Electrospray ionization and triple quadrupole tandem mass spectrometry study of some biologically relevant homo- and heterodimeric cadmium thiolate conjugates

A series of 19 compounds of general formula R₁S-Cd-SR₂, R₁, and R₂, being some biologically relevant thiol amino acids and peptides, were prepared by direct reaction of cadmium(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of stoichiometric 1:2 Cd-thiol systems containing either an individual thiol or equimolar mixtures of two different thiols featured several Cd-containing signals, although at much lesser intensity than in the previously reported experiments with mercury(II) (J. Am. Soc. Mass Spectrom. 2004, 15, 288–300). Also, the relative intensity of the homo- and heterodimeric thiolates were significantly different from the theoretically expected 1:2:1 ratio, thus pointing at some degree of discrimination between the different thiols. In particular, homo-cysteine showed much less reactivity than cysteine, and penicillamine and cysteine methyl ester much less than the free amino acid. The fragment spectra show structure-specific ions for the different ligands bound to the metal ion and allow a stand-alone determination of the connectivity also of isomeric pairs. The fragmentation pathways are similar to those observed for the corresponding mercury(II) analogues, with the addition of further intense and specific fragments, one formally carrying a Cd-bound OH ligand and one connected as a five-membered oxazolone carrying a cadmium-bis-thiolate side chain, both formed with a high intensity. Energy-resolved fragmentation data show that metal-free ions can be generated from cysteine but not from glutathione conjugates and point to the possibility of unveiling differences in the biochemical behavior of the conjugates of different heavy metals through the detailed study of their mass spectrometric fragmentation.     

Synthesis of Novel Thioethers and Sulfoxide Compounds

Abstract

Thiosubstituted butadiene and butenyne compounds were synthesized from the reactions of 1,1,3,3,4,4-hexachloro-1-butene or 1,1,2,4,4-pentachlorobuta-1,3-diene with different thiols in EtOH/H₂O solution of NaOH. Tris(thio)substituted butadiene compound was treated with potassium tert-butoxide to obtain tris(thio)substituted butatrienyl halide compound. The novel sulfoxide compounds were synthesized from the reactions of polyhalobutadiene compounds with aliphatic thiols in CHCl₃ with m-CPBA at 0°C. The structures of the novel compounds were characterized by micro analysis, FT-IR, ¹H-NMR, ¹³C-NMR, and MS.     

Highly Regioselective Ring Opening of Epoxides with Thiols Catalyzed by SbCl3 Under Solvent-Free Conditions

The ring-opening reaction of epoxides with thiols by SbCl ₃ supported on Kieselguhr under solvent-free conditions, afforded high yields of β-hydroxy sulfides. Nucleophilic attack of the thiols occurs regioselectively at the less hindered side of the epoxides.     

Multifunctional iron thiocarboxylate complexes: synthesis,reactivity and structure of CpFe(CO)<Subscript>2</Subscript>SCO-3,5-C<Subscript>6</Subscript>H<Subscript>4</Subscript>(COCl)<Subscript>2</Subscript>

A controlled substitution reaction of the chlorine atoms of 1,3,5-benzenetricarbonyl trichloride by the organoiron fragment (CpFe(CO)₂S) has been achieved. The complexes CpFe(CO)₂SCO-3,5-C₆H₃(COCl)₂ (1), 1,3-[CpFe(CO)₂SCO]₂-5-C₆H₃COCl (2) and 1,3,5-[CpFe(CO)₂SCO]₃C₆H₃ (3) were prepared from the reaction of (μ-S _x )[CpFe(CO)₂]₂ (x = 3, 4) with 1,3,5-C₆H₃(COCl)₃ in a 1:1, 2:1, or 3:1 metal to ligand molar ratio. The reactions of (1) with amines, thiols, and carboxylic acids produce the trifunctional mono-iron complexes CpFe(CO)₂SCO-3,5-C₆H₃(COY)₂ [Y = NR₂ (4), SR (5), OCOR (4)]. The X-ray structure determination of (1) is reported.     

η6-Arenetricarbonylchromium(0) Complexes in the Synthesis of 1,4-Benzodiazepines and Its Nucleophilic Substituted Products

Abstract

7-Chloro-5-carbomethoxy-1,3-dihydro-2H-1,4-benzodiazepines and its nucleophilic substituted products were synthesized via η⁶-arenetricarbonylchromium(0) intermediates. Ring enlargement of 5-chloro-N-chloroacetylisatin with hexamine in presence of Cr(CO)₆ led to the formation of 7-chloro-5-carbomethoxy-1,3-dihydro-2H-1,4-benzodiazepine in good yield with reduced reaction time. Nucleophilic substitutions on arene ring of η⁶-arenetricarbonylchromium(0) complexes with thiols, phenol, and primary amines were successfully carried out in decalin medium.     

