Organodithiols including para-aryl dithiols (PADTs, HS-(C6H4)n-SH, n = 1, 2 and 3) and alpha, omega-alkanedithiols (ADTs, HS-(CH2)n-SH, n = 2, 4, …) with two distal thiols have been used extensively in molecular electronics, surface-enhanced Raman spectroscopy (SERS), and quantum electron tunneling between two gold or silver nanoparticles (AuNPs and AgNPs). The popular belief is that these dithiols cross-link noble metal nanoparticles (NPs) as monolayer dithiolate spacers. Reported is the finding that PADTs predominantly exist as monothiolate forms on AuNPs or AgNPs. No PADT-induced NP cross-linking was observed regardless of NP/PADT concentration ratios. 1,4-benzenedimethanethiol (HS-CH2-(C6H4)-CH2-SH) and ADT can be completely deprotonated, forming dithiolates on AuNPs and AgNPs, while only one PADT thiol can be deprotonated even when PADTs are treated with concentrated NaOH or AgNO3. AuNP localized surface plasmon resonance (LSPR) measurement provides conclusive evidence that ADT in AuNP junctions primarily consisted of dithiolate monomers in which the two sulfides are either attached to the same AuNP, or cross-link two adjacent AuNPs as single-molecular spacers. However, ADT molecules most likely in the area surrounding the AuNP junction are monothiolate with their distal thiols either remaining intact or forming disulfide cross-links with neighboring adsorbed ADTs. The possibility for ADT to cross-link two AgNPs as single molecular linker is excluded on the basis of TEM measurements that showed ADT-induced AgNP disintegration. This work highlights the difference between organothiol interactions with AgNPs and AuNPs and should be of broad importance for plasmonic NP research given the popularity of PADTs in molecular electronics and SERS applications.

Most pharmaceutically relevant proteins and many extracellular proteins contain disulfide bonds. Formation of the correct disulfide bonds is essential for stability in almost all cases. Disulfide containing proteins can be rapidly and inexpensively overexpressed in bacteria. However, the overexpressed proteins usually form aggregates inside the bacteria, called inclusion bodies, which contains inactive and non-native protein. To obtain native protein, inclusion bodies need to be isolated and resolubilized, and then the resulting protein refolded in vitro. In vitro protein folding is aided by the addition of a redox buffer, which is composed of a small molecule disulfide and/or a small molecule thiol. The most commonly used redox buffer contains reduced and oxidized glutathione. Recently, aliphatic dithiols and aromatic monothiols have been employed as redox buffers. Aliphatic dithiols improved the yield of native protein as compared to the aliphatic thiol, glutathione. Dithiols mimic the in vivo protein folding catalyst, protein disulfide isomerase, which has two thiols per active site. Furthermore, aromatic monothiols increased the folding rate and yield of lysozyme and RNase A relative to glutathione. By combining the beneficial properties of aliphatic dithiols and aromatic monothiols, aromatic dithiols were designed and were expected to increase in vitro protein folding rates and yields. Aromatic monothiols (1-4) and their corresponding disulfides (5-8), two series of ortho- and para-substituted ethylene glycol dithiols (9-15), and a series of aromatic quaternary ammonium salt dithiols (16-17) were synthesized on a multigram scale. Monothiols and disulfides (1-8) were utilized to fold lysozyme and bovine pancreatic trypsin inhibitor. Dithiols (11-17) were tested for their ability to fold lysozyme. At pH 7.0 and pH 8.0, and high protein concentration (1 mg/mL), aromatic dithiols (16, 17) and a monothiol (3) significantly enhanced the in vitro folding rate and yield of lysozyme relative to the aliphatic thiol, glutathione. Additionally, aromatic dithiols (16, 17) significantly enhance the folding yield as compared to the corresponding aromatic monothiol (3). Thus, the folding rate and yield enhancements achieved in in vitro protein folding at high protein concentration will decrease the volume of renaturation solution required for large scale processes and consequently reduce processing time and cost.

