Supporting Information for
Water Soluble Chiral Metallopeptoids
Maria Baskin and Galia Maayan
Schulich Faculty of Chemistry, Technion- Israel Institute of Technology, Haifa, Israel, 32000
Materials:
Rink Amide resin was purchased from Novabiochem; (S)-(+)-1-methoxy-2-propylamine
(Nsmp) and Trifluoroacetic acid (TFA) were purchased from Alfa Aesar; 8-hydroxy-2quinolinecarbonitrile was purchased from Acros; Bromoacetic acid, cobalt acetate
tetrahydrate and copper acetate monohydrate were purchased from MERCK;
N,N’diisopropylcarbodiimide (DIC), piperidine, acetonitrile (ACN) and water HPLC
grade solvents were purchased from Sigma-Aldrich; dimethylforamide (DMF) and
dichloromethane (DCM) solvents were purchased from Bio-Lab Itd. These reagents and
solvents were used without additional purification, with the exception of DMF that was
dried with molecular sieves.
Instrumentation:
Peptoid oligomers were analyzed by reversed-phase HPLC (analytical C18(2) column,
Phenomenex, Luna 5µm, 100 Å, 2.0x50 mm) on a Jasco UV-2075 PLUS detector. A
linear gradient of 5–95% ACN in water (0.1% TFA) over 10 min was used at a flow rate
of 700 L/min. Preparative HPLC was performed using a AXIA Packed C18(2) column
(Phenomenex, Luna 15m, 100 Å, 21.20x100mm). Peaks were eluted with a linear
gradient of 5–95% ACN in water (0.1% TFA) over 50 min at a flow rate of 5 mL/min.
Mass spectrometry of peptoid oligomers was performed on a Advion expression CMS
mass spectrometer under electrospray ionization (ESI), direct probe ACN:H2O (95:5),
flow rate 0.2 ml/min. Mass spectrometry of metal complexes was performed on a Waters
LCT Premier mass spectrometer under electrospray ionization (ESI), direct probe
ACN:H2O (70:30), flow rate 0.3 ml/min. UV measurements were performed using an
Agilent Cary 60 UV-Vis spectrophotometer, a double beam, Czerny-Turner
monochromator. CD measurements were performed using a circular dichroism
spectrometer Model Jasco 810 Spectropolarimeter with linearity of the Abs response up
to 4 AU. EPR spectra were recorded on a Bruker EMX-10/12 X-band (ν=9.4 GHz)
digital EPR Spectrometer. Spectra processing and simulation were performed with
Bruker WIN-EPR and SimFonia Software. Data processing was done with the softwares
Excel and KaleidaGraph.
Table S1. Peptoid oligomer sequences and their isolated metal complexes.
Nhq = 8-hydroxy-2-quinolinemethylamine, Nsmp = (S)-(+)-1-methoxy-2-propylamine.
Molecular weight
Peptoid and Peptoid -Metal complex
Calc.: Found (gr/mol)
Nsmp-Nhq-Nsmp-Nsmp-Nhq-Nsmp-Nsmp (7mer-HQ2)
1091.3 : 1092.2
7mer-HQ2Co
1148.19 : 1147.49
7mer-HQ2Cu
1152.80 : 1151.49
Nsmp-Nhq-Nsmp-Nsmp-Nhq-Nsmp-Nhq-Nsmp-NsmpNhq-Nsmp-Nsmp (12mer-HQ4)
12mer-HQ4(Co)2
1907.2 : 1907.2
12mer-HQ4(Cu)2
2030.26 : 2030.88
2021.03 : 2020.89
Table S2. EPR parameters of the Cu(II) complexes.
12mer-HQ4(Cu)2
7mer-HQ2Cu
(HQ2Cu1, 2 HQ)2C
𝑨∥ [× 𝟏𝟎−𝟒 𝒄𝒎−𝟏 ]
157.6
163.8
162
𝑨∥ [𝑮]
𝒈⊥
150
2.086
157
2.080
160
2.042
𝒈∥
2.250
2.235
2.172
𝒈∥ /𝑨∥
143
137
134
Table S3. UV-Vis absorbance data of peptoid oligomer sequences and their metal
complexes. Nspe =(S)-(-)-1-phenylethylamine, Nhq = 8-hydroxy-2
quinolinemethylamine.