One‐Pot Synthesis of Sulfonamides and Sulfonyl Azides from Thiols using Chloramine‐T

A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols was accomplished by oxidation with chloramine‐T (=N‐chlorotosylamide=N‐chloro‐4‐methylbenzenesulfonamide), tetrabutylammonium chloride (Bu₄NCl), and H₂O. The sulfonyl chlorides were then further allowed to react with excess amine or NaN₃ in the same pot.     

(NH4)6Mo7O24·4H2O as an Efficient,Selective, and Reusable Catalyst for the Oxidation of Thiols to Disulfides Using Potassium Bromate

Abstract

Ammonium molybdate, (NH₄)₆Mo₇O₂₄·4H₂O, is found to be an efficient and selective catalyst for the oxidation of thiols to corresponding disulfides using potassium bromate in aqueous acetonitrile as the solvent. Among various solvents tested, CH₃CN/H₂O showed better results in terms of the reaction yield and rate. In the absence of (NH₄)₆Mo₇O₂₄·4H₂O, the oxidation reaction is not selective for the formation of disulfides. The catalyst can be easily recovered after completion of the reaction and reused without any significant loss of its activity.

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

THE SULFUR (11)-NITROGEN BOND. PART IV1. AMINOSULFENATES

Abstract

Aminosulfenates R₂NSOR' have been prepared from aminosulfenyl chlorides and tin alkoxides. They form sulfenyl chlorides with chlorosilanes, bisaminosulfides with secondary amines and polysulfides with thiols.     

Study of the reactions of 3-chloro-4-cyanobenzo[b][1,6]naphthyridine with nucleophilic reagents

The reactions of 3-chloro-4-cyanobenzo[b][1,6]naphthyridine (4) with S-, C-, and N-nucleophiles afford stable s-adducts at position 10. In the base-catalyzed reactions of compound 4 with thiols, the resulting -complexes are rearranged into sulfides 14a—c. Sulfides 14b,c undergo the Thorpe—Ziegler cyclization to give 1-aminobenzo[b]thieno[2,3-h][1,6]naphthyridine derivatives 15a,b. The reaction of naphthyridine 4 with aniline affords a mixture of -adducts of the C—N and C—C types, while those with aliphatic amines yield 3-amino derivatives 17a—c. In the presence of H₂O₂, benzonaphthyridine 4 adds peroxycarboxylic acids to give compounds 8a,b. In alkaline medium, adduct 8a is rearranged into 4-aminopyridine-3-carbaldehyde derivative 10.     

Convenient Synthesis of 2,4-Disubstituted Tetrahydrothiophenes from Mannich's Adducts

Ammonium salts of β-functionalized allylic amines 1 were successfully employed as electrophilic agents with functional thiols. The obtained intermediate 2 underwent intramolecular cyclization in the presence of potassium tert-butoxide to afford 2,4-disubstituted tetrahydrothiophenes 3.     

Perfluoroalkylation of 2-Thiopyrimidine Derivatives

The method of perfluoroalkylation of heterocyclic thiols and disulfides by thermolytic reaction with xenon(II) bisperfluoroalkylcarboxylates has been extended to sulfur-containing pyrimidines, including 2-mercaptopyrimidines, symmetrical disulfides, and S-trifluoroacetyl derivatives obtained from the corresponding thiols. The main reaction products are 2-SC_nF_2n+1 (n = 1, 2)-substituted pyrimidines. Their formation proceeds only via disulfides into which the initial thiols and S-trifluoroacetyl derivatives are converted in the reaction medium. Side reactions occurred in the case of trifluoromethylation linked with the perfluoroalkylation of the pyrimidine nucleus at the free 5 position (in the case of the 4,6-dimethyl derivative), or at position 4 or 4 and 5 (for unsubstituted pyrimidine). In addition, the introduction of the CF₃ group at one of the methyl substituents was confirmed by the formation of CH₂CF₃ fragment.     

