Metal-based sulfonamides: Their preparation, characterization and in-vitro antibacterial, antifungal & cytotoxic properties. X-ray structure of 4-[(2-hydroxybenzylidene) amino] benzenesulfonamide

Figures & data

Figure 1 ORTEP diagram of a single molecule found in the asymmetric unit.

Scheme 1 Preparation of Ligands.

Table I.  Physical, Spectral and Analytical Data of the Metal (II) Complexes.

	M.P	Yield	B.M	IR	λmax	Calc. (Found) %
No	(^oC)	(%)	(μeff)	(cm^− 1)	(cm^− 1)	C	H	N
1. [Co(L3)(H2O)2] [645.57] C26H26N4O8S2 Co	211–213	83	4.80	3455 (NH2), 1575 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 440 (M–N) (M–O)	7290, 17420, 20470, 29310	48.37(48.62)	4.06 (4.33)	8.68 (8.42)
2. [Cu(L3)(H2O)2] [650.19] C26H26CuN4O8S2	206–208	81	1.72	3455 (NH2), 1565 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N) 845 (C–S), 425 (M–N) 510, (M–O)	14825, 19165 30355	48.03 (48.47)	4.03 (3.87)	8.62 (8.84)
3.[Ni(L3)(H2O)2] [645.33] C26H26NiN4O8S2	216–218	82	3.30	3455 (NH2), 1570 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 430 (M–N), 545 (M–O)	10435, 19165, 30355	48.03 (48.47)	4.03 (3.87)	8.62 (8.84)
4. [Zn(L3)(H2O)2] [652.03] C26H26ZnN4O8S2	212–214	80	Dia	3455 (NH2), 1568 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 437 (M–N), 528 (M–O)	28585	47.89 (47.69)	4.02 (4.46)	8.59 (8.73)
5. [Co(L4)(H2O)2] [673.63] C28H30CoN4O8S2	204–206	82	4.88	3455 (NH2), 1565 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 425 (M–N), 525 (M–O)	7470, 17510, 20670, 29385	49.92 (50.21	4.49 (4.18)	8.32 (8.65)
6. [Cu(L4)(H2O)2] [678.24] C28H30CuN4O8S2	206–208	84	1.67	3455 (NH2), 1575 (C = N), 1385 (C–O), 1315, 1140, (SO2), 960 (S–N), 845 (C–S), 428 (M–N), 520 (M–O)	15155, 19315, 30380	49.59 (49.33)	4.46 (4.69)	8.26 (8.43)
7. [Ni(L4)(H2O)2] [673.38] C28H30NiN4O8S2	209–211	81	3.25	3455 (NH2), 1570 (C = N) 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 432 (M–N), 533 (M–O)	10485, 15865, 26675, 30225	49.94 (50.37)	4.49 (4.16)	8.32 (8.16)
8. [Zn(L4)(H2O)2] [680.08] C28H30ZnN4O8S2	214–216	82	Dia	3455 (NH2), 1568 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 425 (M–N), 545 (M–O)	29140	49.45 (49.81)	4.45 (4.77)	8.24 (8.08)
9. [Co(L5)(H2O)2] [701.68] C30H34CoN4O8S2	212–214	83	4.76	3455 (NH2), 1565 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 435 (M–N), 510 (M–O)	7285, 17360, 20455, 29290	51.35 (51.16)	4.88 (4.58)	7.98 (8.24
10. [Cu(L5)(H2O)2] [706.29] C30H34CuN4O8S2	210–212	81	1.81	3455 (NH2), 1567(C = N) 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 430 (M–N), 520 (M–O)	14725, 19140, 30335	51.02 (51.42)	4.85 (4.67)	7.93 (7.68)
11. [Ni(L5)(H2O)2] [701.44] C30H34NiN4O8S2	218–220	82	3.27	3455 (NH2), 1570 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 440 (M–N), 535 (M–O)	10355, 15610, 26325, 29850	51.37 (51.67)	4.89 (4.52)	7.99 (8.28
12. [Zn(L5)(H2O)2] [708.14] C30H34ZnN4O8S2	207–209	83	Dia	3455 (NH2), 1568 (C = N), 1385 (C–O), 1315, 1140 (SO2), 960 (S–N), 845 (C–S), 439 (M–N), 523 (M–O)	28540	50.88 (50.96)	4.84 (4.52)	7.91 (8.22)

Figure 2 Proposed structure of the metal complex.

Table II.  Results of Antibacterial Bioassay (concentration used 1 mg/mL of DMSO).

