR spectroscopy resulted in some general features for chemical shifts and coupling constants which agree with the trends of reported ¹⁹F and new ¹³C NMR data of CF₃S(II, IV) compounds. Moreover, the NMR spectra of molecules of the type E=CXY (E = chalcogen, X, Y = halogen) and substances containing a CSe double bond have been studied. From the comparison of these NMR data with those of CF₃ substituted chalcogen compounds, a partial double bond character of the carbon-fluorine and carbon-chalcogen bond in CF₃ substituted chalcogen compounds can be derived:

     

Synthesis,Characterization, and Structures of α-Substituted Selenenyl-Acetophenones

Abstract

A series of α-substituted selenenyl acetophenone derivatives of the types, [PhC(OCH₂CH₂O)CH₂Se]₂, [PhC(OCH₂CH₂O)CH₂SeR], (PhCOCH₂Se)_2, and [PhCOCH₂SeR] have been prepared. These compounds have been characterized by elemental analyses, IR and NMR (¹H, ¹³C, ⁷⁷Se) spectroscopy. The compounds, [PhC(OCH₂CH₂)CH₂Se]₂ and (PhCOCH₂Se)₂ have been structurally characterized by single crystal X-ray diffraction analyses. The former shows intra-molecular Se‐?‐?‐O interaction, while the latter exhibits inter-molecular nonbonding Se‐?‐?‐O interaction.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Physical- and Bio-Organic Chemstry of Nonbonded Selenium· · ·Oxygen Interactions

Weak nonbonded interaction between a divalent selenium and an oxygen atom (i.e., Se···O interaction) frequently plays important roles in chemical and biological functions of selenium compounds. To establish that ⁷⁷ Se NMR is an easy experimental probe to diagnose the strength of an Se···O interaction, 3 series of 2-substituted benzeneselenenyl derivatives, which have an intramolecular Se···O interaction in solution, were employed. By comparing the ⁷⁷ Se NMR chemical shifts (δ _Se ) with those observed for other series of selenium compounds, which have an intramolecular Se···Y (Y = N, O, F, Cl, or Br) interaction, approximate linear correlation was found between the δ _Se values and the strengths of the nonbonded Se···Y interactions evaluated by natural bond orbital analysis at the B3LYP level. The correlation will be useful for estimating the strength of an Se···O interaction simply from the ⁷⁷ Se NMR chemical shift. By extending the chemistry of nonbonded Se···O interactions to structural biology, analogous S···O interactions have been discovered in protein architecture. The directional features were, however, different from those of Se···O and S···O interactions of small organic compounds.     

Synthesis and Characterization of trans‐PdII Trimethylsilylchalcogenolates

The trans‐bis(trimethylsilyl)chalcogenolate palladium complexes, trans‐[Pd(ESiMe₃)₂(PnBu₃)₂] [E = S ( 1 ) and Se ( 2 )] were synthesized in good yields and high purity by reacting trans‐[PdCl₂(PBu₃)₂] with LiESiMe₃ (E = S, Se), respectively. These complexes were characterized by ¹H, ¹³C{¹H}, ³¹P{¹H} (and ⁷⁷Se{¹H}) NMR spectroscopy and single‐crystal X‐ray analysis. The reaction of 2 with propionyl chloride led to the formation of trans‐[Pd(SeC(O)CH₂CH₃)₂(PnBu₃)₂] ( 3 ), a trans‐bis(selenocarboxylato) palladium complex and thus established a new method for the formation of this type of complex. Complex 3 was characterized by ¹H, ¹³C{¹H}, ³¹P{¹H} and ⁷⁷Se{¹H} NMR spectroscopy and a single‐crystal X‐ray structure analysis.     

Planarity of acetamides,thioacetamides, and selenoacetamides: Crystal structure of N,N‐dimethylselenoacetamide

The planarity of acetamides 1a–3a , thioacetamides 4a–6a , and selenoacetamides 7a–9a , R¹R²NC(=E)CH₃ where E = O, S, Se, and R¹, R² = H or CH₃, was investigated using theoretical calculations at the density functional theory (DFT) level. The calculations showed that the methyl substitution on nitrogen and the change from the amide moiety (NCO) to NCS or NCSe group increased the double bond character of the N C bond. In other words, the planarity of these compounds ( 1a–9a ) increases in the order NH₂ < NHCH₃ < N(CH₃)₂ and O < S < Se. The calculations of bending energy suggest that the planar geometry represents the lowest energy conformation for all compounds investigated in this work. N,N‐Dimethyl‐selenoacetamide ( 9a ), (CH₃)₂NC(Se) CH₃, has the largest bending energy of 10.37 kcal/mol, which suggests that it possesses the greatest planarity among the compounds 1a–9a . However, the solid phase molecular structure of 9a was found to be slightly nonplanar by X‐ray crystallography. The slight nonplanarity observed experimentally is very likely the consequence of intermolecular interactions arising within the crystal packing. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:380–386, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10056     

