Efficient Oxidation of Thiols to Corresponding Disulfides Catalyzed by Hemin†

doi:10.7503/cjcu20160940

Abstract

Abstract:

Hemin was used as a catalyst for the oxidation of thiols to corresponding disulfides. The addition of N,N-diisopropylethylamine(DIEA) can enhance the hemin catalytic activity and decrease the hemin self-oxidative degradation during the catalytic process. The methyl thioglycolate was quickly oxidized to corresponding disulfide product(completed 90% in 20 min) in the presence of 1/4 hemin in aqueous solution(pH=8.0) and DIEA involved in the reaction as an axial ligand. The oxidation was carried out at room temperature(ca. 20 ℃) under atmosphere condition. And this catalytic system was also successfully applied in disulfide bond formation in peptide synthesis. Oxytocin and linaclotide were used as model peptide. Compared with conventional oxidation reagents, the notable feature of this catalytic system is green and efficient, which provides an alternative way to formating disulfide bond in peptide synthesis.

Key words: Hemin, Oxidation, Disulfide, Oxytocin, Linaclotide

CLC Number:

O629.72

TrendMD:

GE Weiwei, CHEN Jing, ZONG Liang, LI Jian, SUI Shaohui, WU Weihui, ZHANG Ming, DONG Junjun. Efficient Oxidation of Thiols to Corresponding Disulfides Catalyzed by Hemin^†[J]. Chem. J. Chinese Universities, 2017, 38(6): 1052.

Figures/Tables 8

Table 1 Parameters of methyl thioglycolate standard solution

Standard	V(Buffer)/mL	Amount of methyl thioglycolate	Final concentration /(mmol·L^-1)
A	100	13.6 μL	1.5
B	5	25 mL of Standard A	1.25
C	10	20 mL of Standard A	1.0
D	15	15 mL of Standard A	0.75
E	20	10 mL of Standard A	0.5
F	25	5 mL of Standard A	0.25
G	30	0	0(Blank)

Table 2 Parameters for hemin and thialglycolate system*

n(Hemin)∶n(Thiol)	V(Buffer)/mL	V(Hemin)/mL	V(Methyl thioglycolate)/μL
0	50	0	4.6
1∶20	50	0.25	4.6
1∶10	50	0.5	4.6
1∶4	50	1.25	4.6
1∶2.5	50	2.0	4.6
1∶2	50	2.5	4.6
1∶1000	50	0.25	227.5

Fig.1 Concentration of hemin vs. time required for thiol concentration consumed

Fig.2 Different axial ligands vs. time required for thiol concentration consumed

Fig.3 UV-Vis spectra of hemin in the presence of different axial ligands in oxidation reactiona. Blank; b. DIEA; c. trimethylamine; d. DMF.

Scheme 1 Possible catalytic reaction pathway for thiol oxidations catalyzed by hemin

Fig.4 HPLC chromatograms of linear oxytocin(A) and cyclic oxytocin(B)

Fig.5 HPLC chromatograms of linear linaclotide(A) and cyclic linaclotide(B)

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