1.3 Literature Survey of NiSOD Analogues
According to the protein structure of NiSOD reported by literature, some researchers started to synthesize model compounds for investigating the spectroscopy and reactivity of NiSOD. The active site structure of NiSODred is a Ni(II) square planar geometry and NiSODox is a Ni(III) square pyramidal geometry. In synthetic chemistry, Ni(II) compounds could be stablized with four or six coordination environments, depending on its ligand donating ability. Several complexes with a Ni(III) center have been reported,21-24 but structurally characterized Ni(III) complexes with a square pyramidal geometry are rare. Hence, the analogues of NiSODred were much more than that of NiSODox. Herein, we will introduce some literature survey about NiSOD analogues, including structural NiSODred mimics, structural NiSODox
mimics, and functional NiSODmodels.
1.3.1 Structural NiSODred Mimics
Because NiSODred demonstrates a N2S2 square planer coordination environment, most of structural NiSODred mimics were square planar Ni(II) complexes. Their structural and spectroscopic studies were investigated.
In 1987, Krüger and Holm reported several complexes as hydrogenase mimics (Fig. 1-7). The nickel center of these complexes was coordinated by two nitrogen atoms and two sulfur atoms with cis arrangement. With this structural similarity, these nickel compounds were used for the some further investigations of NiSODred. In addition, because of the electron rich ligand environments, the nickel center of compounds can be oxidized to higher oxidation state by the addition of oxidants.
Fig. 1-7 Ni(II)N2S2 complexes reported by Krüger and Holm.
Fig. 1-8 EPR spectra of the Ni(III)N2S2 complexes reported by Krüger and Holm.
Shearer and Hegg reported a structural NiSODred mimic with a similar N2S2
ligand skeleton in 2010 and provided insight into the consequences of the different coordination environments on the properties of the Ni ions. They systematically examined two square-planar Ni(II)N2S2 complexes and discussed the spectroscopy and DFT results by comparing with the active center of NiSODred.25
Fig. 1-9 Structural NiSODred mimic by Sheare and Hegg and co-workers.
In 2008, Jensen and co-workers synthesized several pentadentate nickel(II) complexes, they prepared hydrotris(3-phenyl-5-methylpyrazoyl)- boratonickel(II) complexes with organoxanthate or dithiocarbamate coligands equilibrate between κ2- and κ3-chelation modes of the scorpionate ligand in solution, connecting N2S2 square-planar and N3S2 pyramidal ligand fields and a spin crossover. The complexes also exhibit quasi-reversible oxidations at low anodic potentials, thus modeling the structure, dynamics, and redox reactivity of the reduced NiSOD active site.26
Fig. 1-10 Structural NiSODred mimics by Jesen and co-workers.
Moreover, Harrop reported several mimics, one of those mimics was synthesized by N3S2 ligand by modified from a N2S2 ligand, forming a square planar Ni(II) complex with an axial position pyrindinyl group. The structural and electoral property of this mimic is quite similar to that of NiSODred. However, oxidation of this complex provides a disulfide-linked dinuclear species, which is due to the formation of thiyl
radical during the redox process. The EPR spectrum revealed an isotropic signal at g
= 2.00 that likely originates from an S-based (thiyl) radical. Also an anisotropic signal with a large g spread (g = [2.26, 2.17, 2.00]) is observed, indicating a Ni(III) species.
Simulation of this data suggests that it is likely coincidental with the S-radical signal and the five coordinate Ni(III) intermediate can not be isolated.27
Fig. 1-11 Structural NiSODred mimics by Harrop and co-workers.
1.3.2 Structural NiSODox Mimics
In 1998, Hanss and Krüger found a nearly axial signal in EPR by adding excess pyridine to [Ni(phmi)]-, which is one of the series complexes published by Krüger and Holm in 1987. The splitting of the gz component due to super-hyperfine coupling of a
complex [Ni(emi)]- was also been reported.
Fig. 1-12 EPR specrum of structural NiSODox mimics by adding excess pyridine.
In 2010, a square pyramidal [NiIIN2S2] complex was generated by electrochemical oxidation in the presence of imidazole by Duboc and co-workers, mimicking the redox structural changes of NiSOD. In addition, EPR measurements coupled to DFT calculations demonstrate that the metal character in the redox active orbital increases drastically upon imidazole binding, implicating that these geometrical modifications are crucial for the stabilization of the Ni(III) state.23b
Fig. 1-13 Structural NiSODox mimic by Duboc and co-workers.
made it possible to oxidize the nickel center from Ni(II) to Ni(III), and the Ni(III) EPR signal was demonstrated. However, these salen-type or N2S2 nickel complexes could not execute the reactivity of superoxide disproportionation.
