P. Chellan et al.
Journal of Inorganic Biochemistry 219 (2021) 111408
H), 8.75 (d, J(H-H): 4.5 Hz, 1H, bipy-H), 8.51 (d, J(H-H): 4.5 Hz, 1H,
bipy-H), 8.15 (s, 1H, bipy-H), 7.86 (d, J(H-H): 5.0 Hz, 1H, bipy-H), 7.09
acetone-d
6
) δ (ppm) = 152.29, 151.38, 150.77, 130.41, 130.11, 129.62,
129.46, 129.21, 125.99, 125.35, 123.92, 123.37, 119.01, 89.84, 44.61,
36.54, 35.80, 31.48, 29.20, 28.90, 24.94, 19.73. HR-ESI-MS for
(
d, J(H-H): 5.0 Hz, 1H, bipy-H), 5.97 (d, J(H-H): 10.0 Hz, 1H, ART-H),
.45 (s, 1H, ART-H), 2.71–2.77 (m, 1H, ART-H), 2.38 (s, 3H, bipy-
CH
), 2.30–2.33 (m, 1H, ART-H), 1.63–1.85 (m, 7H, ART-H), 1.37 (s,
H, ART-CH ), 0.90 (t, J(H-H): 8.0 Hz, 6H,
C{ H} NMR (101 MHz, acetone-d
): δ (ppm) = 170.9
ꢀ +
5
C
42
H49ClF
6
IrN
2
O
6
P, calculated for ([M – PF
6
] ): 905.2897, found: m/z
3
905.2911 (100%). HPLC purity: >99%; tr’ = 14.47 min.
3
3
), 1.20–1.26 (m, 3H, ART-CH
3
1
3
1
2.3.2.3. [ 5
-(Tetramethylbiphenylcyclopentadienyl)IrCl(N,N -methylbipyr-
′
ART-CH
3
).
6
η
′
′
(
C=Oester), 164.6 (ART) 158.4, 155.7 (bipy), 151.2, 150.2 (bipy), 138.9
ART), 1126.20, 123.6, 122.4, 120.7 (bipy), 104.8 (ART), 96.4, 94.4,
2.3, 91.6, 88.2, 80.9, 66.1, 60.6, 52.6, 46.2, 37.7, 37.2, 35.0 32.9, 26.0
ART), 26.0, 21.2, 20.6, 12.52 (ART-CH3, bipy-CH ). HR-ESI-MS for
idylarte-misinyl ester)]PF6 (3). Methyl-4 -carboxy-2,2 -bipyridine dihy-
droartemisinin ester (L1) (0.050 g, 0.104 mmol) was reacted
with dichloro(tetramethylbiphenylcyclopentadienyl)iridium(III) dimer
(0.056 g, 0.052 mmol) and ammonium hexafluorophosphate (0.017 g,
0.104 mmol). The product (3) was isolated as a bright orange micro-
(
9
(
3
+
C
27
H
32
2
N O
6
,
calculated for ([M + Na] ): 503.2153, found: m/z
crystalline solid (0.109 g, 93%). 1H NMR (500 MHz, acetone-d ) δ
5
03.2150 (100%). HPLC purity: 95%; tr’ = 12.81 min.
6
(
ppm) = 9.19–9.10 (m, 1H, bipy-H), 9.01–8.92 (m, 1H, bipy-H),
2
.3.2. General synthetic method for Rh(III) and Ir(III) bipyridyl-
8.90–8.80 (m, 2H, bipy-H), 8.83–8.71 (m, 1H, bipy-H), 8.35 (m, 1H,
x
x
artemisinyl complexes (1–6)
bipy-H), 7.92–7.72 (m, 7H, Cp -Ar-H), 7.58–7.41 (m, 2H, Cp -Ar-H),
6.04 (d, J = 9.8 Hz, 1H, ART-H), 5.62 (s, 1H, ART-H), 2.75–2.61 (m, 4H,
′
′
The ligand, 4-methyl-4 -carboxy-2,2 -bipyridine dihydroartemisinin
ester (L1, 2 mol equiv) was dissolved in methanol (15 mL) and a solution
of the appropriate rhodium or iridium dimer (1 mol equiv.) in DCM
ART-CH ), 2.39–2.27 (m, 1H, ART-H), 2.16–2.02 (m, 2H, ART-H),
3
x
x
2.00–1.23 (m, 22H, ART-H, Cp -CH ), 1.15–0.96 (m, 6H, ART-H, Cp -
3
1
3
1
(
10 mL) was added and the reaction solution was stirred for 16 h at room
CH ). C{ H} NMR (126 MHz, acetone-d ) δ (ppm) = 196.55, 194.47,
3
6
temperature. Ammonium hexafluorophosphate (2 mol equiv.) was then
added and reaction stirred for a further 1 h. The solvent was then
evaporated, and the orange yellow residue was re-dissolved in acetone
152.09, 151.28, 131.05, 130.18, 129.64, 129.19, 127.77, 126.88,
125.84, 125.39, 123.43, 89.99,
49.97, 35.01, 31.29, 28.90, 16.50. HR-ESI-MS for C48H53ClF Ir-
6
ꢀ +
(
10 mL) filtered through celite to remove insoluble inorganic salts. The
N O P, calculated for ([M – PF ] ): 981.3211, found: m/z 981.3227
2
6
6
volume of the filtrate was reduced to ca. 3 mL. The product was then
precipitated from solution by addition of diethyl ether and isolated by
vacuum filtration, washed with diethyl ether and dried.
