Preparation of tryptanthrin Schiff base based N, N- donor ligands (L1-L7) and Pt(II)metal complexes
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Synthesis of the tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione, 1-H) was done by adding solution of the isatoic anhydride to the boil solution of the toluene followed by refluxing the reaction mixture for 60–70 min [9]. The precipitated product was washed with methanol and used for further reaction. Schiff base of the tryptanthrin was obtained through stirring the equimolar amount of the tryptanthrin and substituted phenylhydrazine hydrochloride in methanol at room temperature for 4–6 hours. The crude was filtered, washed with methanol, and recrystallized from a mixture of methanol and chloroform. Metal complexes of the tryptathrin based ligand were prepared by adding methanolic solution of ligand into K2PtCl4 solution in methanol and reflux for 2–3 h and then stirred at RT for 20 h.[30]
Characterization Data
(E)-6-(2-Phenylhydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L1)
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Empirical formula: C21H14N4O; % Yield:79.82; Color: Orange fluffy solid; M.P.: >300°C; M.W.:338.37 gm/mol; calc.(%): C, 74.54; H, 4.17; N, 16.56; Found. (%): C, 74.43; H, 4.28; N, 16.62; m/z(%):338 (100) [M]+, 339 [M + 1]; 1H NMR (400 MHz, CDCl3) δ/ppm: 13.37 (1H, s, H2’), 8.52 (1H, d, J = 8Hz, H2), 8.40 (1H, d, J = 7.6Hz, H5), 7.71–7.81 (3H, m H5’6’7’), 7.51 (1H, t, J = 7.6Hz H3), 7.28–7.44 (6H, m, H7, 8, 9, 10, 4’, 8’), 7.11(1H, t, J = 8Hz, H4); IR(4000–450 cm–1): 3051 ѵ(= C-H) Stretchig 1580 ѵ(C = N)Stretching, 1609 ѵ(C = O)Stretching, 1478 ѵ(C = C)ar. Stretching, 1171 ѵ(C-N)Stretching.
(E)-6-(2-(4-Chlorophenyl)hydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L2)
Empirical formula: C21H13ClN4O; % Yield: 76.32; Color: yellowish fluffy solid; M.P.: >300°C; M.W.: 372.82 gm/mol.; calc.(%): C, 67.66; H, 3.51; N, 15.03; Found. (%):C, 67.78; H, 3.60; N, 14.94; m/z(%):372 (100) [M]+, 374 [M + 2]; 1H NMR (400 MHz, CDCl3) δ/ppm: 13.50 (1H, s, H2’), 8.53 (1H, d, J = 8Hz, H2), 8.47 (1H, d, J = 7.6Hz, H5), 7.81–7.86 (3H, m H5’,7’,8), 7.59 (1H, t, J = 7.0Hz H3), 7.40–7.52 (5H, m, H7, 9, 10, 4’, 8’), 7.16(1H, t, J = 8Hz, H4); IR Spectra (KBr, 4000–450 cm− 1 ) 3050 ѵ(= C-H)ar. Stretching, 1605 ѵ(C = O)Stretching, 1586 ѵ(C = N)ar. Stretching, 1483 ѵ(C = C)ar. Stretching, 1396 ѵ(C-N)ar. Stretching, 748 ѵ(= C-H)bending, 663 ѵ(C-H)bending 556 v(C-Cl).