Sol–gel derived Si/C/O/N‐materials: molecular model compounds,xerogels and porous ceramics

Polymeric Si/C/O/N xerogels, with the idealized polymer network structure comprising [Si O Si(NCN)₃]_n moieties, were prepared by reactions of hexachlorodisiloxane (Cl₃Si O SiCl₃) with bis(trimethylsilyl)carbodiimide (Me₃Si NCN SiMe₃, BTSC). NMR and FTIR spectra indicate the existence of ‐NCN‐ and Si O Si‐ units in the xerogels and also in the ceramic materials obtained upon pyrolysis. The feasibility of this reaction protocol was confirmed on the molecular level by the deliberate synthesis of the macrocyclic compound [SiPh₂ O SiPh₂(NCN)]₂, the crystal structure and spectroscopic data of which are reported. The influence of pyridine as a catalyst for the cross‐linking reaction was studied. The degree of cross‐linking increased within the polymers with the addition of pyridine. It was shown by the reaction of hexachlorodisiloxane with excess pyridine that the latter appears to activate only one out of the two ‐SiCl₃ moieties under formation of hexacoordinated silicon compounds. The crystal structure of Cl₃Si O SiCl₃(pyridine)₂ is presented. Quantum chemical calculations are in support of this adduct being a potential intermediate in the pyridine catalyzed sol–gel process. The ceramic yield after pyrolysis of the Si/C/O/N‐xerogels at 1000 °C, which reaches values up to 50%, was found to depend on the aging protocol (time, temperature), whereas no correlation was found with the amount of pyridine added for xerogel synthesis. The Si/C/N/O‐ceramics obtained after pyrolysis at 1000 °C under NH₃ are completely amorphous. Chemically they have to be considered as hybrids between an ideal [SiOSi(NCN)₃]_n network and glass‐like Si₂N₂O. The products are mesoporous with closed pores and a broad pore size distribution. Copyright © 2011 John Wiley & Sons, Ltd.     

The synthesis of new cyclic thioquinone derivatives

New bis(thio)substituted, S‐,O‐substituted, and S‐,S‐substituted benzoquinone compounds were synthesized from the reaction of p‐chloranil ( 1 ) with S‐,O‐substituted thiols, dithiols, and monothiols. The ¹³C NMR spectra and the IR spectra of heterocyclic compounds 3 , 4 and 7 , 8 showed different behavior; that of 3 , 7 showed a carbon signal and a >CO group band for the carbonyl group and that of 4 , 8 showed two carbon signals and split bands for the carbonyl group. The structures of the novel compounds were characterized by microanalysis, FT‐IR, ¹H NMR, ¹³C NMR, MS, and UV–vis spectroscopy. The crystal structure of 2,3,5,6‐tetrakis(4‐fluorobenzylthio)cyclohexa‐2,5‐diene‐1,4‐dione ( 15 ) was determined by the X‐ray diffraction method. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:446–452, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20634     

Sterically Crowded peri‐Substituted Naphthalene Phosphines and their PV Derivatives

Three sterically crowded peri‐substituted naphthalene phosphines, Nap[PPh₂][ER] (Nap=naphthalene‐1,8‐diyl; ER=SEt, SPh, SePh) 1–3 , which contain phosphorus and chalcogen functional groups at the peri positions have been prepared. Each phosphine reacts to form a complete series of P^V chalcogenides Nap[P(E′)(Ph₂)(ER)] (E′=O, S, Se). The novel compounds were fully characterised by using X‐ray crystallography and multinuclear NMR spectroscopy, IR spectroscopy and MS. X‐ray data for 1 , 2 , n O , n S , n Se (n=1–3) are compared. Eleven molecular structures have been analysed by naphthalene ring torsions, peri‐atom displacement, splay angle magnitude, X???E interactions, aromatic ring orientations and quasi‐linear arrangements. An increase in the congestion of the peri region following the introduction of heavy chalcogen atoms is accompanied by a general increase in naphthalene distortion. P???E distances increase for molecules that contain bulkier atoms at the peri positions and also when larger chalcogen atoms are bound to phosphorus. The chalcogenides adopt similar conformations that contain a quasi‐linear E???P? C fragment, except for 3 O , which displays a twist‐axial‐twist conformation resulting in the formation of a linear O???Se? C alignment. Ab initio MO calculations performed on 2 O , 3 O , 3 S and 3 Se reveal Wiberg bond index values of 0.02 to 0.04, which indicates only minor non‐bonded interactions; however, calculations on radical cations of 3 O , 3 S and 3 Se reveal increased values (0.14–0.19).     