	Compound
Bacteria	L1	L2	L3	L4	L5	1	2	3	4	5	6	7	8	9	10	11	12	SD
Gram-negative
(a)	16	18	20	21	23	23	24	24	26	24	25	25	26	27	26	27	28	30
(b)	10	08	09	10	11	10	11	10	12	10	11	11	13	14	13	15	15	27
(c)	14	15	15	16	18	17	17	18	19	20	18	19	20	19	18	19	21	26
(d)	13	15	16	16	17	18	17	18	19	18	17	18	20	19	19	20	22	27
(e)	17	15	18	19	19	19	18	19	20	19	20	20	21	22	20	22	25	30
(f)	13	12	13	15	16	16	15	17	18	17	17	18	20	18	19	21	26	28
Gram-positive
(g)	15	17	18	19	20	19	18	19	20	20	21	21	22	21	20	22	23	26
(h)	11	15	17	18	20	19	18	19	20	19	19	20	21	20	20	20	22	27
(j)	17	15	16	17	18	18	18	18	19	18	19	20	20	21	20	22	24	30
(k)	16	17	16	17	18	17	18	18	20	18	20	20	21	19	20	21	24	28

(a) = E. coli, (b) = K. pneumoniae, (c) = P. aeruginosa, (d) = P. mirabilis, (e) = S. typhi, (f) = S. dysenteriae, (g) = B. cereus, (h) = C. diphtheriae, (j) = S. aureus and (k) = S. pyogenes. < 10: weak; >10: moderate; > 16: Significant. SD = Standard Drug (Imipenum)

Figure 3 Comparison of Antibacterial Activity.

Figure 4 Comparison of Antifungal Activity.

Table III.  Results of Antifungal Bioassay (concentration used 200 μg/mL).

	Compound
Fungus	L1	L 2	L 3	L 4	L 5	1	2	3	4	5	6	7	8	9	10	11	12	SD
(a)	00	00	20	00	21	25	00	00	00	00	00	00	00	23	00	00	26	A
(b)	00	10	00	00	00	00	00	00	00	00	22	00	00	00	00	00	00	B
(c)	15	00	00	00	00	18	00	00	00	18	00	00	00	00	00	00	28	C
(d)	10	00	00	15	00	00	00	00	20	00	00	00	23	00	00	00	00	D
(e)	00	00	00	00	00	00	00	00	00	00	00	00	20	00	00	00	32	E
(f)	00	00	00	00	00	00	00	00	00	00	00	00	28	00	00	00	00	F

(a) = T. longifusus, (b) = C. albicans, (c) = A. flavus, (d) = M. canis, (e) = F. solani,(f) = C. Glaberata SD = Standard Drugs MIC μg/mL; A = Miconazole (70 μg/mL: 1.6822 × 10^{− 7} moles/mL), B = Miconazole (110.8 μg/mL: 2.6626 × 10^{− 7} moles/mL), C = Amphotericin B (20 μg/mL: 2.1642 × 10^{− 8} moles/mL), D = Miconazole (98.4 μg/mL: 2.3647 × 10^{− 7} moles/mL), E = Miconazole (73.25 μg/mL: 1.7603 × 10^{− 7} moles/mL), F = Miconazole (110.8 μg/mL: 2.66266 × 10^{− 7} moles/mL)

Table IV.  Results of Minimum Inhibitory Concentration (MIC) of Selected Compounds (4), (6), (7), (8), (9), (10), (11), and (12) against Selected Bacteria.

No.	12	14	15	16	17	18	19	20
Gram-negative
E. coli	3.834 × 10^− 8	3.686 × 10^− 8	7.425 × 10^− 8	3.676 × 10^− 8	1.425 × 10^− 7	7.079 × 10^− 8	3.564 × 10^− 8	1.412 × 10^− 8
P. aeruginosa	–	–	–	–	–	–	–	3.530 × 10^− 8
P. mirabilis	–	–	–	–	–	–	–	3.530 × 10^− 8
S. typhi	–	–	–	–	–	–	–	1.412 × 10^− 7
S. dysenteriae	–	–	–	–	–	–	–	7.061 × 10^− 8
Gram-positive
B. cereus	–	7.372 × 10^− 8	3.713 × 10^− 8	1.470 × 10^− 7	1.425 × 10^− 7	–	3.564 × 10^− 8	3.530 × 10^− 8
C. diphtheriae	–	–	–	–	–	–	–	1.412 × 10^− 8
S. pyogenes	–	–	–	–	–	–	–	1.412 × 10^− 7

Table V.  Brine Shrimp Bioassay Data of the Ligands (L₁)–(L₅) and their Metal (II) Complexes (1)–(12).

Compound	LD50 (Mm/ml)
L1	> 3.264 × 10^− 3
L2	> 2.991 × 10^− 3
L3	> 3.619 × 10^− 3
L4	> 3.444 × 10^− 3
L5	> 3.286 × 10^− 3
1	> 1.549 × 10^− 3
2	> 1.538 × 10^− 3
3	> 1.550 × 10^− 3
4	> 1.534 × 10^− 3
5	> 1.484 × 10^− 3
6	4.644 × 10^− 4
7	> 1.485 × 10^− 3
8	> 1.470 × 10^− 3
9	> 1.425 × 10^− 3
10	4.106 × 10^− 4
11	> 1.426 × 10^− 3
12	> 1.412 × 10^− 3

Table VI.  Selected Bond lengths [A] and Bond angles [deg] for (L₃).

