Helvetica Chimica Acta – Vol. 91 (2008)
2095
1
,1’-Bis(bis-(6,6’-oxymethylenyl-2,2’-bipyridine)binaphthyl (¼ 8,29,42,63-Tetraoxa-69,70,71,72-tetra-
2,6 31,35 36,40 9,18 12,17 19,28 20,25 43,52 46,51 53,62 54,59
azatridecacyclo[63.3.1.1 .1 .1 .0 .0 .0 .0 .0 .0 .0 .0 ]doheptaconta-1(69),2(72),
,5,9(18),10,12,14,16,19,21,23,25,27,31(71),32,34,36(70),37,39,43(52),44,46,48,50,53,55,57,59,61,65,67-do-
3
triacontaene; L2). Yield: 0.79 g (85%). M.p. 210 – 2158. IR: 3440w, 3072m, 1619s, 1571s, 1504s, 1436s,
1
1
(
401w, 1350w, 1328s, 1270s, 1244w, 1212s, 1148s, 1017s, 908w, 860w, 803s, 787s, 745s, 633m. H-NMR: 5.17
13
s, 4 CH ); 6.65 – 6.83 (m, 4 H); 7.23 – 7.65 (m, 18 H); 7.85 – 8.06 (m, 14 H). C-NMR: 71.93 (CH );
2
2
1
1
15.37; 119.66; 120.38 (C); 120.89; 123.99; 125.64; 126.68; 128.14; 129.66; 134.34 (C); 137.36; 153.98 (C);
þ
þ
55.15 (C); 156.20 (C); 157.30 (C). FAB-MS: 933 (70, [M þ H] ), 955 (70, [M þ Na] ). Anal. calc. for
C H N O · H O (951.09): C 80.82, H 4.87, N 5.89; found: C 80.45, H 4.86, N 5.90.
64
44
4
4
2
1
,1’-Bis(bis-(2,9-oxymethylenyl-1,10-phenanthroline)binaphthyl (¼ 3,24,37,58-Tetraoxa-69,72,73,76-
26,35 4,13 7,12 14,23 15,20 29,75 32,74 38,47 41,46 48,57 49,54 63,71 66,70
tetraazapentadecacyclo[58.8.4.4 .0 .0 .0 .0 .0 .0 .0 .0 .0 .0 .0 .0 ]hexahepta-
conta-1(69),4(13),5,7(12),8,10,14(23),15(20),16,18,21,26(76),27,29(75),30,32(74),33,35(73),38,40,42,
4
3
8
4,46,48,50,52,54,56,60(72),61,63(71),64,66(70),67-tetratriacontaene; L3). Yield: 0.75 g (76%). IR:
408m, 3072w, 1619s, 1596s, 1555w, 1491s, 1388w, 1347w, 1328s, 1280s, 1238w, 1113m, 1084m, 947w,
1
57w, 838w, 784s, 726s, 636m, 604w. H-NMR: 5.03 (s, 4 CH ); 7.14 (d, J ¼ 7.0, 4 H); 7.29 – 7.39 (m, 20 H);
2
13
7
.88 (d, J ¼ 7.0, 4 H); 7.96 – 7.99 (m, 8 H). C-NMR: 71.82; 111.12; 117.99; 124.22; 124.43; 126.92; 127.67;
1
28.61; 129.68; 131.61; 133.64; 136.05; 140.52; 146.02; 150.90; 152.99; 162.73. FAB-MS: 981 (100, [M þ
þ
H] ). Anal. calc. for C H N O (981.12): C 83.25, H 4.52, N 5.71; found: C 83.42, H 4.76, N 5.98.
68
44
4
4
Syntheses of Acyclic Ligands L4 and L5. To a soln. of 2 (0.29 g, 1 mmol) in hot anh. DMF (5 ml) was
added K CO (0.14 g, 1 mmol). The soln. was gently boiled, and 6-methyl-6’-bromomethyl-2,2’-
2
3
bipyridine (5, 0.53 g, 2 mmol) for L4 or 2-bromo-6-methylpyridine (0.35 g, 2 mmol) for L5 in 3 ml anh.
DMF was added during 30 min. Gentle reflux was maintained for 2 h, and 2 ml of the solvent were
distilled off from the mixture, which was then poured into H O (40 ml). Creamy solids were filtered off
2
and washed with dilute aq. NaOH soln. and H O, then dried.