Early Main Group Metal Catalysis: How Important is the Metal?

Organocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal–alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca²⁺. The role of the metal was evaluated by a study using the metal‐free catalysts: [Ph₂N⁻][Me₄N⁺] and [Ph₃C⁻][Me₄N⁺]. These “naked” amides and carbanions can act as catalysts in the conversion of activated double bonds (CO and CN) in the hydroamination of Ar NCO and R NCN R (R=alkyl) by Ph₂NH. For the intramolecular hydroamination of unactivated CC bonds in H₂CCHCH₂CPh₂CH₂NH₂ the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study.     

SEAL by NMR: Glyco‐Based Selenium‐Labeled Affinity Ligands Detected by NMR Spectroscopy

We report a method for the screening of interactions between proteins and selenium‐labeled carbohydrate ligands. SEAL by NMR is demonstrated with selenoglycosides binding to lectins where the selenium nucleus serves as an NMR‐active handle and reports on binding through ⁷⁷Se NMR spectroscopy. In terms of overall sensitivity, this nucleus is comparable to ¹³C NMR, while the NMR spectral width is ten times larger, yielding little overlap in ⁷⁷Se NMR spectroscopy, even for similar compounds. The studied ligands are singly selenated bioisosteres of methyl glycosides for which straightforward preparation methods are at hand and libraries can readily be generated. The strength of the approach lies in its simplicity, sensitivity to binding events, the tolerance to additives and the possibility of having several ligands in the assay. This study extends the increasing potential of selenium in structure biology and medicinal chemistry. We anticipate that SEAL by NMR will be a beneficial tool for the development of selenium‐based bioactive compounds, such as glycomimetic drug candidates.     

Thermal Stability of Biodegradable Films Based on Soy Protein and Corn Starch

Summary: In this paper, films were prepared from soy protein and corn starch in different proportions and thermal stability and kinetic parameters were determined through degradation reactions in an inert atmosphere. Solid residues and decomposition products were identified by infrared spectroscopy. Films from corn starch were less thermally stable than soy protein films. The films containing both components had lower thermal stabilities when compared to those of the pure biopolymers. The mechanism of starch thermal degradation seems to occur in a single step, which can be confirmed by the constant E-values during the thermal degradation reaction. For the pure protein and its mixtures an increase in the activation energy was observed during the reaction. Solid residues for protein at different temperatures showed mainly bands related to CO stretching, angular deformation of N H and C H groups. For starch, absorptions related to free and bound O H, CO stretching of CO₂, CO and carbonyl compounds were observed. For the 50/50 mixture bands related to soy protein and corn starch were observed. The gaseous products for soy protein showed absorptions related to CO₂, CO, CO, NH₃ and C H stretching. For pure starch absorptions related to O H stretching from alcohol, CO from CO₂, CO and carbonyl compounds. The 50/50 mixture had the same characteristics as pure soy protein and corn starch.     

New approach to stereochemical structure determination of bis-selenium-subsituted alkenes

A new approach to determination of the stereochemical structure of bis-selenium-substituted alkenes using experimental ⁷⁷Se NMR studies and B3LYP/6-311G(d) quantum-chemical calculations is developed. Joint analysis of experimental and calculated data allows assignment of signals in the ⁷⁷Se NMR spectrum. The method was evaluated taking the model compounds (PhSe)HC=C(SePh)R (R = COOMe, CH₂NMe₂, CH₂OH, Ph) as examples.     

Aminolysis of P-trichloro-N-dichlorophosphorylmonophosphazene and the crystal structure of 1-(dichlorophosphinyl)-2-chloro-2,2-bis(diisopropylamino)phosphazene

The reactions of Cl₃PN P(O)Cl₂ ( 1 ) with primary and secondary amines have been studied. The following monophosphazenes, (RRN)₃PN P(O)(NRR)₂, and bis(phosphinoyl)amines, [(RRN)₂P(O)]₂NH were isolated: NRR = NHCH₂Ph, Net₂, NH(CH₂)₂CH₃ groups for monophosphazenes, and Net₂, NH(CH₂)₂CH₃ for phosphinoyl amines. The unexpected geminal phosphazene, Cl(RRN)₂PN P(O)Cl₂, {RRN = N[CH(CH₃)₂]₂}, was also obtained in moderate yield. The spectral data (IR, ¹H, ¹³C, and ³¹P NMR, and MS) are presented. The structure of 1-(dichlorophosphinyl)-2-chloro-2,2-bis(diisopropylamino)phosphazene ( 5 ) was determined by X-ray crystallography. The basicities of these and related compounds in nonaqueous nitrobenzene solution were obtained by potentiometric titration.     