1.3.3 Functional Models of NiSOD
In functional models of NiSOD study, several model systems employed peptides maquettes, and some low-MW coordination complexes have been constructed. The first peptide analogue was synthesized by Shearer and co-workers, several derivatives were also constructed with electronically modification of the axial position histidine (Fig. 1-14).28
Fig. 1-14 Structures of the NiSOD maquette models based on [Ni(SODM1)] [SODM1 = H′CDLPCGVYDPA, where H′ = H (1), Me (1MeIm), 2,4-dinitrophenyl (1DNP), and tosyl (1Tos)].
On the other hand, the first low-MW NiSOD model complex that demonstrated reactivity toward superoxide radical was synthesized by Darensbourg and co-workers in 2009.29 The superoxide reactivity of these complexes was investigated by the nitroblue tetrazolium assay. This qualitative test based on the reduction of NBT by
NiSOD provide O2− stability to the coordination unit, however, this complex could not stable with the addition of H2O2. Besides, The exact role of the nickel center in the SOD chemistry was not defined.
Fig. 1-15 Functional NiSODred model by Darensbourg and co-workers.
Fig. 1-16 Nitroblue tetrazolium (NBT) reaction with superoxide to produce formazan.
In 2010, Laurence and co-workers synthesized a model shown that the coordination sphere of Ni-SOD can be mimicked using the tripeptide asparagine- cysteine-cysteine (NCC).31 A standard SOD activity assay using xanthine oxidase was performed,32 showing that Ni-NCC does exhibit SOD activity, but it is slower than NiSOD. The IC50 for Ni-NCC (4.1 × 10-5 M) is comparable to those values reported for other peptide mimics, particularly the maquette with bis-amide nitrogen coordination (3 × 10-5 M).33
Fig. 1-17 The proposed coordination in Ni-NCC.
The first five-coordinate analogue of NiSODox was described in 2012 by our group utilizing an N3O2 ligand. Because of the steric restrictions imposed by the ligand frame, the pyridine-N was forced to occupy the axial position upon coordination to the Ni center. Regardless of the oxidation state, a clever design strategy to impose a five-coordinate geometry, a Ni(II) complex, Ni(BDPP) was formed. Chemical oxidation of Ni(BDPP) cleanly yielded the Ni(III) complex [Ni(BDPP)](PF6) that was structurally characterized by X-ray crystallography.
Furthermore, [Ni(BDPP)](PF6) was employed to react with excess KO2, O2 and Ni(BDPP) in stoichiometric yields occured. Unfortunately, Ni(BDPP) did not react with KO2 to produce H2O2. It appears that careful construction of the ligand frame to house five-coordinate and low-spin Ni(II) could be an additional requirement for a functional NiSOD model.22e
Fig. 1-18 Functional NiSODox model by Lee and co-workers.
(Left: Ni(BDPP), Right: [Ni(BDPP)](PF6))
In this study, we design and synthesize several complexes based on Ni(BDPP) skeleton for the superoxide reactivity improvement and the ligand alterability. These complexes could provide us the opportunities to compare the differences of the coordination numbers and electronic environments of the nickel complexes with Ni(BDPP). Furthermore, we could oxidize these Ni(II) complexes to Ni(III) species and then investigate their reactivity towards superoxide, and gain insight into the role of structure and reactivity with the active center of NiSOD.
CHAPTER TWO: EXPERIMENTAL SECTION
2.1 Synthetic Materials and Methods
Unless otherwise noted, all manipulations were carried out at room temperature under an atmosphere of dinitrogen in a mBRAUN glove box (N2(g)-filled glove box maintained at or below 0.1 ppm of O2 and 1 ppm of H2O) or using high-vacuum Schlenk techniques. Dichloromethane (DCM), acetonitrile (ACN), hexanes, and diethyl ether were dried over mBRAUN solvent purification system (MB-SPS-Compact), and purged with dinitrogen prior to use. Tetrahydrofuran (THF) and pentane were distilled from sodium/benzophenone ketyl. Sodium hydride (60 % in mineral oil) was washed with hexanes and dried by the vacuum, stored in the glove box. [Ni(CH3CN)6](ClO4)2 was synthesized from Ni(ClO4)2·6H2O, washed by ACN for three times and crystallized by the slow diffusion method of diethyl ether.
