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3
and loaded onto a SP Sephadex C-25 ion exchange column. Water
was used to flush the column and a purple fraction was collected
and desalted (Sephadex LH-20 column with MeOH as eluant) to
give [Co(HL7)(CO3)] (165 mg, 92%) as a purple solid, which was
used directly: 1H NMR (400 MHz, D2O) d 1.50 (br, 4H), 1.72–1.88
(m, 2H), 2.59–2.75 (m, 2H), 2.76–3.08 (m, 14H), 3.38–3.42 (m,
2H) (exchangeable NH and OH not observed). 13C NMR (100 MHz,
D2O) d 22.38 (d, JPC = 3.3 Hz), 23.12 (d, JPC = 16.0 Hz), ꢂ27–28 (br),
47.88 (s), 47.95 (s), 49.35 (s), 50.01 (s), 53.53 (s), 55.06 (s), 56.04
(s), 58.14 (s), 63.23 (s), 167.46 (s) 31P NMR (162 MHz, D2O, decou-
pled) d 22.98.
Triflic acid (3 mL) was added to cooled (0 °C) [Co(HL7)(CO3)]
(145 mg, 0.32 mmol) and the mixture was warmed to room temper-
ature and then heated at 60 °C for 2 h. Et2O was added to precipitate
the product which was triturated and washed with Et2O to give
[Co(H2L7)(OTf)2]OTf (250 mg, 95%) as a pink solid, which was used
directly: 1H NMR (400 MHz, D2O) d 1.50–1.70 (m, 2H), 1.75–1.85
(m, 2H), 1.98–2.08 (m, 2H), 2.46–2.64 (m, 4H), 2.77–2.86 (m, 1H),
2.91–2.95 (m, 1H), 3.00–3.34 (m, 10H), 3.59–3.64 (m, 1H), 3.81–
3.86 (m, 1H) (exchangeable NH and OH not observed). 13C NMR
(100 MHz, D2O) d 20.82 (d, JPC = 4.5 Hz), 23.14 (d, JPC = 16.0 Hz),
26.92 (d, JPC = 135.2 Hz), 48.58 (s), 48.71 (s), 50.07 (s), 50.22 (s),
54.03 (s), 57.45 (s), 58.97 (s), 59.21 (s), 63.42 (s), 120.15 (q,
JFC = 317.0 Hz). 31P NMR (162 MHz, D2O, decoupled) d 28.24.
3JHH = 8.8 Hz), 9.12 (d, 2H, quinoline CH, JHH = 4.4 Hz), 11.50 (m,
2H, indole NH). HRMS (FAB, +ve): m/z 832.22941/834.23030 [M]+,
calcd for CoC36H4835/37ClN7O8S: 832.23056/834.22761.
4.2.4. 1-(Chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)
carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]-5-quinolinolato
(1,4,7,10-tetraazacyclododecane-1,7-dipropane-3,30-
disulfonate)cobalt(III) [Co(L9)(4)] (9)
A
mixture of trans-[Co(py)4Cl2]NO3 (0.035 g, 0.069 mmol),
H2L9ꢁ4HCl7 (0.041 g, 0.073 mmol), and 4 (0.032 g, 0.068 mmol)
were added into a flask pre-purged with nitrogen followed by abso-
lute EtOH (10 mL) with triethylamine (0.053 g, 0.524 mmol). The
mixture was heated under nitrogen at 50 °C with stirring for 14 days
until all the suspension was of dark green color and none of the yel-
low/white five remained. The greenish precipitate of [Co(L9)(4)] (9)
(57 mg, 88%) was filtered off and washed first with cold EtOH (5 mL),
then with cold Et2O (10 mL), and dried in a vacuum desiccator: 1H
NMR (DMSO-d6, 400 MHz): d 1.07 (m, 2H, NCH2ðCH2Þ2SO3ꢀ), 1.49
(m, 2H, NCH2CH2CH2SO3ꢀ), 1.66 (m, 4H, NCH2CH2CH2SO3
,
ꢀ
CH2SO3ꢀ), 1.91 (m, 2H, CH2SO3ꢀ), 2.29 (m, 2H, NCH2ðCH2Þ2SO3ꢀ),
