Synthesis and characterization of some metal complexes of a proton transfer salt, and their inhibition studies on carbonic anhydrase isozymes and the evaluation of the results by statistical analysis

Figures & data

Figure 1. Syntheses of compounds 1–5.

Table 1. Crystal data and structure refinement details for compound 4.

	4
Empirical formula	C30H26N6O11S2Ni
Formula weight	769.40
T[K]	293(2)
Wavelength (Å)	0.71073
Crystal system, space group	Triclinic, P
Unit cell dimensions (Å, °)
a	10.168(3)
b	10.605(5)
c	15.979(4)
α	93.947(5)
β	104.405(6)
γ	110.375(4)
V (Å^3)	1541.4(9)
Z	2
Absorbtion coefficient (mm^−^1)	0.840
Dcalc (Mg/m^3)	1.658
F(000)	792
Crystal dimensions (mm)	0.25 × 0.18 × 0.07
θ range for data collection (°)	1.34–28.37
Index ranges	−12 ≤ h ≤ 13
	−14 ≤ k ≤ 14
	−21 ≤ l ≤ 21
Reflections collected	28 602
Independent reflections	7715 [Rint = 0.0310]
Data/parameters	6403/472
Max. and min. transmission	0.834, 0.943
Final R indices [I ≥ 2σ(I)]	R1 = 0.0348
	wR2 = 0.0764
R indices (all data)	R1 = 0.0462
	wR2 = 0.0869
Goodness-of-fit on F^2	1.055
Largest difference in peak and hole (e Å^−3)	0.944/−0.949

Figure 2. An ORTEP drawing of asymmetric unit of 4 with the atom-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level.

Table 2. Selected bond distances [Å] and angles [°] of compound 4.

Compound 4 (HMeOABT)2[Ni(DPC)2]·H2O
Ni1–O1	2.1698(17)	Ni–O5	2.1210(17)	Ni1–N1	1.9671(17)
Ni1–O4	2.1524(18)	Ni1–O8	2.1328(16)	Ni1–N2	1.9763(17)
O1–Ni1–O4	155.25(5)	O4–Ni1–O8	90.33(5)	O5–Ni1–N2	77.91(6)
O1–Ni1–O5	91.13(5)	O2–Ni1–N2	101.47(6)	O8–Ni1–N1	105.38(6)
O1–Ni1–N2	103.28(6)	O5–Ni1–O8	155.40(5)	N1–Ni1–N2	177.01(6)

Table 3. ¹H-NMR chemical shifts (ppm) with coupling constants and assignments for compound 1.

H5	3.72 (3H, s)
H4	6.81 (1H, d) [^3JH4-H3 = 8.50, ^4JH4-H6 = 2.50 Hz]
H3	7.23 (1H, d) [^3JH3-H4 = 9.00 Hz]
H6	7.29 (1H, d) [^4JH6-H4 = 2.50 Hz]
H8	8.18 (1H, t) [^3JH8-H7,9 = 7. 00 Hz]
H7, H9	8.26 (2H, d) [^3JH7,9-H8 = 7.50 Hz]
H^1, H^2, H^10	Not observed

Table 4. IC₅₀ values of newly synthesized compounds on the esterase activities of hCA I and hCA II isozymes.

	Esterase IC50*,† (mM)
Inhibitor	hCA I	hCA II
AAZ	4.33.10^−3 ± 0.00004	3.24.10^−3 ± 0.00005
H2DPC	No ınhibition	No ınhibition
FeDPC	No ınhibition	No ınhibition
CoDPC	No ınhibition	No ınhibition
NiDPC	No ınhibition	No ınhibition
CuDPC	No ınhibition	No ınhibition
MeOABT	0.800 ± 0.003	0.754 ± 0.003
FeMeOABT	0.332 ± 0.005	0.303 ± 0.001
CoMeOABT	0.309 ± 0.006	0.280 ± 0.004
NiMeOABT	0.305 ± 0.001	0.238 ± 0.009
CuMeOABT	0.356 ± 0.008	0.330 ± 0.007
1	0.512 ± 0.004	0.493 ± 0.002
2	0.193 ± 0.002	0.174 ± 0.004
3	0.224 ± 0.002	0.196 ± 0.006
4	0.237 ± 0.003	0.214 ± 0.002
5	0.242 ± 0.006	0.199 ± 0.005

AAZ was used as reference compound.

*Mean ± standard error, from three different assays.

†p < 0.0001 for all analysis.