Peptide Hydrolysis by Metal-Cyclen Complexes and Their Analogues: Insights from Theoretical Studies
详细信息 查看全文
- 作者：Tingting Zhang ; Xiaoxia Zhu ; Rajeev Prabhakar
- 刊名：Organometallics
- 出版年：2014
- 出版时间：April 28, 2014
- 年：2014
- 卷：33
- 期：8
- 页码：1925-1935
- 全文大小：768K
- 年卷期：v.33,no.8(April 28, 2014)
- ISSN：1520-6041
文摘
In the present DFT study, mechanisms of peptide hydrolysis by Co(III)- and Cu(II)-containing complexes of 1,4,7,10-tetraazacyclododecane (cyclen), 1-Co and 1-Cu, respectively, and 1-oxa-4,7,10-triazacyclododecane (oxacyclen), 2-Co and 2-Cu, respectively, and their analogues have been investigated. In addition, the effects of the ligand environment, pendant (an organic group containing a recognition site) and metal ion (Co(III), Cu(II), Ni(II), Zn(II), Cd(II), and Pd(II)), on the energetics of this reaction have been elucidated. The reactant of the 1-Co complex exists in the syn鈥揳nti conformation, while that of 1-Cu in the syn鈥搒yn form. For both these complexes, stepwise and concerted mechanisms were found to occur with similar barriers. The substitution of one of the nitrogen atoms in the cyclen macrocycle to create oxacyclen should occur at position 10 in the Co(III) case and at position 4 in the Cu(II) case. A comparison between the barriers using the common conformation (syn鈥揳nti) of 1-Co and 2-Co showed that both complexes hydrolyze the peptide bond with similar barriers, i.e., 39.8 kcal/mol for the former and 40.1 kcal/mol for the latter. This result is in line with the measured data that suggest that the oxacyclen complex exhibits just four times greater activity than the cyclen complex. The removal of the pendant (鈭扖2H5) group in the Co(III)- and Cu(II)-cyclen complexes (1鈥?b>-Co and 1鈥?b>-Cu, respectively) reduced the barriers by 9.3 and 3.0 kcal/mol, respectively. For 1鈥?b>-Co, the barrier of 30.5 kcal/mol is in agreement with the experimental value of 25.9 kcal/mol for the cleavage of myoglobin at pH 9.0 and 50 掳C. The reactants of 1鈥?b>-Cu, 1鈥?b>-Zn, 1鈥?b>-Pd, and 1鈥?b>-Cd adopt the syn鈥搒yn conformation, whereas 1鈥?b>-Ni and 1鈥?b>-Co exist in the syn鈥揳nti geometry. The barriers for 1鈥?b>-Ni (triplet spin state), 1鈥?b>-Cu (doublet spin state), 1鈥?b>-Cd (singlet spin state), 1鈥?b>-Co (singlet spin state), and 1鈥?b>-Zn (singlet spin state) are similar, i.e., 27.2, 29.7, 30.5, 30.5, and 31.9 kcal/mol, respectively, and the highest barrier (41.5 kcal/mol) is computed for 1鈥?b>-Pd (singlet spin state).