(100%). HPLC purity: >99%; t = 19.92 (aqua), 21.70 (chloride) min.
r’
.3.2.4. [( 5
idylartemisinyl ester)]PF
η
-Pentamethylcyclopentadienyl)RhCl(N,N -methylbipyr-
′
2
′
′
6
(4). Methyl-4 -carboxy-2,2 -bipyridine dihy-
5
′
2
.3.2.1. [(
η
-Pentamethylcyclopentadienyl)IrCl(N,N -methylbipyr-
droartemisinin ester (L1) (0.050 g, 0.104 mmol) was reacted with
dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer (0.032 g,
0.052 mmol) and ammonium hexafluorophosphate (0.017 g,
′
′
idylartemisinyl ester)]PF
6
(1). Methyl-4 -carboxy-2,2 -bipyridine dihy-
droartemisinin ester (L1) (0.050 g, 0.104 mmol) was reacted with
dichloro(pentamethylcyclopentadienyl)iridium(III) dimer (0.041 g,
0.104 mmol). The product (4) was isolated as an orange microcrystalline
1
0
0
.052 mmol) and ammonium hexafluorophosphate (0.017 g,
solid (0.083 g, 89%).
H
NMR (500 MHz, acetone-d6)
δ
.104 mmol). The product (1) was isolated as a bright yellow micro-
(ppm) = 9.09–8.90 (m, 1H, bipy-H), 8.82–8.74 (m, 2H, bipy-H),
8.46–8.43 (m, 1H, bipy-H), 8.31–8.30 (m, 1H, bipy-H), 7.69–7.68 (m,
1H, bipy-H), 6.02 (d, J = 9.03 Hz, 1H, ART-H), 5.66 (s, 1H, ART-H),
1
crystalline solid (0.088 g, 86%). H NMR (400 MHz, acetone-d
6
): δ
(
ppm) = 9.33 (d, J(H-H): 6.0 Hz, 1H, bipy-H), 9.10 (d, J(H-H): 17.1 Hz,
1
8
H, bipy-H), 8.99 (d, J(H-H): 6.0 Hz, 1H, bipy-H), 8.86 (s, 1H, bipy-H),
.38 (t, J(H-H): 5.5 Hz, 1H, bipy-H), 7.80 (d, J(H-H): 5.5 Hz, 1H, bipy-
3.42–1.70 (d, J = 2.1 Hz, 25H, ART-H, Cp*-CH ), 1.67–1.45 (m, 3H,
3
1
3
1
ART-H), 1.40–1.26 (m, 4H, ART-H), 1.17–0.88 (m, 7H, ART-H). C{ H}
H), 6.05 (m, 1H, ART-H), 5.69 (s, 1H, ART-H), 2.75–2.65 (m, 3H,
ART-CH ), 2.05 (s, 3H, bipy-CH
), 1.60–1.95 (m, 22H, ART-H, Cp*-
CH ), 0.99 (m, 6H,
), 1.45–1.55 (m, 2H, ART-H), 1.11 (s, 3H, ART-CH
ART-CH
): δ (ppm) = 182.2,
79.3, 154.2, 152.2, 145.2, 141.2, 131.0, 130.9, 128.8, 123.7, 118.2,
NMR (126 MHz, acetone-d ) δ (ppm) = 152.82, 151.74, 136.06, 129.72,
6
3
3
129.45, 128.90, 125.55, 125.11, 123.15, 120.32, 91.59, 90.45, 86.46,
3
3
51.74, 34.98, 31.27, 29.21, 28.56, 8.55. HR-ESI-MS for
1
3
1
ꢀ +
3
). C{ H} NMR (101 MHz, acetone-d
6
C37H47ClF N O PRh, calculated for ([M – PF ] ): 753.2172, found: m/z
6
2
6
6
1
1
2
N
753.2186 (100%). HPLC purity: >99%; t = 10.46 (aqua), 13.31
r’
17.22, 116.7, 104.9, 95.4, 93.8, 92.4, 90.8, 77.6, 52.6, 46.1, 37.7, 37.0,
(chloride) min.
