The catalase family of enzymes,which include a variety with a binuclear manganese active site,mitigate the risk from reactive oxygen species by facilitating the disproportionation of hydrogen peroxide into molecular o...The catalase family of enzymes,which include a variety with a binuclear manganese active site,mitigate the risk from reactive oxygen species by facilitating the disproportionation of hydrogen peroxide into molecular oxygen and water.In this work,hydrogen peroxide disproportionation using complexes formed between manganese and cyclen or pyclen were investigated due to the spectroscopic similarities with the native MnCAT enzyme.Potentiometric titrations were used to construct speciation diagrams that identify the manganese complex compositions at different pH values.Each complex behaves as a functional mimic of catalase enzymes.UV-visible spectroscopic investigations of the H_(2)O_(2)decomposition reaction yielded information about the structure of the initial catalyst and intermediates that include monomeric and dimeric species.The results indicate that rigidity imparted by the pyridine ring of pyclen is a key factor in increased TON and TOF values measured compared to cyclen.展开更多
A new potential Zn^(Ⅱ)responsive Mn^(Ⅱ)-based MRI CA candidate derived from pyclen-3,9-diacetate(3,9-PC2A)has been synthesized and it possesses a di-(2-picolyl)amine(DPA)moiety as an active arm.The PC2A-DPA ligand w...A new potential Zn^(Ⅱ)responsive Mn^(Ⅱ)-based MRI CA candidate derived from pyclen-3,9-diacetate(3,9-PC2A)has been synthesized and it possesses a di-(2-picolyl)amine(DPA)moiety as an active arm.The PC2A-DPA ligand was found to form a thermodynamically stable complex with Mn^(Ⅱ)(log K_(MnL)=15.87(6)which translates into a pMn of 8.79)which also possesses outstanding inertness towards Zn^(Ⅱ)ion triggered transmetallation(t_(1/2)at pH=6.0 is 64.5 h).The[Mn(PC2A-DPA)]complex has a relatively high relaxation rate(3.11 s^(−1)at 1.41 T and 37℃for a 0.96 mM complex)which is not affected by the Zn^(Ⅱ)concentration directly,yet in the co-presence of 0.7 mM human serum albumin(HSA)the relaxation rate values(both R_(1)and R_(2))increased significantly(9.08 s^(−1)at 1.41 T and 37℃,for a 0.748 mM complex)owing to the efficient binding of the complex to the protein(log K_(aff)=3.5±0.1 M−1).The increase is large enough to visualize it by MR imaging using phantoms in vitro while preliminary in vivo MRI experiments confirmed that the glucose stimulated Zn^(Ⅱ)secretion(GSZS)can be visualized in the prostate of a healthy mouse.展开更多
基金financial support from the National Institute of Health(NIGMS,R15GM123463 to K.N.G.and GM117511-02 to B.S.P.)the National Science Foundation(CHE,1709369 to B.S.P.)+2 种基金financial support from TCU Andrews Institute of Mathematics&Science Education(to K.G.)Cambridge Isotope Laboratories,and TCU Research and Creativity Activity Grant(to K.G.)start-up funding from Texas Christian University for support of this work.
文摘The catalase family of enzymes,which include a variety with a binuclear manganese active site,mitigate the risk from reactive oxygen species by facilitating the disproportionation of hydrogen peroxide into molecular oxygen and water.In this work,hydrogen peroxide disproportionation using complexes formed between manganese and cyclen or pyclen were investigated due to the spectroscopic similarities with the native MnCAT enzyme.Potentiometric titrations were used to construct speciation diagrams that identify the manganese complex compositions at different pH values.Each complex behaves as a functional mimic of catalase enzymes.UV-visible spectroscopic investigations of the H_(2)O_(2)decomposition reaction yielded information about the structure of the initial catalyst and intermediates that include monomeric and dimeric species.The results indicate that rigidity imparted by the pyridine ring of pyclen is a key factor in increased TON and TOF values measured compared to cyclen.
基金the financial support from the Hungarian National Research,Development and Innovation Office(NKFIH K-120224,134694 and FK-134551 projects)the University of Debrecen Innovation Fund(POC-012)+3 种基金the János Bolyai Research Scholarship of the Hungarian Academy of Sciences(G.T.and F.K.K.)supported by the UNKP-18-4 new national excellence program of the Ministry of Human Capacities(G.T.and F.K.K.)by the EU and co-financed by the European Regional Development Fund under the project GINOP-2.3.2-15-2016-00008Richárd Botár and Eniko Madarasi were also supported by the Doctoral School of Chemistry at the University of Debrecen,Debrecen,Hungary.
文摘A new potential Zn^(Ⅱ)responsive Mn^(Ⅱ)-based MRI CA candidate derived from pyclen-3,9-diacetate(3,9-PC2A)has been synthesized and it possesses a di-(2-picolyl)amine(DPA)moiety as an active arm.The PC2A-DPA ligand was found to form a thermodynamically stable complex with Mn^(Ⅱ)(log K_(MnL)=15.87(6)which translates into a pMn of 8.79)which also possesses outstanding inertness towards Zn^(Ⅱ)ion triggered transmetallation(t_(1/2)at pH=6.0 is 64.5 h).The[Mn(PC2A-DPA)]complex has a relatively high relaxation rate(3.11 s^(−1)at 1.41 T and 37℃for a 0.96 mM complex)which is not affected by the Zn^(Ⅱ)concentration directly,yet in the co-presence of 0.7 mM human serum albumin(HSA)the relaxation rate values(both R_(1)and R_(2))increased significantly(9.08 s^(−1)at 1.41 T and 37℃,for a 0.748 mM complex)owing to the efficient binding of the complex to the protein(log K_(aff)=3.5±0.1 M−1).The increase is large enough to visualize it by MR imaging using phantoms in vitro while preliminary in vivo MRI experiments confirmed that the glucose stimulated Zn^(Ⅱ)secretion(GSZS)can be visualized in the prostate of a healthy mouse.
