N. Alvarez, et al.
InorganicaChimicaActa508(2020)119622
Table 1
Crystal data and structure refinements Cu-BT and Cu-TT complexes.
Identification code
Cu-BT 298 K
Cu-BT 100 K
Cu-TT
Empirical formula
Formula weight
Temperature
C22H20Cl2Cu2N6O6S4
790.68
298(2) K
C22H20Cl2Cu2N6O6S4
790.68
100(2) K
C60H66Cl2Cu8F12N20O29P2S12
2785.20
100(2) K
Wavelength
0.71073 Å
0.71073 Å
1.54184 Å
Crystal system
Space group
Triclinic
P-1
Triclinic
P-1
Triclinic
P1
Unit cell dimensions
a = 11.1441(2) Å
b = 11.2582(2) Å
c = 13.0039(2) Å
α = 106.5400(10)°
β = 90.8690(10)°
γ = 102.6770(10)°
1520.60(5) Å3
2
a = 10.51(2) Å
b = 10.63(3) Å
c = 11.54(6) Å
α = 106.93(13)°
β = 91.86(10)°
a = 10.6888(3) Å
b = 14.6062(3) Å
c = 17.8915(5) Å
α = 71.1060(10)°
β = 82.4990(10)°
γ
= 102.47(8)°
γ = 70.1230(10)°
Volume
Z
Density (calculated)
Absorption coefficient
F(0 0 0)
Crystal size
Theta range for data collection
Index ranges
1198(7) Å3
2484.67(11) Å3
2
1
1.727 Mg/m3
1.897 mm−1
2.192 Mg/m3
1.861 Mg/m3
2.408 mm−1
5.930 mm−1
796
796
1394
0.482 × 0.109 × 0.102 mm3
3.001 to 25.073°
−12 ≤ h ≤ 13, −13 ≤ k ≤ 13,
−15 ≤ l ≤ 15
33,677
0.482 × 0.109 × 0.102 mm3
3.189 to 29.117°
−13 ≤ h ≤ 13, −13 ≤ k ≤ 13,
−15 ≤ l ≤ 15
24,509
0.092 × 0.070 × 0.051 mm3
2.611 to 74.652°
−13 ≤ h ≤ 13, −16 ≤ k ≤ 18, 0 ≤ l ≤ 22
Reflections collected
9919
Independent reflections
Completeness to
5363 [R(int) = 0.0605]
99.20%
5602 [R(int) = 0.0512]
99.70%
9919 [R(int) = 0.0492]
98.6%
theta = 25.242°
Absorption correction
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R indices (all data)
Semi-empirical from equivalents
0.995 and 0.750
5363/0/387
Semi-empirical from equivalents
0.918 and 0.786
5602/0/424
Semi-empirical from equivalents
0.7538 and 0.6086
9919/3/1336
1.040
1.031
1.037
R1 = 0.0491, wR2 = 0.1262
R1 = 0.0738, wR2 = 0.1443
0.732 and −0.756 e.Å−3
R1 = 0.0430, wR2 = 0.1105
R1 = 0.0579, wR2 = 0.1190
1.244 and −0.860 e.Å−3
R1 = 0.0514, wR2 = 0.1270
R1 = 0.0662, wR2 = 0.1352
1.048 and −0.651 e.Å−3
Largest diff. peak and hole
amide.
appeared and were washed with cold water and dried at room tem-
perature. Adequate single crystals for SCXRD were obtained in both
cases.
The stoichiometries of both complexes were: [Cu2Cl2(BT)2] and
[Cu4Cl(OH)2(TT)2H2O]PF6⋅3.5H2O.
Ethyl 2-(2-methylthiazole-4-carboxamido)thiazole-4-carboxylate (BT):
Compound BT was prepared following general procedure for amide
bond formation from 1b and 2a. Y = 90%. Solid. M.p. 166–169 °C.
Rf = 0.33 (EtOAc:hexane, 1:1),1H NMR (400 MHz, CDCl3) δ 1.43 (t,
J = 7.1 Hz, 3H), 2.75 (s, 3H), 4.44 (q, J = 7.1 Hz, 2H), 7.91 (s, 1H),
8.16 (s, 1H), 10,73 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 14.4, 19.2,
61.5, 122.5, 125.8, 142.2, 147.0, 157.3, 158.6, 161.5, 167.0. HRMS m/
zcalcd for C11H11N3NaO3S2 ([M + Na]+) 320.0134, found 320.0183.