Geduran® Silica gel 60 (EMD Millipore) was used for column chromatograph.
Analytical thin layer chromatography was performed by using silica gel 60 GF254 (EMD Millipore). All other reagents and solvents were purchased from chemical suppliers and used as received. 2,6-Bis(bromomethyl)pyridine, N-benzylbis(3-bromopropyl)amine, (S)-2-(diphenylhydroxymethyl)pyrrolidine, and 1,1’-dibromoferrocene were prepared by following the literature procedures.34-37
NMR spectra were recorded on Bruker AVANCE 400 NMR as noted. Chemical shifts were reported in ppm and referenced to residual protonated solvent; coupling
EC-V160 as noted. Single crystals were characterized by the Bruker Enraf-Nonius Kappa CCD Single-Crystal Diffractometer and Bruker Kappa Apex II Single-Crystal Diffractometer at the NSC Regional Instrumental Center at Nation Taiwan Normal University, Taipei, Taiwan. Elemental Analyses were performed on Heraeus varioIII-NCH Analyzer at the NSC Regional Instrumental Center at Nation Taiwan University, Taipei, Taiwan. EPR measurements were performed at X-band using a Bruker E580 spectrometer equipped with a Bruker ELEXSYS super high sensitivity cavity at the NSC Regional Instrumental Center at Nation Tsing Hua University, Hsinchu, Taiwan.
2.2 Synthesis and Characterization of Ligands and Complexes 2.2.1 Synthesis and Characterization of H2BDPMeP
i) 2,6-Bis(bromomethyl)pyridine
48 wt% HBr (100 mL) was gently added to 2,6-pyridinedimethanol (5.00 g, 35.9 mmol), refluxed for 5 h and then cooled to room temperature. The reaction solution was quenched and neutralized by adding NaOH(aq) (1 M). The resulting aqueous solution was extracted by DCM. The organic layers were combined and extracted with saturated NaCl(aq), dried over anhydrous MgSO4. The solution was evaporated under vacuum, and the residue was purified by flash column chromatography with the DCM as eluent to yield 2,6-bis(bromomethyl)pyridine (4.28 g, 46%) as a white solid.
1H NMR (400MHz, CDCl3): δ 7.70 (t, 1H, Ph), 7.38 (d, 2H, Ph), 4.54 (s, 4H, CH2).
See Appendix A-1.
ii) (S)-Ν-Ethoxycarbonylproline methyl ester
K2CO3, EtOH
Ethyl chloroformate (17.54 mL, 184.31 mmol) was added dropwisely to a methanol solution of L-proline (7.00 g, 60.80 mmol) and K2CO3 (16.80 g, 121.55 mmol) under ice-bath and reacted for 16 h. After the reaction was completed, the reaction solution was evaporated under vacuum to form a white solid residue, which was dissolved in DCM and washed with water. The DCM solution was then dried
(S)-Ν-Ethoxycarbonylproline methyl ester (8.0488 g, 40.0 mmol) was dissolved in dried THF under nitrogen atmosphere and 120 mL of 1 M 4-methyl-phenylmagnesium bromide (120.0 mmol) was dropwisely added to the reaction solution at 0 °C. After 2 h, the solution was quenched by saturated NH4Cl(aq)
to see the color of the solution changed from black to white. The reaction solution was evaporated under vacuum to form a white residue. The residue was dissolved in ethyl acetate and washed with water for 3 times. The organic layer was dried over
anhydrous MgSO4, and concentrated under reduced pressure. Purification of the
A solution of (S)-2-(Bis(4-methylphenyl)hydroxymethyl)-N-ethoxycarbonyl- pyrrolidine (13.7514 g, 38.9 mmol) and KOH (65.4900 g, 1167.0 mmol) was refluxed in ethanol (200 mL) for 2 days. The solution was evaporated under vacuum to form a white solid residue, which was dissolved in DCM and washed with water. The DCM solution was then dried over anhydrous MgSO4, and concentrated under reduced pressure. A white powder was obtained in 83% yield (9.0988 g). 1H NMR (400MHz, CDCl3): δ 7.44 (d, 2H, Ph), 7.36 (d, 2H, Ph), 7.08 (t, 4H, Ph), 4.21 (t, 1H, CH), 3.72 (t,
v) 2,6-Bis(((S)-2-(bis(4-methylphenyl)hydroxymethyl)-1-pyrrolidinyl)methyl)- pyridine (H2BDPMeP)
A solution of (S)-2-(bis(4-methylphenyl)hydroxymethyl)pyrrolidine (2.8118 g, 10.0 mmol), 2,6-bis(bromomethyl)pyridine (1.3150 g, 5.0 mmol), and K2CO3 (1.3812 g, 10.0 mmol) was refluxed in ethanol (200 mL) for 3 days. The solution was 125.5, 120.3, 77.8, 70.6, 61.8, 55.5, 29.7, 24.3, 20.9, 20.8. See Appendix A-5, 6. Anal.