(E)-6-(2-(4-Bromophenyl)hydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L3)
Empirical formula: C21H13BrN4O; %Yield:79.15, Color: Dark yellowish fluffy solid; M.P.: >300°C; M.W.: 417.27; gm/mol calc. (%):C, 60.45; H, 3.14; N, 13.43; Found. (%):C, 60.57; H, 3.26; N, 13.54; m/z(%):417 (100) [M]+, 419 [M + 2] (95); 1H NMR (400 MHz, CDCl3) δ/ppm: 13.49 (1H, s, H2’), 8.53 (1H, d, J = 8Hz, H2), 8.47 (1H, d, J = 7.6Hz, H5), 7.60–7.85 (3H, m H5’,7’,8), 7.59 (1H, t, J = 7.0Hz H3), 7.40–7.58 (5H, m, H7, 9, 10, 4’, 8’), 7.16(1H, t, J = 8Hz, H4); IR Spectra (KBr, 4000–450 cm− 1 ) 3048 ѵ(= C-H)ar. Stretching, 1605 ѵ(C = O)Stretching, 1585 ѵ(C = N)ar. Stretching, 1480 ѵ(C = C)ar. Stretching, 1395 ѵ(C-N)ar. Stretching, 818 ѵ(C-Br)stretching, 754 ѵ(= C-H)bending, 663 ѵ(C-H)bending
(E)-6-(2-(p-Tolyl)hydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L4)
Empirical formula: C22H16N4O; %Yield: 89.11; Color: yellowish fluffy solid;M.P.: >300°C; M.W.: 352.4 gm/mol; calc. (%):C, 74.98; H, 4.58; N, 15.90; Found. (%):C, 74.89; H, 4.65; N, 15.84; m/z(%):352 (100) [M]+, 1H NMR (400 MHz, CDCl3) δ/ppm: 13.34 (1H, s, H2’), 8.35 (2H, m, H2, 5), 7.79–7.55 (3H, m, H3,4,8), 7.51(1H, t, J = 6.4Hz H9) 7.32-7. 46 (4H, m, H4’,5’,7’, 8’),7.00-7.24 (2H, m, H7, 10), 2.44(3H, s, -CH3); IR Spectra (KBr, 4000–400 cm− 1): IR Spectra (KBr, 4000–450 cm− 1 ) 3042 ѵ(= C-H)ar. Stretching, 1607 ѵ(C = O)Stretching, 1588 ѵ(C = N)ar. Stretching, 1481 ѵ(C = C)ar. Stretching, 1389 ѵ(C-N)ar. Stretching, 755 ѵ(= C-H)bending, 661 ѵ(C-H)bending .
(E)-8-Chloro-6-(2-phenylhydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L5)
Empirical formula: C21H13ClN4O; %Yield: 89.11; Color: yellowish fluffy solid; M.P.: >300°C; M.W.: 372.82gm/mol; calc. (%):C, 67.66; H, 3.51; N, 15.03; Found. (%):C, 67.73; H, 3.59; N, 15.11; m/z(%):372 (100) [M]+, 374 [M + 2] ; 1H NMR (400 MHz, CDCl3) δ/ppm: 13.50 (1H, s, H2’), 8.53 (1H, d, J = 8Hz, H2), 8.47 (1H, d, J = 7.6Hz, H5), 7.81–7.86 (3H, m H5’,7’,8), 7.59 (1H, t, J = 7.0Hz H3), 7.40–7.52 (5H, m, H7, 9, 10, 4’, 8’), 7.16(1H, t, J = 8Hz, H4); IR Spectra (KBr, 4000–400 cm− 1): IR Spectra (KBr, 4000–450 cm− 1 ) 3053 ѵ(= C-H)ar. Stretching, 1615 ѵ(C = O)Stretching, 1489 ѵ(C = C)ar. Stretching, 1578 ѵ(C = N)ar. Stretching, 1396 ѵ(C-N)ar. Stretching, 753 ѵ(= C-H)bending, 656 ѵ(C-H)bending.
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(E)-8-Bromo-6-(2-phenylhydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L 6 ) Empirical formula: C21H13BrN4O %Yield: 89.11; Color: yellowish fluffy solid; M.P.: >300°C; M.W.: 417.27gm/mol; calc. (%):C, 60.45; H, 3.14; N, 13.43; Found. (%):C, 60.53; H, 3.23; N, 13.51; m/z(%):417 (100) [M]+, 419 [M + 2] ; 1H NMR (400 MHz, CDCl3) δ/ppm: 13.48 (1H, s, H2’), 8.40–8.50 (2H, m, H8,7), 8.01 (1H, s, H10), 7.81–7.87 (2H, m H2,3), 7.52–7.59 (2H, m, H4,5), 7.43–7.58 (4H, m, H4’,5’,7’, 8’), 7.16(1H, t, J = 7.6Hz, H6’); IR Spectra (KBr, 4000–450 cm–1 ) 3048 ѵ(= C-H)ar. Stretching, 1612 ѵ(C = O)Stretching, 1492 ѵ(C = C)ar. Stretching, 1586 ѵ(C = N)ar. Stretching,1395 ѵ(C-N)ar. Stretching, 753 ѵ(= C-H)bending, 817 ѵ(C-Br)stretching, 663 ѵ(C-H)bending
(E)-8-Methyl-6-(2-phenylhydrazineylidene)indolo[2,1-b]quinazolin-12(6H)-one (L7)
Empirical formula: C22H16N4O %Yield: 89.11; Color: yellowish fluffy solid; M.P.: >300°C; M.W.: 352.4 gm/mol; calc. (%):C, 74.98; H, 4.58; N, 15.90; Found. (%):C, 74.87; H, 4.64; N, 15.82; m/z(%):352 (100) [M]+; 1H NMR (400 MHz, CDCl3) δ/ppm: 13.46 (1H, s, H2’), 8.38–8.53 (2H, m, H8,7), 7.7 (1H, s, H10), 7.75–7.86 (2H, m H2,3), 7.31–7.60 (4H, m, H4’, 5’, 7’, 8’), 7.23–7.29 (2H, m, H4,5), 7.16(1H, t, J = 7.2Hz, H6’) 2.49 (3H, s, -CH3); IR Spectra (KBr, 4000–400 cm− 1): ) 3046 ѵ(= C-H)ar. Stretching, 1613 ѵ(C = O)Stretching, 1496 ѵ(C = C)ar. Stretching, 1582 ѵ(C = N)ar. Stretching, 1393 ѵ(C-N)ar. Stretching, 754 ѵ(= C-H)bending, 663 ѵ(C-H)bending.