2.54, 2.59 (m, 4H, CH2NðCH2Þ3SO3ꢀ), 2.72 (m, 2H, HNCH2), 2.90 (m,
2H, CH2NðCH2Þ3SO3ꢀ), 2.94 (m, 2H, HNCH2), 3.11 (m, 2H,
NCH2ðCH2Þ2SO3ꢀ), 3.35, 3.61 (m, 4H, HNCH2), 3.80, 3.82 (s, 6H,
OCH3), 3.88 (m, 1H, CH2Cl), 3.95 (s, 3H, OCH3), 3.98 (m, 1H, CH2Cl),
2
A
mixture of [Co(H2L7)(OTf)2]OTf (241 mg, 0.30 mmol),
4
4.34 (m, 1H, CHCH2Cl), 4.43 (d, 1H, CONCH2, JHH = 10.7 Hz), 4.83
(t, 1H, CONCH2, JHH = 10.3 Hz), 6.21 (br s, 1H, NH), 6.97, 7.06 (s,
2
(115 mg, 0.24 mmol) and pyridine (0.3 mL) in MeOH (20 mL) was
stirred at 50 °C for three days. All volatiles were removed and the
residue was dissolved in MeOH and filtered through Celite. The fil-
trate was concentrated and purified by chromatography twice on a
Sephadex LH-20 column eluted with MeOH to give [Co(H-
L7)(4)](OTf) (7) (133 mg, 46%) as a green solid. Purity was 95% by
HPLC and the product consisted of two isomers according to its 1H
NMR. 1H NMR (400 MHz, D2O): two isomers (approximately 1:1) d
0.80–1.30 (m, 4H), 1.40–1.70 (m, 4H), 2.25–2.35 (m, 1H), 2.47–
2.56 (m, 2H), 2.66–3.00 (m, 6H), 3.05–3.45 (m, 6H), 3.52–3.76 (m,
3H), 3.83/3.85 (2s, 6H, 2MeO), 3.97/4.07 (2s, 3H, MeO), 4.08–4.19
(m, 1H), 4.30–4.70 (m, 2H), 6.98/7.03 (2s, 1H), 7.05/7.10 (2s, 1H),
7.60/7.80 (2dd, J = 8.5, 5.3 Hz, 1H), 7.96 (br, 1H), 8.36/8.50 (2d,
J = 8.5 Hz, 1H), 8.77/8.90 (2s, J = 5.3 Hz, 1H) (exchangeable NH and
OH not observed). 31P NMR (162 MHz, D2O): d 24.42. 19F NMR
2H, indole CH), 7.79 (br s, 1H, NH), 7.83 (m, 1H, quinoline CH), 8.16
(s, 1H, quinoline CH), 8.67 (d, 1H, quinoline CH, 3JHH = 8.6 Hz), 9.29
(d, 1H, quinoline CH, JHH = 4.4 Hz), 11.40 (s, 1H, indole NH). 13C
3
NMR (DMSO-d6, 100 MHz):
d
18.1 (NCH2CH2CH2SO3ꢀ), 39.7
(CHCH2Cl), 47.2 (HNCH2), 48.1 (CH2SO3ꢀ, CH2Cl), 49.1 (HNCH2),
55.5 (ONCH2), 55.9 (OCH3), 56.6 (NCH2ðCH2Þ2SO3ꢀ), 58.2
(CH2NðCH2Þ3SO3ꢀ), 60.9, 61.0 (OCH3), 62.0 (CH2NðCH2Þ3SO3ꢀ),
98.0, 106.2 (indole CH), 106.9 (quinoline CH), 111.4 (quinoline qua-
ternary C), 123.0 (indole quaternary C), 123.9 (quinoline CH), 125.3
(quinoline quaternary C), 125.8, 130.9 (indole quaternary C), 135.4
(quinoline CH), 139.0, 139.7 (indole quaternary C), 142.9, 145.7
(quinoline quaternary C), 148.3 (quinoline CH), 149.1 (indole qua-
ternary C), 160.8 (CO), 166.1 (quinoline quaternary C). Analysis
(CoC38H51ClN7O11S2ꢁ4H2O) Calcd: C, 45.08; H, 5.87; N, 9.68; Cl,
(376 MHz, D2O):
d
ꢀ78.89. HRMS (FAB, +ve): 832.23854/
3.50. Found: C, 45.02; H, 5.83; N, 9.80; Cl, 3.21. HRMS (FAB, +ve):
834.23901 [M]+, calcd for C36H4935/37ClCoN7O8P: 832.24008/
834.23713. Anal. Calcd for C37H49ClCoF3N7O11PSꢁ5H2O: C, 41.44;
H, 5.55; N, 9.14; S, 2.99. Found: C, 41.57; H, 5.27; N, 9.23; S, 3.03.
m/z 940.21836/942.21650 [M+H]+, calcd for CoC38H51
-
35/37
ClN7O11S2: 940.21868/942.21573.