Calcd for C45H51N3O2: C, 81.16; H, 7.72; N, 6.31. Found: C, 80.698; H, 7.847; N,
2.2.2 Synthesis and Characterization of Ni(BDPMeP) (1)
ACN (30 mL) was added to a mixture of H2BDPMeP (0.1330 g, 0.2 mmol), NaH (0.0012 g, 0.5 mmol) and [Ni(CH3CN)6](ClO4)2 (0.1008 g, 0.2 mmol) in a 100-mL Schlenk flask. The reaction solution was stirred at room temperature overnight, and a green precipitate was formed. The upper solution was removed by cannula, and the precipitate was dissolved in 5 mL of DCM. The DCM solution was washed with hexanes (3 × 30 mL) to precipitate the green powder, which was dissolved in 5 mL DCM for recrystallization by slow diffusion (DCM/pentane) at room temperature.
Green crystals of NiBDPMeP (1) were obtained over one day in 58% yield (0.0837 g).
UV-vis (DCM): λmax (ε, M−1 cm−1) 360 (900), 700 (20) nm, 1090 (30). Anal. Calcd for C45H49N3NiO2·0.5 THF: C, 74.41; H, 7.04; N, 5.54. Found: C, 74.07; H, 6.62; N, 5.83.
Ni N N
N O
O
2.2.3 Synthesis and Characterization of [Ni(HBDPMeP)](ClO4)·(CH2Cl2)2 (2)
ACN (30 mL) was added to a mixture of H2BDPMeP (0.1330 g, 0.2 mmol), NaH (0.0048 g, 0.2 mmol) and [Ni(CH3CN)6](ClO4)2 (0.1008 g, 0.2 mmol) in a Schlenk flask. The reaction solution was stirred at room temperature overnight. The solvent of the resulting solution was removed under vacuum to afford a red solid residue, which was dissolved in 7 mL THF. The THFsolution was washed with diethyl ether (3 × 35 mL) to precipitate a red powder. The red powder was dissolved in 10 mL THF for recrystallization by slow diffusion (THF/diethyl ether) at room temperature.
Crystals of [NiHBDPMeP](ClO4)·(CH2Cl2)2 (2) was obtained over three days in 66%
yield (0.1306 g). UV-vis (DCM): λmax (ε, M−1 cm−1) 340 (2130), 480 (200) nm. Anal.
Calcd for C45H50ClN3NiO6·2.0 CH2Cl2: C, 56.85; H, 5.48; N, 4.23. Found: C, 57.52;
H, 5.88; N, 4.45.
N NiN N
O HO
2.2.4 Synthesis and Characterization of H2BDPPA
i) N-benzylbis(3-hydroxylpropyl)amine
A mixture of aniline (1.8626 g, 20 mmol), 3-chloro-1-propanol (6.615 g, 70 mmol), and calcium carbonate (4.0032 g, 40 mmol) was refluxed in H2O for 24 h, and the reaction solution was alkalified by NaOH(aq) (2 M) to pH = 10 at 0 °C. The resulting solution was extracted by DCM for 3 times, and the organic layers were combined and dried over anhydrous MgSO4 to obtain yellow oil product in 90% yield (3.7752 g). 1H NMR (400MHz, CDCl3): δ 7.23 (t, 2H, Ph), 6.77 (dd, 3H, Ph), 3.73 (t, 4H, CH2), 3.43 (t, 4H, CH2), 1.83 (t, 4H, CH2). See Appendix A-7.
ii) N-benzylbis(3-bromopropyl)amine
N-benzylbis(3-hydroxylpropyl)amine (1.4 g, 6.4 mmol) was added to concentrated 48 wt% HBr (24 mL), and the mixture was refluxed for 36 h. When the
NH2
CaCO3
N OH
HO
+ Cl OH
H2O
2 times and brine for 1 time. The organic and which was dried over anhydrous MgSO4 to obtain brown oil product in 82% yield (1.611g). 1H NMR (400MHz, CDCl3): δ 7.23 (d, 2H, Ph), 6.74 (d, 3H, Ph), 3.48 (m, 8H, CH2), 2.14 (t, 4H, CH2).