6.0, 25.4, 22.4, 21.2, 20.5, 14.9, 8.6. HR-ESI-MS for C37
H
47ClF
ꢀ +
6
] ): 843.2740, found: m/z 843.2757
6
Ir-
2
O
6
P, calculated for ([M – PF
′
2
.3.2.5. [( 5
idylartemisinyl ester)]PF
droartemisinin ester (L1) (0.050 g, 0.104 mmol) was reacted with
dichloro(tetramethylphenylcyclopentadienyl)rhodium(III) dimer
η
-Tetramethylphenylcyclopentadienyl)RhCl(N,N -methylbipyr-
(
100%). HPLC purity: >99%; tr’ = 9.16 min.
′
′
6
(5). Methyl-4 -carboxy-2,2 -bipyridine dihy-
5
′
2
.3.2.2. [(
η
-Tetramethylphenylcyclopentadienyl)IrCl(N,N -methylbipyr-
′
′
idylartemisinyl ester)]PF
droartemisinin ester (L1) (0.050 g, 0.104 mmol) was reacted with
dichloro(tetramethylphenylcyclopentadienyl)iridium(III) dimer
0.048 g, 0.052 mmol) and ammonium hexafluorophosphate (0.017 g,
6
(2). Methyl-4 -carboxy-2,2 -bipyridine dihy-
(0.039 g, 0.052 mmol) and ammonium hexafluorophosphate (0.017 g,
0.104 mmol). The product (5) was isolated as an orange microcrystalline
solid (0.088 g, 88%). 1H NMR (500 MHz, acetone-d ) δ 9.09–8.98 (m,
6
(
2H, bipy-H), 8.82 (m, 1H, bipy-H), 8.72–8.63 (m, 1H, bipy-H), 8.35 (m,
x
0
.104 mmol). The product (2) was isolated as a bright yellow micro-
1H, bipy-H), 7.83–7.55 (m, 6H, Cp -Ar-H, bipy-H), 6.04 (dd, J = 9.8,
1
crystalline solid (0.104 g, 95%). H NMR (500 MHz, acetone-d
6
) δ
3.9 Hz, 1H), 5.68 (d, J = 13.3 Hz, 1H), 2.74–2.61 (m, 4H), 2.39–2.27 (m,
(
ppm) = 9.16 (dd, J(H-H) = 4.3, 1.9 Hz, 1H, bipy-H), 9.11 (t, J = 5.6 Hz,
1H), 2.12–2.06 (m, 4H), 1.99–1.90 (m, 8H), 1.91–1.74 (m, 8H),
x
13
1
1
8
H, bipy-H) 9.00–8.89 (m, 1H, bipy-H), 8.84–8.79 (m, 1H, bipy-H),
.78–8.67 (m, 1H, bipy-H), 8.34 (m, 1H, bipy-H), 7.77–7.72 (m, 1H,
1.78–0.94 (m, 11H, ART-H, Cp -CH ).
C{ H} NMR (126 MHz,
3
acetone-d ) δ (ppm) = 152.42, 151.22, 130.90, 130.58, 129.77, 129.69,
6
x
x
x
Cp -Ar-H), 7.71–7.62 (m, 2H, Cp -Ar-H), 7.62–7.50 (m, 2H, Cp -Ar-H),
6
129.63, 129.44, 128.48, 125.99, 125.18, 123.49, 91.34, 44.89, 43.92,
.12–6.01 (m, 1H, ART-H), 5.68 (d, J = 9.6 Hz, 1H, ART-H), 2.75–2.62
36.47, 35.63, 31.44, 24.81, 9.95. HR-ESI-MS for C42H49ClF N O PRh,
6
2 6
ꢀ
+
(
m, 2H, ART-H), 2.34 (m, 1H, ART-H), 2.05 (s, 3H, ART-bipy-CH
3
),
calculated for ([M – PF ] ): 815.2329, found: m/z 815.2343 (100%).
6
x
2
.00–1.88 (m, 8H, ART-H), 1.90–1.40 (m, 16H, ART-H, Cp -CH
3
), 1.30
HPLC purity: 96%; t = 12.80 (aqua), 16.99 (chloride) min.
r’
x
x
13
1
(
3 3
s, 3H, Cp -CH ), 0.98 (s, 3H, Cp -CH ). C{ H} NMR (126 MHz,
4