IR film ν(cm−1) 3109, 2924, 1716, 1666, 1624, 1535, 1234, 1211,
1173, 1096.
2-(2-methylthiazole-4-carboxamido) thiazole-4-carboxylic acid (3):
Compound 3 was prepared following general procedure for ester hy-
drolisis from BT. The acid was employed without further purification.
Ethyl 2-(2-(2-methylthiazole-4-carboxamido)thiazole-4-carboxamido)
thiazole-4-carboxylate (TT): Compound TT was prepared following
general procedure for amide bond formation from 1b and 3. Y = 66%.
The analytic results were:
[Cu2(BT)2Cl2] (code Cu-BT): Yield: 25%. Anal. calcd.(%) for
C22H20Cl2Cu2N6O6S4.
C, 33,38; H, 2.62; N, 10.57; S,16.51.Calcd.: C, 33.44; H, 2.54; N,
10.63; S, 16.23. λmax(DMSO)(nm): 421 (sh)(dimeric structure) [41],
772. IR (KBr pellet, cm−1): 1701(s) (νas(C]O) amide),1684(sh) (νas(C]
O)ester), 1638(s) (νs(C]O) ester), 1631(s) (νs(C]O)amide).
[Cu4Cl(OH)2(TT)2H2O]PF6⋅3·.5H2O(code Cu-TT) Yield: 22%. Anal.
calcd. for C60H66Cl2Cu8F12N20O29P2S12
.
C, 25.58; H, 2.45; N, 10.03; S, 14.10 Calcd.:
C 25.85, H 2.37, N 10.05, S 13,79 λmax(DMSO)(nm): 726. IR (KBr
pellet, cm1):1712(m) (νas(C]O) amide),1622(s) (νs(C]O) ester) and (νs
(C]O)amide).
Solid.M.p. 225–229. Rf
=
0.34 (EtOAc: hexane, 2:1), 1H NMR
(400 MHz, CDCl3) δ 1.44 (t, J = 7.1 Hz, 3H), 2.86 (s, 3H), 4.45 (q,
J = 7.1 Hz, 2H), 7.92 (s, 1H), 8.04 (s, 1H), 8.22 (s, 1H), 10.41 (s, 1H),
10.54 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 14.4, 19.2, 61.4, 121.2,
122.5, 126.2, 142.1, 142.3 146.7, 157.3, 157.4, 158.5, 158.7, 161.4,
167.4. HRMS m/zcalcd for C15H13N5NaO4S3 ([M + Na]+) 446.0022,
found 446.0025. IR film ν(cm−1) 3421, 2928, 1624, 1539, 1230, 1092.
2.4. DNA binding constant: UV absorption titration experiments
The intrinsic binding constant (Kb) of the compounds to isolated
calf thymus DNA were determined using absorption titration mea-
surements and the Benesi-Hildebrand equation. In the latter the con-
stant is calculated as the slope to the intercept ratio of the [complex]/
Aobs as a function of 1/[DNA] plot [42–46]. In all cases the con-
centration of the complexes was kept constant at 10–15 μM in 5 mM
buffer Tris/HCl, pH = 7.5 and 50 mM of NaCl while adding Calf
Thymus-DNA (CT-DNA) to final concentrations 0 to 250 μM.
The stock solution of CT-DNA gave an absorbance at 260 to 280
ratio (A260/A280) of 1.8–1.9, consistent with the DNA being suffi-
ciently free of protein [46]. It was kept at 4 °C and used within 1 day.
DNA concentration was measured from the intensity of the 260 nm
2.3. Synthesis of copper complexes
Copper complexes with bi-thiazoles were obtained mixing metha-
nolic solutions containing 2.7 mg (0.01 mmol) of BT and 2.0 mg of
CuCl2·2H2O (0.01 mmol) for the synthesis of Cu-BT and 2.5 mg of TT
and 2 mg of CuCl2·2H2O for the synthesis of Cu-TT.
The resulting green solutions were stirred for 30 min at room
temperature and the solvent was slowly evaporated. Green crystals
3