See Appendix A-8.
iii) (S)-2-(Diphenylhydroxymethyl)-N-ethoxycarbonylpyrrolidine
(S)-Ν-Ethoxycarbonylproline methyl ester (2.012 g, 10.0 mmol) was dissolved in dried THF under nitrogen atmosphere. Phenylmagnesium bromide (1 M, 40.0 mL) was dropwisely added to the reaction solution at 0 °C. After 2 h, the solution was quenched by saturated NH4Cl(aq) and the color of the solution changed from black to white. The resulting solution was evaporated under vacuum to form a white residue.
The residue was dissolved in ethyl acetate and washed with water for 3 times. The organic layer was dried over anhydrous MgSO4, and concentrated under reduced pressure. Clear crystals of (S)-2-(Diphenylhydroxymethyl)-N-ethoxycarbonyl- pyrrolidine were obtained from the recrystallization in ethyl acetate in 80% yield
iv) (S)-2-(Diphenylhydroxymethyl)pyrrolidine
A solution of (S)-2-(Diphenylhydroxymethyl)-N-ethoxycarbonylpyrrolidine (1.4815 g, 4.6 mmol) and KOH (7.7432 g, 138.0 mmol) was refluxed in ethanol (100 mL) for 2 days. The solution was evaporated under vacuum to form a white residue, which was dissolved in DCM and washed with water. The DCM solution was then dried over anhydrous MgSO4, and concentrated under reduced pressure. The white powder of (S)-2-(Diphenylhydroxymethyl)pyrrolidine was obtained in 95% yield (1.108 g). 1H NMR (400MHz, CDCl3): δ 7.65 (dd, 4H, Ph), 7.36 (d, 4H, Ph), 7.24 (s, 2H, Ph), 4.31 (s, 1H, CH), 2.98 (t, 2H, CH2), 1.68 (m, 4H, CH2). See Appendix A-10.
v) (S, S)-bis[2-(diphenylmethanol)pyrrolidine]dipropylaniline (H2BDPPA)
A solution of (S)-α, α-diphenyl-2-pyrrolidinemethanol (1.8455 g, 6.01 mmol), N-benzylbis(3-bromopropyl)amine (3.0456 g, 12.02 mmol), and K2CO3 (1.6613 g, 6.02 mmol) was refluxed in ACN (50 mL) for 3 days. The solution was evaporated
KOH EtOH
HN OH N
O OEt
OH
concentrated under reduced pressure. Purification by flash column chromatography afforded colorless oil which was recrystallized in ethyl acetate. Colorless crystals of H2BDPPA were obtained in 43% yield (1.7659 g). 1H NMR (400MHz, CDCl3): δ 7.64 (d, 4H, Ph), 7.56 (d, 4H, Ph), 7.30 (q, 8H, Ph), 7.17 (m, 6H, Ph), 6.65 (t, 1H, Ph), 6.32(d, 2H, Ph), 4.75 (s, 2H, CH2), 3.81 (dd, 2H, OH), 3.23 (m, 2H, CH), 2.79 (m, 2H, CH2), 2.58 (m, 2H, CH2), 2.40 (m, 2H, CH2), 2.09 (m, 2H, CH2), 1.90 (m, 4H, CH2) 1.72 (m, 6H, CH2), 1.41 (m, 4H, CH2); 13C NMR (400MHz, CDCl3): δ 148.1, 147.5, 146.3, 129.0, 128.1, 126.2, 125.6, 115.3, 111.6, 77.7, 71.2, 64.3, 55.3, 53.9, 48.3, 46.6, 46.2, 29.4, 26.2, 26.0, 25.4, 24.4, 11.5. See Appendix A-11, 12. Anal. Calcd for C46H53N3O2: C, 81.26; H, 7.86; N, 6.18. Found: C, 81.32; H, 7.86; N, 6.22.
