Synthesis, X-ray structure, anti­microbial activity, DFT and mol­ecular docking studies of N-(thio­phen-2-ylmeth­yl)thio­phene-2-carboxamide

In the present study, N-(thio­phen-2-ylmeth­yl)thio­phene-2-carboxamide, C₁₀H₉NOS₂, (I), was obtained by the reaction of thio­phene-2-car­bon­yl chloride and thio­phen-2-ylmethanamine. Characterization of (I) was carried out using X-ray diffraction, spectroscopic techniques and elemental analyses. The DFT/B3LYP/6-311++G(d,p) theoretical level was successfully applied to calculate the optimized geometry and the local and global chemical activity parameters. The results obtained show good agreement between the experimental and theoretical geometrical parameters. The local and global chemical activity parameters were examined to determine the electrophilic and nucleophilic sites in (I). The natural bond orbital (NBO) analysis of (I) gives an efficient methodology for investigating the inter- and intra­molecular bonding, as well as giving a convenient basis for investigating charge transfer or conjugative inter­actions in mol­ecular systems. Also, the anti­microbial activity of (I) was investigated against eight microorganisms using the microdilution method and it is found to have an effective anti­bacterial activity. In addition, mol­ecular docking studies were calculated in order to understand the nature of the binding of (I) with a lung cancer protein (PDB entry 1x2j).

Computing details

Data collection: APEX3 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT2015 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2015 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: WinGX (Farrugia, 2012).

N-(Thiophen-2-ylmethyl)thiophene-2-carboxamide

Crystal data

C10H9NOS2	F(000) = 232
Mr = 223.30	Dx = 1.383 Mg m^−3
Monoclinic, Pc	Mo Kα radiation, λ = 0.71073 Å
a = 4.9916 (5) Å	Cell parameters from 7719 reflections
b = 10.8497 (12) Å	θ = 2.8–26.6°
c = 10.0075 (10) Å	µ = 0.46 mm^−1
β = 98.411 (3)°	T = 296 K
V = 536.15 (10) Å^3	Block, colourless
Z = 2	0.12 × 0.11 × 0.09 mm

Data collection

Bruker APEX-3 CCD diffractometer	Rint = 0.031
φ and ω scans	θmax = 28.3°, θmin = 2.8°
13633 measured reflections	h = −6→6
2441 independent reflections	k = −14→14
2124 reflections with I > 2σ(I)	l = −13→13

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.047	w = 1/[σ^2(Fo^2) + (0.0638P)^2 + 0.1304P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.119	(Δ/σ)max < 0.001
S = 1.03	Δρmax = 0.24 e Å^−3
2441 reflections	Δρmin = −0.20 e Å^−3
149 parameters	Absolute structure: Refined as a perfect inversion twin.
7 restraints

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refined as a 2-component perfect inversion twin.