2
1
,1’-Bis(6-methyl-6’-oxymethylenyl-2,2’-bipyridine)binaphthyl (¼6,6’-[1,1’-Binaphthalene-2,2’-diyl-
bis(oxymethanediyl)]bis(6’-methyl-2,2’-bipyridine); L4). Yield: 0.52 g (80%). M.p. 90 – 958. IR: 1619w,
1
571s, 1504m, 1440s, 1392w, 1347w, 1328m, 1270m, 1241m, 1212m, 1148s, 1084s, 806s, 784s, 748s, 633m.
1
H-NMR: 2.63 (s, 2 Me); 5.27 (s, 2 CH ); 6.74 (d, J ¼ 7.3, 2 H); 7.14 (d, J ¼ 7.3, 2 H); 7.34 – 7.39 (m, 8 H),
2
7
.48 (d, J ¼ 9.0, 2 H); 7.66 (t, J ¼ 7.6, 2 H); 7.88 (d, J ¼ 7.6, 2 H); 7.96 (d, J ¼ 9.0, 2 H); 8.08 (d, J ¼ 7.9,
13
2
1
1
H); 8.16 (d, J ¼ 7.9, 2 H). C-NMR: 24.67 (Me); 72.05 (CH ); 115.48; 115.61; 118.12; 118.53; 119.94;
2
20.92; 123.48; 124.01; 125.36; 125.70 (C); 126.68 (C); 128.17; 128.31 (C); 129.694; 134.42 (C); 137.50;
54.09 (C); 155.58 (C); 157.42 (C); 157.99 (C). FAB-MS: 651 (70, [M þ H] ). Anal. calc. for C H N O
þ
44
34
4
2
(
650.78): C 81.21, H 5.27, N 8.61; found: C 80.84, H 5.03, N 8.64.
1
,1’-Bis(2-methyl-6-oxypyridine)binaphthyl (¼2,2’-[1,1’-Binaphthalene-2,2’-diylbis(oxy)]bis(6-meth-
ylpyridine); L5). Yield: 0.23 g (50%). M.p. 215 – 2238. IR: 3328m, 3072w, 1616s, 1587s, 1555w, 1500s,
1
7
440s, 1398w, 1334s, 1273s, 1235m, 1209w, 1171m, 1145w, 1129w, 1004m, 976s, 966s, 931m, 809s, 787m,
1
52s, 675m, 627m. H-NMR: 2.49 (s, 2 Me); 7.10 – 7.13 (m, 4 H); 7.26 – 7.36 (m, 8 H); 7.84 – 7.95 (m, 6 H).
1
3
C-NMR: 24.32 (Me); 111.12 (C); 117.98; 122.28; 124.22; 124.42; 125.21; 127.66 (C); 128.60; 129.67;
þ
1
31.59; 133.64 (C); 138.74; 141.53 (C); 152.97 (C); 160.22 (C). FAB-MS: 469 (100, [M þ H] ). Anal. calc.
for C H N O (468.55): C 82.03, H 5.16, N 5.98; found: C 81.91, H 4.97, N 5.78.
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24
2
2
Activity. Cell Cultures. A549 (Human Lung Carcinoma Epithelial like) cell lines were obtained from
the Institute for Fermentation, Osaka (IFO, Japan). A549 Cells were maintained as a monolayer in
Nutrient Mixture F-12 HAM Medium (Sigma) containing 10% (v/v) heat-inactivated fetal bovine serum
(
Sigma), penicillin-streptomycin (Sigma), and NaHCO
3
. The A549 cells were incubated at 378 in a
3
humidified atmosphere of 5% (v/v) CO2 in air. Cells were plated at 5 ꢁ 10 cells/ml into 96-well
microtiter tissue culture plates (Techno Plastic Products AG) and then incubated for 24 h before addition
of the test samples. Stock solns. of these samples were initially prepared in DMSO (Sigma), stored at 48
and further diluted in fresh complete medium.
In vitro Cytotoxicity Assay. The growth inhibitory effects of the compounds were measured using the
MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay [20]. Cells were seeded in
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9
6-multiwell plates at a density of 5 ꢁ 10 cells/well. After a 24-h preincubation period, the medium was
changed and the cells were treated with different concentrations of the freshly prepared test compounds
in complete medium. Negative control groups were untreated cells and positive control groups were the