2.2.5 Synthesis and Characterization of Ni2(BDPPA)2 (3)
ACN (30 mL) was added to a mixture of H2BDPPA (0.3400 g, 0.5 mmol), NaH (0.0300 g, 1.25 mmol) and [Ni(CH3CN)6](ClO4)2 (0.2520 g, 0.5 mmol) in a Schlenk flask. The reaction solution was stirred at room temperature overnight. The solvent of the resulting solution was removed under vacuum to afford a red residue, which was dissolved in 10 mL of DCM. The DCMsolution was washed with of hexanes (3 × 50 mL) to precipitate the red powder, which was dissolved in 7 mL DCM. Single crystals were obtained by layering the DCM solution of 3 with hexane at room temperature over two days in 31% yield (0.1195 g). UV-vis (DCM): λmax (ε, M−1 cm−1) 490 (160), 650 (25) nm. Anal. Calcd for C92H102N6Ni2O4·0.5CH2Cl2: C, 73.30; H, 6.85; N, 5.54.
Found: C, 73.44; H, 6.95; N, 5.51.
2.2.6 Synthesis and Characterization of 1,1’-Dibromoferrocene (FcBr2)
Hexanes (30 mL) was added to a mixture of ferrocene (5.58g, 30.00 mmol) and TMEDA (10.5 mL, 69.9- mmol) in a 150-mL three-necked flask equipped with a pressure-equalizing dropping funnel. nBuLi (2.5 M in hex, 25.5 mL, 63.75 mmol) was added to the solution dropwisely at 0 °C. After nBuLi was completely added, the temperature of the solution was slowly raised to room temperature and the reaction solution was stirred overnight. Orange solid was suspended in the resulting brown solution, which was washed with hexanes (3 × 30). The resulting solution was evaporated under vacuum to afford an orange solid. Diethyl ether (90 mL) was added to the orange solid to form a suspension solution, which was cooled down to –70 °C.
1,1,2,2-tetrabromoethane (6.5 mL, 55.90 mmol) dissolved in diethyl ether (30 mL) was dropwisely added to the suspension solution with vigorous stirring. The temperature of the reaction solution was gradually raised to room temperature, and the solution was stirred overnight. The top dark-brown layer was decanted, and quenched with water (15 mL) and provided a dark brown solid after solvent removal. The residue was extracted by hexanes (15 mL) to form a suspension. The suspension was filtered through celite. The filtrate was washed by a saturated aqueous solution of
was dried over MgSO4. The orange crystals of FcBr2 were obtained from the recrystallization in hexanes in 8% yield (0.8485 g). 1H NMR (400MHz, CDCl3): δ 4.42 (s, 4H, Ph), 4.17 (d, 4H, Ph). See Appendix A-13.
2.2.7 Synthesis and Characterization of [FcBr2](BF4)
2,3-Dihloro-5,6-dicyano-1,4-benzoquinone (DDQ, 0.1135 g, 0.5 mmol) was added to 1,1’-dibromoferrocene (0.3418 g, 1.0 mmol) in diethyl ether (20 mL) at room temperature, and the reaction mixture was stirred for 10 mins. Then, HBF4 (32.5 wt% solution in H2O, 2 mmol) was added at 0 °C. A dark blue solid formed immediately, which was washed by cold diethyl ether until the solution became colorless. The solvent of the resulting solution was evaporated under vacuum to give a dark blue product. Anal. Calcd for C92H102N6Ni2O4: C, 27.89; H, 1.87; N, 0.00.
Found: C, 28.09; H, 1.86; N, 0.11.
2.2.8 Synthesis and Characterization of [NiIII(BDPMeP)](BF4) (4)
ACN (15 mL) was added to a mixture of Ni(BDPMeP) (0.0723 g, 0.1 mmol) and
cm−1) 300 (6090), 375 (7020), 455 (3160) nm. Anal. Calcd for C45H49BF4N3NiO2·1.0 CH2Cl2: C, 61.78; H, 5.75; N, 4.70. Found: C, 64.04; H, 5.81; N, 5.09.
2.2.9 Synthesis and Characterization of NiIII2(BDPPA)2(BF4)2 (5)
THF (5 mL) was added to a mixture of Ni2(BDPPA)2 (0.0155 g, 0.01 mmol) and [FcBr2](BF4) (0.0086 g, 0.02 mmol) in a Schlenk flask at –40 °C. After 30 min, the reaction solution turned to dark purple color, which was washed by of diethyl ether (3
× 15 mL) to form a dark purple precipitate of NiIII2(BDPPA)2(BF4)2. UV-vis (THF):
λmax (ε, M−1 cm−1) 300 (11035), 335 (5200), 570 (3255) nm.