4.2.5. 1-(Chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)
carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]-5-quinolinolato
(1,4,7,10-tetraazacyclododecane-1,7-dibutane-4,40-
diphosphonate)cobalt(III) [Co(H3L10)(4)] (10)
4.2.3. 1-(Chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)
carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]-5-quinolinolato
(1,4,7,10-tetraazacyclododecane-1-butane-4-sulfonate)
cobalt(III) chloride [Co(L8)(4)](OTf) (8)
A suspension of 4 (0.024 g, 0.052 mmol) in MeOH (10 mL) and
pyridine (0.022 g, 0.283 mmol) was added to a suspension of
[Co(H2L10)Cl2]7 (0.030 g) in MeOH (10 mL), and the mixture was
stirred under nitrogen at 50 °C for seven days to give a green solution
and green precipitate. The precipitate was filtered off and retained.
The filtrate was concentrated to about 2 mL under reduced pressure,
and filtered to remove a yellow precipitate. The green-yellow filtrate
was chromatographed on a Sephadex LH-20 gel filtration column,
eluting with MeOH. The first major green band was collected and
was reduced to dryness to give a green crystalline solid. This was
combined with the green reaction precipitate to give [Co(H2L10)(4)]
(10) (24.0 mg, 48%): 1H NMR (CD3OD, 400 MHz): d 1.02–1.45, 1.64
(m, 15H, side chain CH2), 2.38 (m, 2H, side chain CH2, macrocycle
CH2), 2.64, 2.74, 2.86, 3.09, 3.24, 3.45 (m, 15H, macrocycle CH2),
3.85 (m, 1H, CH2Cl), 3.90, 3.91 (s, 6H, OCH3), 3.98 (dd, 1H, CH2Cl,
A mixture of [Co(HL8)(OTf)2](OTf)7 (0.122 g, 0.15 mmol), 4
(0.070 g, 0.15 mmol) and pyridine (0.075 mL, 0.75 mmol) in MeOH
(15 mL) was stirred under nitrogen at 50 °C for 45 h to give a green
solution with some precipitate. The mixture was concentrated to a
volume about 5 mL and cooled in freezer to give more precipitate.
The precipitate was filtered, redissolved in warm MeOH and chro-
matographed on a Sephadex LH-20 gel filtration column using
MeOH as eluant. The first major green band was collected and re-
duced to dryness to give the product [Co(L8)(4)](OTf) (8) (78.0 mg,
53%) as green solid: 1H NMR (DMSO-d6, 400 MHz): d 0.97, 1.29,
1.46, 2.06 (m, 16H, CH2), 2.28, 2.38, 2.67–3.01, 3.24, 3.46 (m, 32H,
NCH2), 3.80, 3.82 (s, 12H, OCH3), 3.94 (m, 8H, CH2Cl, OCH3), 4.03
(m, 2H, CH2Cl), 4.21, 4.30 (m, 2H, CHCH2Cl), 4.39, 4.51 (d, 2H,
CONCH2, 2JHH = 10.8 Hz), 4.72, 4.94 (t, 2H, CONCH2, 2JHH = 10.8 Hz),
5.96, 6.64, 6.78 (br s, 4H, NH), 6.96 (s, 2H, indole CH), 7.08 (d, 2H, in-
3
2JHH = 11.4 Hz, JHH = 3.8 Hz), 4.07 (s, 3H, OCH3), 4.32 (m, 1H,
4
dole CH, JHH = 2.0 Hz), 7.55 (br s, 2H, NH), 7.81 (m, 2H, quinoline
CHCH2Cl), 4.71 (dd, 1H, CONCH2, 2JHH = 10.9 Hz, 4JHH = 2.2 Hz), 4.87
(dd, 1H, CONCH2, 2JHH = 10.8 Hz, 3JHH = 8.9 Hz), 6.99, 7.15 (s, 2H, in-
CH), 8.05 (s, 2H, quinoline CH), 8.67 (d, 2H, quinoline CH,