Banca de DEFESA: SAMUEL SANTOS DE OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : SAMUEL SANTOS DE OLIVEIRA
DATE: 17/03/2023
TIME: 13:00
LOCAL: Exame remoto através da plataforma Google Meet em meet.google.com/tnr-gqcz-jeu
TITLE:

Modification and characterization of organochalcogenide-modified surfaces and evaluation of its properties.

PAGES: 226
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

The bioactivity of organic compounds of selenium and tellurium has increased in literature for the last two decades; the chalcogen oxidation state is modulating these properties. The divalent chalcogen derivatives are recognized as antioxidant agents. Still, the hypervalent compounds can also exhibit particular reactivities towards nucleophiles. As can be seen in the inhibition of thiol-dependent enzymes and cysteine proteases, those are recognized therapeutic targets for some diseases. The known biological targets for these compounds are restricted to available biological models studied so far using besides recombinant enzymes in buffered media and the monitoring of certain enzymatic activities in cellular systems. Besides that, it is necessary to capture and characterize biomolecules to expand the biological targets.

We proposed herein the use of organochalcogenides functionalized agarose for the isolation of biothiols, using papain as a model protein. The organochalcogen-functionalized agarose was able to retain papain after the oxidation of the chalcogenide to the corresponding oxide for H2O2, and the retained protein eluted using a dithiothreitol (DTT) solution as the mobile phase. The elution has different elution for ligand selenide or a telluride. The oxidation of selenides or tellurides to the respective oxides is a process widely reported in the literature; nevertheless, it is not known how this reaction occurs in heterogeneous phase and, therefore, it was necessary to study oxidation in more detail, as well as the reduction using thiols of low molecular weight.
To answer these questions the present work is divided into four fronts:, (i) the synthesis, (ii) the characterization of organochalcogenide immobilized at a solid surface in order to use it in bioconjugation with biothiols (papain, cathepsin), (iii) the characterization of oxidation and reduction kinetics, together with the characterization of enzyme inhibition and (iv) spectroscopic studies with UV-vis, FTIR and Raman techniques. The results obtained for the kinetic characterization of the reaction was important to recognize the reaction conditions necessary to promote the oxidation of chalcogenides and to measure the differences in reactivity between selenides and tellurides. Furthermore, it was observed that the oxidation time of the chalcogenide in aqueous solution with 20% methanol is shorter if compared to that solubilized in aqueous solution. The reduction of chalcogenoxides using low molecular weight thiols (N-acetylcysteine and captopril) was monitored by HPLC, and, in all cases, the complete reduction of oxides to the corresponding chalcogenides was observed in 30 minutes. The inhibition of papain by telluroxides has been shown to be irreversible with IC50 values in the order of nanomolar being the succinic derivative more effective inhibitor than the amino derivative, and this can be explained by the presence of amide groups that make the first derivative more similar to the natural substrates of protease. At the moment, the characterization of meta and ortho derivatives of the chalcogenides and the experimental vibrational characterization is underway, accompanied by ab initio simulations of the complete collection of compounds; this will allow a better characterization of the functionalized matrices.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1623562 - RODRIGO LUIZ OLIVEIRA RODRIGUES CUNHA
Membro Titular - Examinador(a) Externo ao Programa - 1802150 - MARCO ANTONIO BUENO FILHO
Membro Titular - Examinador(a) Externo à Instituição - CLEVERSON ROGÉRIO PRINCIVAL
Membro Titular - Examinador(a) Externo à Instituição - FÁBIO RODRIGUES
Membro Titular - Examinador(a) Externo à Instituição - KLEBER THIAGO DE OLIVEIRA - UFSCAR
Membro Suplente - Examinador(a) Interno ao Programa - 1762430 - DALMO MANDELLI
Membro Suplente - Examinador(a) Externo à Instituição - DOUGLAS GALANTE
Membro Suplente - Examinador(a) Externo à Instituição - JAMAL RAFIQUE