Synthesis of Reusable Silica Nanosphere-Supported Pt(IV) Complex for Formation of Disulfide Bonds in Peptides

Molecules. 2017 Feb 22;22(2):338. doi: 10.3390/molecules22020338.


Some peptide-based drugs, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bond. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO₂@TPEA@Pt(IV)); TPEA: N-[3-(trimethoxysilyl)propyl]ethylenediamine) was synthesized via a four-step procedure and was used for the formation of intramolecular disulfide bonds in peptides. Transmission electron microscopy (TEM) and chemical mapping results for the Pt(II) intermediates and for SiO₂@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly-distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by X-ray photoelectron spectroscopy (XPS). The Pt(IV) loaded on SiO₂@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-VIS spectrometry. The formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by the use of SiO₂@TPEA@Pt(IV) was investigated, and the relative oxidation yields were determined by high-performance liquid chromatography (HPLC). In addition, peptide 1 (Ac-CPFC-NH₂) was utilized to study the reusability of SiO₂@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO₂@TPEA@Pt(IV) after being used for ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Keywords: intramolecular disulfide; monodisperse silica nanospheres; peptide; reusability; supported platinum(IV) complex.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Coordination Complexes / chemistry*
  • Disulfides / chemistry*
  • Nanospheres / chemistry*
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Peptides / chemistry*
  • Photoelectron Spectroscopy
  • Platinum / chemistry*
  • Silicon Dioxide / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Sulfhydryl Compounds / chemistry


  • Coordination Complexes
  • Disulfides
  • Oxidants
  • Peptides
  • Sulfhydryl Compounds
  • Platinum
  • Silicon Dioxide