[Pt(L1)Cl2] (I)
Empirical formula: C21H14Cl2N4OPt %Yield: 59.78; Color: black solid; M.P.: > 300°C; M.W.: 604.35 gm/mol; Conductance: 18.72 ohm− 1cm2mol− 1; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.44 (1H, s, H2’), 8.49 (1H, d, J = 6.4Hz, H2), 8.36 (1H, d, J = 7.2Hz, H7), 8.14 (1H, d, J = 6.8Hz, H5), 7.86–8.01 (2H, m H10,3), 7.25–7.77 (7H, m, H8, 9, 4’, 5’,6’, 7’, 8’), 7.14(1H, t, J = 6.4Hz, H4); IR Spectra (KBr, 4000–450 cm− 1 ) 3087 ѵ(= C-H)ar. Stretching, 1673 ѵ(C = O)Stretching,1611 ѵ(C = N)ar. Stretching,1608 ѵ(C = C)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending,555 ѵ(Pt-N).
[Pt(L2)Cl2] (II)
Empirical formula: C21H13Cl3N4OPt; %Yield: 57.43 Color: black solid; M.P.: > 300°C M.W.: 638.80 gm/mol; Conductance: 14.57 ohm− 1cm2mol− 1; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.43 (1H, s, H2’), 8.48 (1H, d, J = 6.4Hz, H2), 8.35 (1H, d, J = 7.2Hz, H7), 8.16 (1H, d, J = 6.8Hz, H5), 7.91–8.04 (2H, m H10,3), 6.44–7.78 (7H, m, H4, 8, 9, 4’, 5’, 7’, 8’); IR Spectra (KBr, 4000–450 cm− 1): 3092 ѵ(= C-H)ar. Stretching, 1665 ѵ(C = O)Stretching, 1619 ѵ(C = C)ar. Stretching, 1613 ѵ(C = N)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 817 ѵ(C-Br)stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending, 524 ѵ(Pt-N) .
[Pt(L3)Cl2] (III)
Empirical formula: C21H13BrCl2N4OPt %Yield: 56.86, Color: dark brown crystalline solid; M.P.: > 300°C M.W.: 683.25 gm/mol; Conductance: 18.35 ohm− 1cm2mol− 1; 1H NMR (400 MHz, DMSO-d6) δ/ppm13.41 (1H, s, H2’), 8.49 (1H, d, J = 6.4Hz, H2), 8.36 (1H, d, J = 7.6Hz, H7), 8.17 (1H, d, J = 7.8Hz, H5), 7.82–8.01 (3H, m H3, 4, 8), 7.52–7.72 (5H, m, H10, 4’, 5’, 7’, 8’), 7.47(1H, t, J = 6.4Hz, H9); IR Spectra (KBr, 4000–450 cm− 1): 3082 ѵ(= C-H)ar. Stretching, 1621 ѵ(C = C)ar. Stretching, 1668 ѵ(C = O)Stretching,1618 ѵ(C = N)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 817 ѵ(C-Br)stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending, 570 ѵ(Pt-N).