Intensity data of (I) was collected on a D8-QUEST (Bruker APEX-II CCD) diffractometer at 296 K using graphite-monochromated Mo K_α radiation (λ = 0.71073 Å). Data collection and cell refinement were carried out using Bruker SAINT (Bruker, 2013) while data reduction was applied using Bruker SAINT (Bruker, 2013). The structure was solved by direct methods using SHELXT-2015 (Sheldrick, 2008) and refined with full-matrix least-squares calculations on F² using SHELXL2015 (Sheldrick, 2015) implemented in WinGX (Farrugia, 2012) program suit.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.9238 (10)	0.7704 (4)	0.4947 (5)	0.0675 (11)
H1	1.0457	0.8287	0.4716	0.081*
C2	0.8780 (11)	0.7495 (5)	0.6205 (5)	0.0737 (13)
H2	0.9655	0.7923	0.6948	0.088*
C3	0.6860 (9)	0.6572 (4)	0.6307 (4)	0.0557 (10)
H3	0.6326	0.6318	0.7116	0.067*
C4	0.5853 (7)	0.6085 (3)	0.5052 (3)	0.0387 (7)
C5	0.3895 (7)	0.5092 (3)	0.4662 (3)	0.0375 (7)
C6	0.0814 (8)	0.3565 (4)	0.5371 (4)	0.0504 (9)
H6A	−0.0184	0.3664	0.4470	0.060*
H6B	−0.0473	0.3605	0.6008	0.060*
O1	0.3367 (6)	0.4749 (3)	0.3476 (2)	0.0554 (7)
S1	0.7335 (2)	0.67812 (12)	0.38172 (11)	0.0690 (4)
N1	0.2752 (6)	0.4574 (3)	0.5645 (3)	0.0418 (6)
C7	0.2164 (7)	0.2326 (4)	0.5475 (4)	0.0486 (9)
C8	0.188 (7)	0.146 (3)	0.643 (4)	0.127 (13)	0.702 (8)
H8	0.0796	0.1545	0.7102	0.153*	0.702 (8)
C9	0.351 (5)	0.0412 (13)	0.624 (2)	0.120 (6)	0.702 (8)
H9	0.3742	−0.0244	0.6843	0.144*	0.702 (8)
C10	0.462 (2)	0.0454 (10)	0.517 (2)	0.113 (6)	0.702 (8)
H10	0.5541	−0.0206	0.4856	0.135*	0.702 (8)
S2	0.4233 (5)	0.1873 (2)	0.4381 (3)	0.0776 (9)	0.702 (8)
C8X	0.441 (6)	0.187 (2)	0.496 (3)	0.082 (2)	0.298 (8)
H8X	0.5339	0.2385	0.4433	0.098*	0.298 (8)
C9X	0.531 (7)	0.064 (3)	0.522 (3)	0.082 (2)	0.298 (8)
H9X	0.6675	0.0223	0.4860	0.098*	0.298 (8)
C10X	0.370 (8)	0.021 (3)	0.612 (4)	0.082 (2)	0.298 (8)
H10X	0.3648	−0.0608	0.6392	0.098*	0.298 (8)
S2X	0.193 (2)	0.1285 (15)	0.664 (2)	0.082 (2)	0.298 (8)
H1A	0.325 (13)	0.482 (6)	0.644 (4)	0.098*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.067 (3)	0.052 (2)	0.086 (3)	−0.008 (2)	0.021 (2)	0.007 (2)
C2	0.080 (3)	0.067 (3)	0.071 (3)	−0.016 (2)	0.000 (2)	−0.008 (2)
C3	0.065 (2)	0.060 (2)	0.042 (2)	−0.0154 (19)	0.0099 (17)	0.0031 (16)
C4	0.0455 (16)	0.0382 (15)	0.0343 (15)	0.0103 (13)	0.0121 (13)	0.0059 (12)
C5	0.0483 (19)	0.0369 (15)	0.0280 (13)	0.0106 (13)	0.0084 (12)	0.0007 (12)
C6	0.051 (2)	0.055 (2)	0.0463 (18)	−0.0054 (17)	0.0112 (16)	−0.0043 (15)
O1	0.0814 (19)	0.0613 (16)	0.0244 (10)	−0.0016 (13)	0.0112 (11)	−0.0044 (10)
S1	0.0889 (8)	0.0727 (7)	0.0507 (6)	−0.0142 (6)	0.0280 (5)	0.0080 (5)
N1	0.0587 (17)	0.0426 (15)	0.0252 (12)	−0.0015 (12)	0.0095 (11)	−0.0044 (10)
C7	0.051 (2)	0.0471 (19)	0.0458 (18)	−0.0148 (16)	0.0012 (15)	0.0005 (15)
C8	0.18 (2)	0.091 (17)	0.112 (19)	−0.035 (12)	0.037 (13)	−0.002 (12)
C9	0.190 (15)	0.048 (6)	0.101 (9)	−0.019 (7)	−0.048 (9)	0.013 (6)
C10	0.077 (7)	0.046 (5)	0.201 (14)	0.015 (5)	−0.028 (9)	−0.038 (7)
S2	0.0907 (15)	0.0559 (11)	0.0909 (15)	0.0208 (9)	0.0294 (13)	0.0055 (11)
C8X	0.096 (5)	0.060 (4)	0.091 (5)	−0.011 (3)	0.016 (3)	0.017 (3)
C9X	0.096 (5)	0.060 (4)	0.091 (5)	−0.011 (3)	0.016 (3)	0.017 (3)
C10X	0.096 (5)	0.060 (4)	0.091 (5)	−0.011 (3)	0.016 (3)	0.017 (3)
S2X	0.096 (5)	0.060 (4)	0.091 (5)	−0.011 (3)	0.016 (3)	0.017 (3)

Geometric parameters (Å, º)