Formation,Structural Characterization,and Calculated NMR Chemical Shifts of Selenium‐Nitrogen Compounds from SeCl4 and ArNHLi (Ar = supermesityl,mesityl)

Supermesityl selenium diimide [Se{N(C₆H₂^tBu₃‐2, 4, 6)}₂; Se{N(mes*)}₂] can be prepared in a good yield from the reaction of SeCl₄ and (mes*)NHLi. The molecule adopts an unprecedented anti, anti‐conformation, as deduced by DFT calculations at PBE0/TZVP level of theory and supported by ⁷⁷Se NMR spectroscopy and a crystal structure determination. An analogous reaction involving (C₆H₂Me₃‐2, 4, 6)NHLi [(mes)NHLi] unexpectedly lead to the reduction of selenium and afforded the selenium diamide Se{NH(mes)}₂ that was characterized by X‐ray crystallography and ⁷⁷Se NMR spectroscopy. The Se‐N bonds of 1.847(3) and 1.852(3) Å show normal single bond lengths. The <NSeN bond angle of 109.9(1)° also indicates a tetrahedral AX₂E₂ bonding arrangement around selenium. Two N‐H···N hydrogen bonds link the Se{NH(mes)}₂ molecule with two discrete (mes)NH₂ molecules. In the solid state selenium diamide adopts the anti‐conformation, whereas in solution the presence of both syn‐ and anti‐isomers could be observed. PBE0/TZVP calculations of the shielding tensors of 28 different types of selenium‐containing molecules, for which the ⁷⁷Se chemical shifts are unambiguously known, were carried out to assist the spectral assignment of Se{N(mes*)}₂ and Se{NH(mes)}₂.     

Organoselenium compounds containing pyrazole or phenylthiazole groups: Synthesis,structure, tin(IV) complexes and antiproliferative activity

The diorganodiselenides (pzCH₂CH₂)₂Se₂ ( 1 ) and (PhtzCH₂)₂Se₂ ( 2 ) were prepared by reacting Na₂Se₂ with 1‐(2‐bromoethyl)‐1H‐pyrazole and 4‐(chloromethyl)‐2‐phenylthiazole, respectively, while the reactions between 1‐(2‐bromoethyl)‐1H‐pyrazole or 4‐(chloromethyl)‐2‐phenylthiazole and the lithium organoselenolates [2‐(Et₂NCH₂)C₆H₄]SeLi and [2‐{O(CH₂CH₂)₂NCH₂}C₆H₄]SeLi in a 1:1 molar ratio resulted in the heteroleptic diorganoselenium(II) compounds [2‐(Et₂NCH₂)C₆H₄](R)Se (R = pzCH₂CH₂ ( 3 ) or PhtzCH₂ ( 5 )) and [2‐{O(CH₂CH₂)₂NCH₂}C₆H₄](R)Se (R = pzCH₂CH₂ ( 4 ) or PhtzCH₂ ( 6 )). The diorganotin(IV) bis(organoselenolato) derivatives of type R₂Sn(SeCH₂CH₂pz)₂ (R = 2‐(Me₂NCH₂)C₆H₄ ( 7 ) or Me ( 8 )) were obtained by reacting (pzCH₂CH₂)SeNa with the appropriate diorganotin(IV)dichloride in a 2:1 molar ratio. All compounds were investigated using NMR spectroscopy (¹H, ¹³C, ⁷⁷Se, ¹¹⁹Sn as appropriate) and ESI+ mass spectrometry. The molecular structures of 2 and 6 were determined using single‐crystal X‐ray diffraction. The formation of a 10–Se–3 hypercoordinated species was evidenced for 6 in the solid state, as a consequence of the C,N coordination behaviour of the 2‐{O(CH₂CH₂)₂NCH₂}C₆H₄ group. Compounds 1 , 7 and 8 were investigated for their antiproliferative activity towards the mouse colon carcinoma C26 cell line with the preliminary results showing a better activity than 5‐fluorouracil.