2.3 Reaction of NiIII-complexes with KO2
2.3.1 [NiIII(BDPMeP)](BF4) (4)
i) Detection by UV-vis spectroscopy
The reaction was performed by adding 3 mL ACN solution of [NiIII(BDPMeP)](BF4)(4) (1.5 × 10-4 M) to a solid of KO2 (0.0053 g, 50 equiv.) in a UV-vis cell. The reaction was detected by a UV-vis spectro meter.
ii) Detection by GC
In order to detect the production of O2(g) from the reaction of 4 and KO2, two vials, each was filled control and sample experiments, were prepared. First, two vacuum vials, which contained with KO2 (0.0711 g, 1.00 mmol), 17 mL N2(g) and 1 mL ACN. In the sample experiment, 2 mL of [NiIII(BDPMeP)](BF4) (4) (0.0405 g, 0.05 mmol) ACN solution was added to the vial mentioned above. In the control experiment, 2 mL ACN was added to the other vial. Both solutions were stirred vigorously. The color of the sample experiment changed from brown to green. The containing O2(g) in both vials was detected by the Milli-Whistle GC38. The produced amount of O2(g) was calculated for comparison with the ideal produced amount of O2(g). The yield of the produced O2(g) is 92%.
2.3.2 NiIII2(BDPPA)2(BF4)2 (5)
NiIII2(BDPPA)2(BF4)2 (5) (1.0 × 10-3 M) to a solid of KO2 (0.0053 g, 50 equiv.) in a UV-vis cell. The reaction was detected by a UV-vis spectro meter.
ii) Detection by GC
In order to detect the production of O2(g) from the reaction of 5 and KO2, two vials, each was filled control and sample experiments, were prepared. First, two vacuum vials, which contained with KO2 (0.0711 g, 1.00 mmol), 17 mL N2(g) and 0.4 mL THF. In the sample experiment, 2 mL of NiIII2(BDPPA)2(BF4)2 (5) (0.0156 g, 0.010 mmol) THF solution was added to the vial mentioned above. In the control experiment, 2 mL THF was added to the other vial. Both solutions were stirred vigorously. The color of the sample experiment changed from brown to green. The containing O2(g) in both vials was detected by the Milli-Whistle GC. The produced amount of O2(g) was calculated for comparison with the ideal produced amount of O2(g). The yield of the produced O2(g) is 82%.
CHAPTER THREE: RESULTS AND DISCUSSION
NiSOD is an enzyme, which is capable to catalyze the dismutation of O2− into O2
and H2O2 through a cycle of NiII and NiIII oxidation states. In order to mimic the function of NiSOD, a functional model [Ni(H2BDPP)(CH3CN)](BF4)2 was synthesized by Lee and co-workers. [Ni(H2BDPP)(CH3CN)](BF4)2 could be oxidized to a nickel(III) species by the addition of KO2, and O2- could be reduced to H2O2
through a hydrogen atom abstraction. In addition, the nickel(III) species [NiIII(BDPP)](PF6) is able to promote the oxidation of O2- into O2, through the redction of NiIII to NiII.22e As far as we know, only peptide models such as Ni(SODM1) and Ni(SODM2),39 reported by Shearer and Ni-GGNCC and Ni-NCC,31 reported by Laurence have demonstrated the function of NiSOD. Therefore, [Ni(H2BDPP)(CH3CN)](BF4)2 is the first model which possesses the function of NiSOD.
However, as a enzyme model, [Ni(H2BDPP)(CH3CN)](BF4)2 still remains some weakness. For example, the structure of [Ni(H2BDPP)(CH3CN)](BF4)2 is different to the coordination sphere of the active site of NiSOD and the geometry translation of [Ni(H2BDPP)(CH3CN)](BF4)2 in the catalytic cycle also showed the difference with NiSOD. Reduced form of NiSOD (NiSODred) contains a square planar NiII geometry
However, as a enzyme model, [Ni(H2BDPP)(CH3CN)](BF4)2 still remains some weakness. For example, the structure of [Ni(H2BDPP)(CH3CN)](BF4)2 is different to the coordination sphere of the active site of NiSOD and the geometry translation of [Ni(H2BDPP)(CH3CN)](BF4)2 in the catalytic cycle also showed the difference with NiSOD. Reduced form of NiSOD (NiSODred) contains a square planar NiII geometry