Synthesis and characterization of a proton transfer salt between 2,6-pyridinedicarboxylic acid and 2-aminobenzothiazole, and its complexes and their inhibition studies on carbonic anhydrase isoenzymes

Figures & data

Figure 1. Syntheses of compounds 1–5: (a) for 1, (b) for 2–4 and (c) for 5.

Table 1. Crystal data and structure refinement details for compounds 2 and 5.

	2	5
Chemical formula	C21H21N4O12SFe	C14H11N3O5SCu
Formula weight	609.34	396.88
Temperature (K)	100(2)	115(2)
Wavelength (Å)	0.71073	0.71073
Crystal system, space group	Monoclinic, C2/c	Monoclinic, C2/c
Unit cell dimensions (Å, °)
a	18.9865(4)	25.8098(8)
b	10.4654(3)	7.2465(2)
c	25.7499(6)	18.5025(6)
β	97.287(2)	119.6660(10)
Volume (Å^3)	5075.2(2)	3006.95(16)
Z	8	8
Absorption coefficient (mm^1)	0.748	1.753
Calculated density (Mg m^−3)	1.595	1.623
F(000)	2504	1608
Crystal size (mm)	0.36 × 0.30 × 0.20	0.38 × 0.22 × 0.07
Theta range for data collection (°)	1.59–28.31	1.82–28.42
Limiting indices	−25 ≤ h ≤ 24, −13 ≤ k ≤ 13, −34 ≤ l ≤ 33	−32 ≤ h ≤ 34, −9 ≤ k ≤ 9, −24 ≤ l ≤ 15
Reflections collected	23 695	13 544
Independent reflections	6328	3789
Number of reflections used	4621	3085
Number of parameters	384	242
Max. and min. transmission	0.764, 0.861	0.658, 0.893
Refinement method	Full-matrix least-squares on F^2	Full-matrix least-squares on F^2
Final R indices [I ≥ 2σ(I)]	R1 = 0.0394, wR2 = 0.0999	R1 = 0.0345, wR2 = 0.0895
R indices (all data)	R1 = 0.0641, wR2 = 0.01175	R1 = 0.0478, wR2 = 0.1122
Goodness-of-fit on F^2	1.070	1.174
Largest difference in peak and hole (e Å^−3)	−0.370 and 0.319	−0.561 and 0.787

Figure 2. An ORTEP drawing of asymmetric unit of 2 with the atom-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level.

Figure 3. An ORTEP drawing of asymmetric unit of 5 with the atom-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level.

Table 2. Selected bond distances (Å) and angles (°) for compounds 2 and 5.

Compound 2
Fe1–O1	1.9961(15)	Fe1–O5	1.9994(18)	Fe1–N1	2.0562(17)
Fe1–O4	2.0746(15)	Fe1–O8	2.0180(16)	Fe1–N2	2.0470(16)
O1–Fe1–O4	151.13(6)	O4–Fe1–O5	94.02(6)	O5–Fe1–N1	99.14(7)
O1–Fe1–O5	94.62(7)	O4–Fe1–O8	91.25(6)	O5–Fe1–N2	76.24(7)
O1–Fe1–O8	94.10(7)	O5–Fe1–O8	151.59(7)	O8–Fe1–N1	109.18(7)
O1–Fe1–N1	76.68(7)	O4–Fe1–N1	74.77(6)	O8–Fe1–N2	75.98(7)
O1–Fe1–N2	120.03(7)	O4–Fe1–N2	88.79(6)	N1–Fe1–N2	162.68(7)
Compound 5
Cu1–N1	1.917(2)	Cu1–O1	2.033(2)	Cu1–O1W	2.257(2)
Cu1–N2	1.981(2)	Cu1–O4	2.047(2)
N1–Cu1–N2	162.79(10)	N2–Cu1–O4	96.19(9)	O1–Cu1–O1W	87.93(8)
N1–Cu1–O1	79.87(9)	O1–Cu1–O4	158.91(8)	O4–Cu1–O1W	97.05(8)
N2–Cu1–O1	103.58(9)	N1–Cu1–O1W	100.23(9)
N1–Cu1–O4	79.09(9)	N2–Cu1–O1W	96.76(9)

Table 3. Hydrogen bonding geometry of compounds 2 and 5 (Å, °).

D–H ··· A	d(D–H)	d(H ··· A)	d(D ··· A)	∠D–H ··· A
Compound 2
O2W–H2A–O4	0.808(17)	2.07(2)	2.858(2)	166(4)
Compound 5
N3–H3A–O4	0.88	2.03	2.742(3)	137.7

Table 4. ¹H-NMR chemical shifts (ppm) with coupling constants and assignments for compound 1.

H^5	7.01 (1H, t) [^3JH5-H4,6 = 7.51 Hz]
H^4	7.21 (1H, t) [^3JH4-H3,5 = 7.61 Hz]
H^6	7.33 (1H, d) [^3JH6-H5 = 7.95 Hz]
H^3	7.64 (1H, d) [^3JH3-H4 = 7.75 Hz]
H^8	7.91 (1H, t) [^3JH8-H7,9 = 7.67 Hz]
H^7, H^9	8.25 (2H, d) [^3JH7,9-H8 = 7.71 Hz]
H^1, H^2, H^10	Not observed

Table 5. IC₅₀ values of esterase activities on hCA I and hCA II isoenzymes.

	Esterase IC50 (mM)
Inhibitor	hCA I	hCA II
AAZ	6.1 × 10^−3	4.5 × 10^−3
H2dipic	No inhibition	No inhibition
Fedipic	No inhibition	No inhibition
Codipic	No inhibition	No inhibition
Nidipic	No inhibition	No inhibition
Cudipic	No inhibition	No inhibition
ABT	No inhibition	No inhibition
FeABT	0.284	0.257
CoABT	0.313	0.289
NiABT	0.337	0.287
CuABT	0.345	0.301
1	0.746	0.674
2	0.241	0.221
3	0.244	0.236
4	0.276	0.254
5	0.299	0.281