C1—C2	1.331 (7)	C7—C8	1.36 (3)
C1—S1	1.694 (5)	C7—C8X	1.39 (3)
C1—H1	0.9300	C7—S2X	1.640 (18)
C2—C3	1.400 (6)	C7—S2	1.685 (5)
C2—H2	0.9300	C8—C9	1.43 (3)
C3—C4	1.388 (5)	C8—H8	0.9300
C3—H3	0.9300	C9—C10	1.27 (2)
C4—C5	1.468 (5)	C9—H9	0.9300
C4—S1	1.707 (3)	C10—S2	1.730 (16)
C5—O1	1.235 (4)	C10—H10	0.9300
C5—N1	1.331 (4)	C8X—C9X	1.42 (4)
C6—N1	1.460 (5)	C8X—H8X	0.9300
C6—C7	1.501 (6)	C9X—C10X	1.38 (3)
C6—H6A	0.9700	C9X—H9X	0.9300
C6—H6B	0.9700	C10X—S2X	1.60 (3)
N1—H1A	0.84 (3)	C10X—H10X	0.9300
C2—C1—S1	111.9 (4)	C8X—C7—C6	131.9 (11)
C2—C1—H1	124.0	C8X—C7—S2X	99.6 (12)
S1—C1—H1	124.0	C6—C7—S2X	126.1 (6)
C1—C2—C3	113.9 (4)	C8—C7—S2	113.0 (16)
C1—C2—H2	123.0	C6—C7—S2	121.9 (3)
C3—C2—H2	123.0	C7—C8—C9	110 (3)
C4—C3—C2	111.6 (4)	C7—C8—H8	125.1
C4—C3—H3	124.2	C9—C8—H8	125.1
C2—C3—H3	124.2	C10—C9—C8	114.1 (18)
C3—C4—C5	131.2 (3)	C10—C9—H9	123.0
C3—C4—S1	110.4 (3)	C8—C9—H9	123.0
C5—C4—S1	118.3 (2)	C9—C10—S2	112.5 (12)
O1—C5—N1	121.9 (3)	C9—C10—H10	123.8
O1—C5—C4	121.1 (3)	S2—C10—H10	123.8
N1—C5—C4	117.0 (3)	C7—S2—C10	90.0 (6)
N1—C6—C7	112.3 (3)	C7—C8X—C9X	121 (2)
N1—C6—H6A	109.1	C7—C8X—H8X	119.6
C7—C6—H6A	109.1	C9X—C8X—H8X	119.6
N1—C6—H6B	109.1	C10X—C9X—C8X	104 (3)
C7—C6—H6B	109.1	C10X—C9X—H9X	128.1
H6A—C6—H6B	107.9	C8X—C9X—H9X	128.1
C1—S1—C4	92.2 (2)	C9X—C10X—S2X	112 (3)
C5—N1—C6	121.4 (3)	C9X—C10X—H10X	124.1
C5—N1—H1A	118 (5)	S2X—C10X—H10X	124.1
C6—N1—H1A	121 (5)	C10X—S2X—C7	99.9 (16)
C8—C7—C6	125.1 (16)
S1—C1—C2—C3	0.1 (6)	S2X—C7—C8—C9	−56 (66)
C1—C2—C3—C4	−0.3 (6)	S2—C7—C8—C9	1 (3)
C2—C3—C4—C5	178.1 (4)	C7—C8—C9—C10	−7 (3)
C2—C3—C4—S1	0.3 (5)	C8—C9—C10—S2	9 (3)
C3—C4—C5—O1	−176.1 (4)	C8—C7—S2—C10	2.6 (16)
S1—C4—C5—O1	1.5 (4)	C8X—C7—S2—C10	54 (3)
C3—C4—C5—N1	3.0 (5)	C6—C7—S2—C10	−177.5 (5)
S1—C4—C5—N1	−179.4 (2)	S2X—C7—S2—C10	4.3 (7)
C2—C1—S1—C4	0.1 (4)	C9—C10—S2—C7	−6.6 (13)
C3—C4—S1—C1	−0.2 (3)	C8—C7—C8X—C9X	16 (3)
C5—C4—S1—C1	−178.3 (3)	C6—C7—C8X—C9X	179.4 (13)
O1—C5—N1—C6	0.2 (5)	S2X—C7—C8X—C9X	16.8 (19)
C4—C5—N1—C6	−178.9 (3)	S2—C7—C8X—C9X	−117 (4)
C7—C6—N1—C5	89.6 (4)	C7—C8X—C9X—C10X	−6 (3)
N1—C6—C7—C8	113.3 (19)	C8X—C9X—C10X—S2X	−9 (3)
N1—C6—C7—C8X	−47.2 (15)	C9X—C10X—S2X—C7	17 (3)
N1—C6—C7—S2X	111.4 (7)	C8—C7—S2X—C10X	119 (68)
N1—C6—C7—S2	−66.6 (4)	C8X—C7—S2X—C10X	−18 (2)
C8X—C7—C8—C9	−13 (3)	C6—C7—S2X—C10X	177.7 (17)
C6—C7—C8—C9	−178.5 (13)	S2—C7—S2X—C10X	−4.1 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O1^i	0.93	2.44	3.304 (5)	154
N1—H1A···O1^i	0.84 (3)	2.08 (3)	2.899 (3)	163 (6)

Symmetry code: (i) x, −y+1, z+1/2.