Vanadium Catalyst for C- and S-Alkylation of Benzhydrols in Water: An Experimental Study and Green Metrics Evaluation

A strategy for the vanadium-catalyzed dehydrative C- and S-alkylation by nucleophilic substitution of benzhydrols with arenes and thiols is reported. The alkylation was achieved with the divanadium oxoperoxo complex [K₃(V⁺⁵)₂(O₂²⁻⁾₄(O²⁻)₂(μ-OH)] in water under air. The newly developed transformation could accommodate a broad substrate scope, including (hetero)arenes and thiols (34 examples). Both the symmetrical and unsymmetrical benzhydrols furnished excellent yields of the alkylated product under mild reaction conditions. The scope of this strategy was further extended to synthesize bis-benzylated arenes (poly-arylated products) in high yields and regioselectivities. The green metrics determination of all the alkylated products suggests the technical and environmental benefits of the present protocol. The longevity experiment reveals the catalytic activity was maintained over seven cycles. To understand the mechanism of the present reaction, spectroscopic and kinetic studies were undertaken. This simple protocol, which affords the desired products with water as the by-product, can be achieved under mild conditions without needing a base or other additives.     

Synthesis and Cytotoxicity of 3-(Hetarylthio)-1-propynyl(trimethyl)silanes

We have developed a two-step method for synthesis of 3-(hetarylthio)-1-propynyl(trimethyl)silanes from thiols in a phase-transfer catalysis system HCCCH₂Br-solid K₂CO₃-18-crown-6-toluene followed by reaction with n-BuLi-Me₃SiCl in ether or THF. We have observed that 3-[1,3-bis(trimethylsilyl)-2-propynyl]thioindole displays high cytotoxicity in HT-1080 and MG-22A tumor cell lines.     

Acyl iodides in organic synthesis. Reaction of acetyl iodide with thiols

The direction of reactions of acetyl iodide with aliphatic, aromatic, and heterocyclic thiols is determined by the thiol acidity and steric factors. Acetyl iodide reacted with aliphatic thiols, including trialkylsilylsubstituted derivatives R(CH₂) _n SH (R = Me, n = 3; R = Me₃Si, n = 3; R = Et₃Si, n = 2), to give the corresponding ethanethioates R(CH₂) _n SCOMe. Benzenethiol was oxidized with acetyl iodide to diphenyl disulfide. The reaction of acetyl iodide with 2-sulfanylethanol afforded 2-(2-iodoethyldisulfanyl)ethyl acetate as a result of three consecutive-parallel processes: acylation, iodination, and oxidation of the initial compound. 1,3-Benzothiazole-2-thiol reacted with acetyl iodide only at the nitrogen atom to give quaternary salt, whereas the SH group remained intact.     

KINETICS AND MECHANISM OF COMPLEX FORMATION BETWEEN [PtCl(DIEN)]+ AND THIOLS AND THIOETHERS

Abstract

Reactions of the monofunctional platinum(II) complex, [PtCl(dien)]⁺, with different thiols and thioethers, including biologically important molecules, have been studied as a function of temperature (288.2–308.2K) using conventional electronic spectrophotometry in 0.10 M aqueous hydrochloric acid and by ¹H NMR spectroscopy. The second-order rate constants, k₂, are similar, varying between 1.43 × 10^?3 and 46.1 × 10^?3 M^?1s^?1 at 25°C. The reactivity follows the sequences: D-penicillamine ≤ L-cysteine ≤ glutathione ≤ thiodiglycolic acid ≤ thioglycolic acid ≤ L-methionine ≤ S-methylthioglycolic acid ≤ glycyl-D,L-methionine. However, variation in size, bulkiness and solvation of the entering ligands reflect in their properties as nucleophiles. Large negative values of the entropy of activation (ΔS≠), between ?140 and ?190 J K^?1 mol^?1, indicate that all thiols and thioethers react via the same associative mechanism. Results have been analyzed in relation to the antitumor activity and toxicity of platinum(II) complexes.     

Facile Stereoselective Synthesis of (E)-1-Arylseleno-Substituted 1,3-Enynes and Their Applications in Synthesis of (E)-Enediynes

(E)-1-Iodo-2-arylselenoethylenes 1 underwent the Sonogashira coupling reactions with terminal alkynes 2 to afford (E)-1-arylseleno-substituted 1,3-enynes 3 in high yields. (E)-1-Arylseleno-substituted 1,3-enynes 3 were coupled with alkynylmagnesium bromides 4 in the presence of a catalytic amount of NiCl₂(PPh₃)₂ to give stereoselectively (E)-enediynes 5 in good yields.     