Neutral diorganotin compounds of the 1,3-dithiole-2-thione-4,5-dithiolate ligand have been prepared. The syntheses of Me₂Sndmit, Et₂Sndmit, Bu₂Sndmit, (C₈H₁₇)₂Sndmit, (C₁₀H₂₁)₂Sndmit and (C₁₄H₂₉)₂Sndmit are described. For the purposes of indicating the formation of different structural phases, D.S.C. powder patterns are reported for initial and recrystallised samples of Me₂Sndmit, Et₂Sndmit and Bu₂Sndmit. Since Et₂Sndmitshowed different tin environments by solid phase state N.M.R. and clearly different powder patterns after recrystallisation, the compound was recrystallised from various solvents in an attempt to determine how many crystalline forms exist. To date, two forms have been identified: orthorhombic and monoclinic. The single crystal X-ray structure analyses of these are described. It has also been shown that upon heating a transition from the orthorhombic to the monoclinic form occurs at 140°C. The crystal strict of Me₂Sndmit has also been determined and is reported, along with Mossbauer parameters for Me₂Sndmit and Me₂Sndmio (dmio = 1,3-dithiole-2-one-4,5-dithiolate). Anionic organotin bis-dmit complexes of the form [RSn(dmit)₂][Q]⁺ have also been prepared, with a view to investigating their electrochemical properties. The syntheses of complexes with R chain length ranging from 4 to 18 carbons are described. The problem of formation of [Sn(dmit)₃][Q]₂ is also discussed. D.S.C. curves and cyclic voltammograms for [C₁₄H₂₉Sn(dmit)₂][C₁₄H₂₉NMe₃] and [NEt₄][(dmit)₂SnC₁₀H₂₀Sn(dmit)₂][NEt₄] are also described. Chiral macrocycles have potential uses as catalysts for asymmetric bond-forming reactions and as selective to metal ions. A chiral macrocyclic derivative of dmit was synthesised from methyl-4,6-<I>O</I>-benzylidene-2,3-bis-<I>O</I>-[(2-iodoethoxyethyl)-ethyl]-α-D-glucopyranoside. Since reaction of this with dmit proved to be unexpectedly problematic, attempted reactions of the sugar derivative with Na₂dmit<I> in situ</I>, isolated Na₂dmit, [Zn(dmit)₂][NEt₄]₂, [Ph₂Sn(dmit)I][NEt₄] and Cs₂dmit are described.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The organotellurium compounds have been the subject of research due to their pharmacological and toxicological properties. It is believed that the main mechanism involved in the toxicity of these compounds is the ability to interact with sulfhydryl groups from molecules biologically active. Beyond the toxicological effects, some pharmacological properties have been attributed to organotellurium compounds. This study aimed to investigate the potential toxicological and pharmacologic of 2-phenylethynyl-butyltellurium (PEBT) through experiments in vitro and in vivo in rodents. To evaluate the toxicological effect the PEBT was used at different concentrations in the oxidation of mono and dithiols and analysis of enzyme Na+K+ -ATPase and lactate dehydrogenase in vitro. Furthermore, lethality studies were performed to calculate the LC50 LD50 of this compound and for better understanding their toxicity. To evaluate the pharmacological effect the PEBT was used at a dose of 1mg/kg 30 minutes before the behavioral experiments, evaluation of locomotor activity, forced swim test (FST) and the tail suspension test (TST), immediately after testing the cerebral cortex was removed for analysis of monoamine oxidase (MAO) enzyme. The results showed that the PEBT oxidized thiols of low molecular weight and inhibits the activity of the enzyme Na+K+ - ATPase by oxidation of sulfhydryl groups, and such oxidation is dependent on the tellurium atom in the structure of this compound. Moreover, the acute administration of PEBT showed an antidepressant-like effect on TNF in mice, as well inhibits the activity of MAO-A enzyme in the cerebral cortex, demonstrating the involvement of this enzyme in its antidepressant-like effect. / Os compostos orgânicos de telúrio têm despertado o interesse dos pesquisadores, devido as suas propriedades farmacológicas e toxicológicas. Acredita-se que o principal mecanismo envolvido na toxicidade desses compostos, seja a capacidade de interagir com os grupamentos sulfidrílicos de moléculas biologicamente ativas. Além dos efeitos toxicológicos, propriedades farmacológicas vêm sendo atribuídas aos compostos orgânicos de telúrio. Esse estudo teve como objetivo investigar o potencial toxicológico e farmacológico do 2- feniletinilbutil-telúrio (PEBT), através de experimentos in vitro e in vivo em roedores. Para a avaliação toxicológica, o PEBT foi utilizado em diferentes concentrações na oxidação de mono e ditiois e na determinação da atividade das enzimas Na+K+ -ATPase e lactato desidrogenase, in vitro. Ainda nesse sentido estudos de letalidade foram realizados para calcular a CL50 e DL50 desse composto para melhor compreender a sua toxicidade. Para a avaliação farmacológica, o PEBT foi administrado em camundongos, na dose de 1 mg/kg 30 minutos antes dos experimentos comportamentais, avaliação da atividade locomotora, teste do nado forçado (TNF) e teste de suspensão da cauda (TSC). Após os testes comportamentais, os animais foram mortos e o córtex cerebral foi retirado para determinação da atividade da enzima monoamina oxidase (MAO). Os resultados mostraram que o PEBT oxida tióis de baixo peso molecular e inibe a atividade da enzima Na+K+ -ATPase, pela oxidação de seus grupamentos sulfidrilicos, sendo essa oxidação depende da presença do átomo de telúrio na estrutura do composto. Além disso, a administração aguda do PEBT produz um efeito do tipo antidepressivo no TNF em camundongos, bem como inibe a atividade da enzima MAO-A em córtex cerebral, demonstrando o envolvimento dessa enzima no seu efeito do tipo antidepressivo.