Compound
First maximum
Second maximum
λ, nm
ε, M-1cm-1
λ, nm
ε, M-1cm-1
Nsmp-Nhq-Nsmp-Nsmp-Nhq-NsmpNsmp (7mer-HQ2)
7mer-HQ2Co
244
58700 ± 50
309
3900 ± 50
261
42200 ± 50
370
3100 ± 30
7mer-HQ2Cu
261
52600 ± 50
372
2950 ± 10
Nsmp-Nhq-Nsmp-Nsmp-Nhq-NsmpNhq-Nsmp-Nsmp-Nhq-Nsmp-Nsmp
(12mer-HQ4)
12mer-HQ4(Co)2
244
134800 ± 50
307
10400 ± 50
261
84700 ± 50
375
9200 ± 50
12mer-HQ4(Cu)2
263
115900 ± 50
379
7900 ± 40
Synthetic procedure for Nhq:
Nhq = 8-hydroxy-2-quinolinemethylamine is synthesized by reduction of 8hydroxyquinoline carbonitrile with molecular hydrogen using palladium on carbon as a
catalyst according to previously published procedure.3
Scheme 1: Synthetic routs to Nhq.
References:
1. Sakaguchi, U., Addison, A. W., J. Chem. Soc., Dalton Trans., 1979, 600-608.
2. Gersmann, H. R., J. D. Swalen, J. Chem. Phys, 1962, 36, 3221-3233.
3. Maayan, G.; Yoo, B., Kirshenbaum, K. Tetrahedron Letters, 2008, 49 (2), 335-338.
Synthesis of metal complexes
Complex of 7mer-HQ2 with Co2+. To a solution of 7mer-HQ2 (2 mg, 0.002 mmol) in
water (0.25 ml), Co2+ acetate (1 mg, 0.004 mmol) was added and the mixture was stirred
for 2 hours. A pale orange solid precipitated after the addition of NH4PF6 (0.02 ml of a 1
M aqueous solution). The precipitate was isolated by centrifugation, washed twice with
water and lyophilized overnight (0.67 mg, 32% yield).
Complex of 7mer-HQ2 with Cu2+. To a solution of 7mer-HQ2 (2 mg, 0.002 mmol) in
water (0.25 ml), Cu2+ acetate (0.5 mg, 0.0025 mmol) was added and the mixture was
stirred for 2 hours. A pale green solid precipitated after the addition of NH 4PF6 (0.02 ml
of a 1 M aqueous solution). The precipitate was isolated by centrifugation, washed twice
with water and lyophilized overnight (0.71 mg, 34% yield).
Complex of 12mer-HQ4 with Co2+. To a solution of 12mer-HQ4 (2 mg, 0.001 mmol)
in water (0.25 ml), Co2+ acetate (1.1 mg, 0.0045 mmol) was added and the mixture was
stirred for 2 hours. A pale orange solid precipitated after the addition of NH4PF6 (0.02 ml
of a 1 M aqueous solution). The precipitate was isolated by centrifugation, washed twice
with water and lyophilized overnight (0.84 mg, 40% yield).
Complex of 12mer-HQ4 with Cu2+. To a solution of 7mer-HQ2 (2 mg, 0.001 mmol) in
water (0.25 ml), Cu2+ acetate (0.5 mg, 0.0025 mmol) was added and the mixture was
stirred for 2 hours. A pale green solid precipitated after the addition of NH 4PF6 (0.02 ml
of a 1 M aqueous solution). The precipitate was isolated by centrifugation, washed twice
with water and lyophilized overnight (0.83 mg, 40% yield).
HPLC
Intensity [µV]
1000000
MB7- 22min - CH1
500000
0
2.0
4.0
6.0
8.0
10.0
Retention Time [min]
12.0
14.0
Figure S1. HPLC traces of purified peptoid oligomer 12mer-HQ4 at 214nm.