BIOLOGICAL DEACTIVATION AND SINGLE-STRAND BREAKAGE OF PLASMID DNA BY PHOTOSENSITIZATION USING TRIS(2,2''- BIPYRIDYL)RUTHENIUM(II) AND PEROXYDISULFATE

Abstract— Single-strand break formation and biological deactivation of plasmid pBR322 DNA in the presence of tris(2,2′-bipyridyl)-ruthenium(II), Ru(bpy)2/3;⁺, and K₂S₂O₈, upon irradiation with visible light(400–500 nm), were studied in aqueous solution at room temperature. Conditions of complete binding of Ru(bpy)2/3;⁺ to the strand were employed. The damage is initiated mainly by the SO^2/3;; radical anion. Under anoxic conditions at a ratio of nucleotide to sensitizer concentrations (N/S) of 18 and S₂O2/8^- concentrations of 0.5 mM the quantum yield of single-strand break (ssb) formation is φ_ssb= 8.4 times 10^-3 while that of biological deactivation (bd) is Ø_bd= 7.6 times 10^-3 (φ_ssb= 5.2 times 10^-36.4 times 10^-3, 6.0 times 10^-3 and φ_bd= 4.2 times 10^-3, 5.2 times 10^-3, 4.8 times 10^-3 at N/S=3, 6, and 9, respectively). The quantum yields are approximately 2.5 times smaller in air-saturated solutions. At N/S = 18 about 33 SO₄^-radical anions are required per one lethal event. φ_bd increases linearly with the S₂Oφ^- concentration (up to 0.5 mM). The damage to DNA is drastically reduced on addition of mono- or divalent salts (e.g. NaC10₄, MgCl₂). These additives cause the release of Ru(bpy)2⁺ from the strand. The observed damage to DNA is thus the result of a site specific reaction. When the phenanthroline analogue, Ru(phen)φ⁺, is used as sensitizer, φ_ssb and φ_bd are three times smaller.     

Rapid and Convenient Method for the Synthesis of Symmetrical Disulfides

Abstract

We present here the results on the use of 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-hexachloride as an efficient promoter in the conversion of thiols to the corresponding symmetrical disulfides under solvent-free conditions. Aromatic thiols bearing electron donating and electron withdrawing groups, heteroaromatic, and alkyl thiols reacted efficiently to afford excellent yields of disulfides in short reaction times after easy work-up. Different functional groups including carboxyl, methoxy, methylthio, and halogen are tolerated.

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

基于[LnMo12]二十面体的三维稀土钼酸盐骨架的合成、结构及荧光性能

通过缓慢蒸发溶剂法合成了2例新的三维稀土钼酸盐：[Ln (H₂O)₃]₃[LnMo₁₂O₄₂]·xH₂O,其中Ln=Eu (1)、Tb (2),x=7(1),10.17(2)。这2种稀土钼酸盐中都含有新颖的二十面体[LnMo₁₂O₄₂]构建单元,该单元通过与{LnO₉}多面体进一步连接形成三维网络。光致发光测试表明,化合物1和2显示出明显不同的发射特征,这与Eu³⁺和Tb³⁺离子的不同能级跃迁密切相关。化合物1表现出较强的红色发射(CIE色度坐标为(0.66,0.33))、高发光强度、较大的荧光量子产率(约60%),对应于从⁵D0到⁷F_J (J=4、3、2、1、0)的跃迁;化合物2表现出浅绿色发射(CIE色度坐标为(0.34,0.60)),对应从⁵D₄到⁷F_J (J=6、5、4、3)的能级跃迁,其发光强度较弱和荧光量子产率较低(约20%)。有趣的是,一定量的Tb³⁺引入和大量溶剂分子的存在导致化合物2发生部分荧光猝灭,但对化合物1的荧光几乎没有影响。     

内嵌镧金属富勒烯的高产率合成及异构体比例调控

采用电弧放电法制备内嵌镧金属富勒烯的原灰,通过改变氦气压力及电流强度来提高内嵌镧金属富勒烯产率。原灰由1,2,4-三氯苯提取并回溶入甲苯后,利用分析型高相液相色谱（HPLC）对提取液中各富勒烯组分进行分析。通过分别衡量3种常见含镧金属富勒烯La@C_2v-C₈₂、La@C_s-C₈₂和La₂@C₈₀与C₈₄的相对峰面积比,探讨了氦气压力和电流强度等对3种金属富勒烯产率的影响。实验结果表明,氦气压力与电流强度共同决定了金属富勒烯的产率,在（1）低电流高氦气压、（2）中等电流中等氦气压、（3）高电流低氦气压的条件下都可以高产率地获得含镧金属富勒烯。此外,调整电流强度和氦气压力可以改变La@C_2v-C₈₂和La@C_s-C₈₂的相对比例。例如,在电流为100、120 A或氦气压为20、35 kPa时,此前认为的"minor"异构体La@C_s-C₈₂的含量甚至高于"major"异构体La@C_2v-C₈₂。我们还发现,降低电流强度或减小氦气压力可促进La₂@C₈₀的生成,这表明La₂@C₈₀与La@C₈₂的形成过程可能是不同的。