Bond distances
S(1)–O(1)	1.436(2)	N(5)–H(64)	0.86(6)	C(15)–C(16)	1.384(6)	C(34)–C(35)	1.398(7)
S(1)–O(2)	1.438(3)	N(5)–H(62)	0.83(5)	C(15)–H(15A)	0.9500	C(34)–C(39)	1.401(7)
S(1)–N(1)	1.610(3)	N(6)–C(20)	1.276(6)	C(16)–C(17)	1.385(6)	C(35)–C(36)	1.375(7)
S(3)–O(10)	1.437(3)	C(1)–C(2)	1.384(6)	C(20)–H(20A)	0.9500	C(38)–H(38A)	0.9500
S(3)–N(5)	1.611(4)	C(2)–C(3)	1.386(6)	C(21)–C(22)	1.389(7)	C(40)–C(45)	1.386(6)
S(3)–C(27)	1.773(4)	C(2)–H(2C)	0.9500	C(21)–C(26)	1.409(7)	C(40)–C(41)	1.395(5)
S(4)–O(8)	1.435(3)	C(3)–C(4)	1.403(6)	C(22)–C(23)	1.381(7)	C(41)–C(42)	1.385(6)
S(4)–O(7)	1.436(3)	C(3)–H(3C)	0.9500	C(22)–H(22A)	0.9500	C(41)–H(41A)	0.9500
S(4)–N(7)	1.614(4)	C(4)–C(5)	1.390(6)	C(23)–C(24)	1.367(9)	C(42)–C(43)	1.380(6)
S(4)–C(40)	1.772(4)	C(5)–C(6)	1.381(6)	C(23)–H(23A)	0.9500	C(42)–H(42A)	0.9500
O(3)–C(13)	1.344(6)	C(5)–H(5D)	0.9500	C(24)–C(25)	1.385(8)	C(43)–C(44)	1.387(6)
O(3)–H(3)	0.8400	C(6)–H(6C)	0.9500	C(24)–H(24A)	0.9500	C(44)–C(45)	1.396(6)
O(12)–H(12)	0.8400	C(9)–H(9A)	0.9500	C(28)–H(28A)	0.9500	C(47)–C(52)	1.416(7)
N(3)–H(71)	0.75(6)	C(12)–H(12B)	0.9500	C(32)–H(32A)	0.9500	C(50)–H(50A)	0.9500
N(4)–C(33)	1.297(6)	C(14)–C(19)	1.376(5)	C(33)–C(34)	1.455(6)	C(51)–C(52)	1.402(6)
N(4)–C(30)	1.412(5)	C(14)–C(15)	1.386(6)	C(33)–H(33A)	0.9500	C(51)–H(51A)	0.9500
Bond Angles
O(1)–S(1)–O(2)	117.78(17)	C(2)–C(3)–C(4)	119.6(4)	N(6)–C(20)–C(21)	120.6(4)
O(1)–S(1)–N(1)	106.77(18)	C(2)–C(3)–H(3C)	120.2	N(6)–C(20)–H(20A)	119.7
O(2)–S(1)–N(1)	108.01(17)	C(4)–C(3)–H(3C)	120.2	C(21)–C(20)–H(20A)	119.7
O(1)–S(1)–C(1)	107.34(18)	C(5)–C(4)–C(3)	118.9(4)	C(22)–C(21)–C(26)	119.4(4)
O(2)–S(1)–C(1)	107.98(17)	C(5)–C(4)–N(2)	117.2(4)	C(22)–C(21)–C(20)	119.6(5)
O(4)–S(2)–C(14)	106.71(18)	C(1)–C(6)–C(5)	118.5(4)	C(24)–C(23)–C(22)	119.3(5)
O(5)–S(2)–C(14)	108.37(17)	C(1)–C(6)–H(6C)	120.8	C(24)–C(23)–H(23A)	120.3

Table VII.  Crystal data for 4-[(2-hydroxybenzene)- amino]benzenesulfonamide (L₃).

Identification code	shelxl
Formula weight	276.31
Temperature	173(2) K
Wavelength	0.71070 A
Crystal system, space group	Triclinic, P1
Unit cell dimensions	a = 8.9104(15) A alpha = 80.561(6) deg.
	b = 9.6705(15) A beta = 88.954(9) deg.
	c = 14.712(3) A gamma = 83.235(8) deg.
Volume	1241.9(4) A 3
Z, Calculated density	4, 1.478 Mg/m 3
Absorption coefficient	0.266 mm − 1
F(000)	576
Theta range for data collection	2.15 to 28.00 deg.
Limiting indices	− 11 < = h < = 11, − 12 < = k < = 12, − 19 < = l < = 19
Reflections collected / unique	24746 / 11393 [R(int) = 0.0466]
Completeness to theta = 28.00	99.7%
Max. and min. transmission	1.0000 and 0.7845
Refinement method Full-matrix least-squares on F 2
Data / restraints / parameters	11393 / 3 / 718
Goodness-of-fit on F 2	1.090
Final R indices [I > 2sigma(I)]	R1 = 0.0727, wR2 = 0.2028
R indices (all data)	R1 = 0.0824, wR2 = 0.2194
Absolute structure parameter	0.03(8)
Largest diff. peak and hole	1.265 and − 0.526 e.Â