7 HQ2 dry - CH1
600000
Intensity [µV]
400000
200000
0
2.0
4.0
6.0
8.0
10.0
Retention Time [min]
12.0
14.0
Figure S2. HPLC traces of purified peptoid oligomer 7mer-HQ2 at 214nm.
ESI-MS
Figure S3. MS traces of peptoid oligomer 7mer-HQ2.
Figure S4. MS traces of peptoid oligomer 12mer-HQ4.
Figure S5. MS traces of peptoid oligomer 7mer-HQ2Co complex.
Figure S6. MS traces of peptoid oligomer 7mer-HQ2Cu complex.
Figure S7. MS traces of peptoid oligomer 12mer-HQ4(Co)2 complex.
Figure S8. Expended MS traces of peptoid oligomer 12mer-HQ4(Co)2 complex.
Figure S9. MS traces of peptoid oligomer 12mer-HQ4(Cu)2 complex.
Figure S10. Expended MS traces of peptoid oligomer 12mer-HQ4(Cu)2 complex.
UV-Vis titrations
HQ4 2.5mM 10uL
HQ4 +5mM Co(ii) 2uL
HQ4+5mM Co(ii) 4uL
HQ4+5mM Co(ii) 6uL
HQ4 +5mM Co(ii) 8uL
HQ4+5mM Co(ii) 10uL
HQ4+5mM Co(ii) 12uL
HQ4 +5mM Co(ii) 14uL
HQ4+5mM Co(ii) 16uL
HQ4 +5mM Co(ii) 18uL
HQ4+5mM Co(ii) 20uL
HQ4 +5mM Co(ii) 25uL
HQ4+5mM Co(ii) 30uL
HQ4+5mM Co(ii) 40uL
HQ4+5mM Co(ii) 50uL
HQ4 +5mM Co(ii) 60uL
HQ4 +5mM Co(ii) 70uL
HQ4 +5mM Co(ii) 80uL
1.2
1
Abs
0.8
0.6
0.4
0.2
0
200
300
400
500
600
λ (nm)
Figure S11. UV-Vis spectra of 12mer-HQ4 and the formation of 12mer-HQ4(Co)2
complex, recorded at room temperature, in H2O solution. Initial concentration of 12merHQ4 was 8.5 µM.
1.2
HQ2 5mM 10uL
HQ2+Co(ii) 5mM 2uL
HQ2+Co(ii) 5mM 4uL
HQ2+Co(ii) 5mM 6uL
HQ2+Co(ii) 5mM 8uL
HQ2+Co(ii) 5mM 10uL
HQ2+Co(ii) 5mM 15uL
HQ2+Co(ii) 5mM 20uL
HQ2+Co(ii) 5mM 25uL
HQ2+Co(ii) 5mM 30uL
HQ2+Co(ii) 5mM 40uL
HQ2+Co(ii) 5mM 50uL
HQ2+Co(ii) 5mM 60uL
HQ2+Co(ii) 5mM 80uL
HQ2+Co(ii) 5mM 90uL
HQ2+Co(ii) 5mM 100uL
HQ2+Co(ii) 5mM 120uL
1
Abs
0.8
0.6
0.4
0.2
0
200
300
400
500
600
λ (nm)
Figure S12. UV-Vis spectra of 7mer-HQ2 and the formation of 7mer-HQ2Co complex,
recorded at room temperature, in H2O solution. Initial concentration of 7mer-HQ2 was
17 µM.
CD
Mol Elipticity [θ]x105 (deg cm²
dmol¯¹)
3
Free peptoid 7-HQ2
Co complex
2
Cu complex
1
0
180
230
280
330
-1
-2
λ, nm
Figure S13. CD spectra of 7mer-HQ2 with Cu and Co. The spectra were recorded at
room temperature, at concentration of 10µM in MeOH/H2O 4:1.
Mol Elipticity
[θ]x105
(deg cm² dmol¯¹)
3
12-HQ4 free
peptoid
Co complex
2
Cu complex
1
0
-1
-2
180
230
280
330
λ, nm
Figure S14. CD spectra of 12mer-HQ4 with Cu+2 and Co+2. The spectra were recorded
at room temperature, at concentration of 10µM in MeOH/H2O 4:1.