[Pt(L4)Cl2] (IV)
Empirical formula: C22H16Cl2N4OPt %Yield: 58.48, Color: black crystalline solid; M.P.: > 300°C M.W.: 618.38 gm/mol; Conductance: 22.61 ohm− 1cm2mol− 1 ; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.41 (1H, s, H2’), 7.23–8.55 (12H, m, H2, 3, 4, 5,7, 8, 9, 10, 4’, 5’, 7’, 8’), 2.48 (3H, s,-CH3); IR Spectra (KBr, 4000–450 cm− 1): 3085 ѵ(= C-H)ar. Stretching, 1671 ѵ(C = O)Stretching, 1613 ѵ(C = C)ar. Stretching, 1615 ѵ(C = N)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending,547 ѵ(Pt-N).
[Pt(L5)Cl2] (V)
Empirical formula: C21H13Cl3N4OPt %Yield: 59.78, Color: brown crystalline solid; M.P.: > 300°C M.W.: 638.80 gm/mol ; Conductance: 16.62 ohm− 1cm2mol− 1; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.41 (1H, s, H2’), 8.49 (1H, d, J = 7.6Hz, H2), 8.35 (1H, d, J = 6.4Hz, H7), 8.16 (1H, d, J = 5.6Hz, H5), 7.82–8.01 (3H, m H4’, 6’, 8’), 7.40–7.78 (6H, m, H5’, 7’, 3, 4, 8, 10); IR Spectra (KBr, 4000–450 cm− 1): 3087 ѵ(= C-H)ar. Stretching, 1678 ѵ(C = O)Stretching,1617ѵ(C = C)ar. Stretching, 1614ѵ(C = N)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending, 565 ѵ(Pt-N).
[Pt(L6)Cl2] (VI)
Empirical formula: C21H13BrCl2N4OPt %Yield: 57.24; Color: brown solid; M.P.: > 300°C M.W.: 683.25 gm/mol; Conductance: 15.62 ohm− 1cm2mol− 1 ; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.44 (1H, s, H2’), 8.35–8.48 (2H, m, H8,7), 8.56 (1H, s, H10), 6.88–8.38 (9H, m H2,3,4,5, 4’,5’,6’,7’, 8’); IR Spectra (KBr, 4000–450 cm− 1): 3084 ѵ(= C-H)ar. Stretching, 1687 ѵ(C = O)Stretching, 1620 ѵ(C = N)ar. Stretching, 1614 ѵ(C = C)ar. Stretching, 1392 ѵ(C-N)ar. Stretching, 817 ѵ(C-Br)stretching, 753 ѵ(= C-H)bending, 663 ѵ(C-H)bending, 573 ѵ(Pt-N).
[Pt(L7)Cl2] (VII)
Empirical formula: C22H16Cl2N4OPt %Yield: 54.61% Color: brown crystalline solid; M.P.: > 300°C M.W.: 618.38 gm/mol; Conductance: 19.56 ohm− 1cm2mol− 1 ; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 13.42 (1H, s, H2’), 8.34–8.52 (2H, m, H8,7), 7.32–7.83 (6H, m H2,3,10 ,6’), 7.32–7.83 (4H, m, H4, 5, 4’, 5’, 7’, 8’), 2.49 (3H, s, -CH3); IR Spectra (KBr, 4000–450 cm− 1): 3079 ѵ(= C-H)ar. Stretching, 1683 ѵ(C = O)Stretching,1620 ѵ(C = C)ar. Stretching, 1612 ѵ(C = N)ar. Stretching, 1380 ѵ(C-N)ar. Stretching, 748 ѵ(= C-H)bending, 667 ѵ(C-H)bending, 570 ѵ(Pt-N).
Computational study
DFT
DFT study was performed on Gaussian 9 software package using B3LYP basis set as an L
nL2DZ function.
Docking
A molecular docking study was performed using HEX 8.0 program with windows 7 operating system. The optimized structure of the compounds from the DFT calculation was used as an input file in PDB format. For Autodock Vina PDBQT file was converted from the PDB file using MGL tools. A docking study was performed with grid dimension 98×58×56 Point (X×Y×Z).
Biological Study
Antibacterial and cytotoxicity study
Antibacterial study was performed using broth dilution method as reported in the literature[31]. Cytotoxicity study on the Artemia cyst is portrayed as the process reported by Meyer et al.,[32]
DNA binding study
According to previously published literature, all the binding studies, including DNA and BSA binding, using UV-visible and spectrofluorometer [27, 29]. DNA used for the binding study is CT-DNA and the concentration of the DNA used was 200µM which is calculated using the extinction coefficient(6600M-1cm-1) in Beer-Lambert Law.