Synthesis, spectroscopic investigation, crystal structure analysis, quantum chemical study, biological activity and mol­ecular docking of three isatin derivatives

Bargavi, S.; Gouthaman, S.; Sugunalakshmi, M.; Lakshmi, S.

doi:10.1107/S2053229621004940

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Synthesis, spectroscopic investigation, crystal structure analysis, quantum chemical study, biological activity and molecular docking of three isatin derivatives

S. Bargavi, S. Gouthaman, M. Sugunalakshmi and S. Lakshmi

Three isatin derivatives, namely, 1-allyl-3-hydroxy-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C₁₇H₁₇NO₃, 1-ethyl-3-hydroxy-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C₁₆H₁₇NO₃, and 5-bromo-3-hydroxy-1-methyl-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C₁₅H₁₄BrNO₃, were synthesized, crystallized by the slow-evaporation technique, characterized by ¹H and ¹³C NMR spectroscopy, and analysed by the single-crystal X-ray diffraction (XRD) method. Quantum chemical parameters, such as the energy of the highest occupied molecular orbital, energy of the lowest unoccupied molecular orbital, energy gap, electronic energy, ionization potential, chemical potential, global hardness, global softness and electrophilicity index, were calculated. The druglikeness and bioactivity scores of the compounds were calculated. The activities of these isatin derivatives against bacterial strains, such as Eschericia coli, Proteus vulgaris, Shigella flexneri, Staphylococcus aureus and Micrococcus luteus, and the fungal strain Aspergillus niger, were determined using the well-diffusion assay method. Molecular docking studies were carried out to predict the binding mode of the isatin compounds with the penicillin binding protein enzyme and to identify the interactions between the enzyme and the ligands under study.

Keywords: isatin derivatives; spectroscopy; crystal structure; quantum chemical calculations; druglikeness; bioactivity score; antimicrobial; molecular docking.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229621004940/ef3014sup1.cif Contains datablocks I_shelx, II_shelx, III_shelx, global
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229621004940/ef3014I_shelxsup2.hkl Contains datablock I_shelx
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229621004940/ef3014II_shelxsup3.hkl Contains datablock II_shelx
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229621004940/ef3014III_shelxsup4.hkl Contains datablock III_shelx
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229621004940/ef3014I_shelxsup5.cml Supplementary material
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229621004940/ef3014II_shelxsup6.cml Supplementary material
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229621004940/ef3014III_shelxsup7.cml Supplementary material

CCDC references: 1828486; 1828014; 1828286

Computing details top

For all structures, data collection: APEX2 (Bruker, 2008); cell refinement: APEX2 and SAINT (Bruker, 2008); data reduction: SAINT and XPREP (Bruker, 2008); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 (Farrugia, 2012) and PLATON (Spek, 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

3-Hydroxy-3-(6-oxocyclohex-1-en-1-yl)-1-(prop-2-en-1-yl)indol-2-one (I_shelx) top

Crystal data top

C₁₇H₁₇NO₃	F(000) = 600
M_r = 283.31	D_x = 1.322 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.6750 (7) Å	Cell parameters from 2006 reflections
b = 8.6138 (5) Å	θ = 2.9–25.0°
c = 14.1504 (8) Å	µ = 0.09 mm⁻¹
β = 90.075 (2)°	T = 296 K
V = 1423.05 (14) Å³	Block, colourless
Z = 4	0.30 × 0.25 × 0.20 mm

Data collection top

Bruker Kappa APEXII CCD diffractometer	2006 reflections with I > 2σ(I)
ω and φ scan	R_int = 0.038
Absorption correction: multi-scan (SADABS; Bruker, 2008)	θ_max = 25.0°, θ_min = 2.9°
T_min = 0.547, T_max = 0.746	h = −13→13
25650 measured reflections	k = −10→10
2492 independent reflections	l = −16→16

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.051	H-atom parameters constrained
wR(F²) = 0.135	w = 1/[σ²(F_o²) + (0.0497P)² + 1.0412P] where P = (F_o² + 2F_c²)/3
S = 1.13	(Δ/σ)_max < 0.001
2492 reflections	Δρ_max = 0.34 e Å⁻³
200 parameters	Δρ_min = −0.35 e Å⁻³
0 restraints

Special details top

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

Refinement. IS1

Alert level G

PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ············.. 1 Report

The H atom on the O2 hydroxy group was fixed at the calculated position and refined using a riding model with respect to its parent atom, with U_iso(H) = 1.5U_eq(O).

The terminal carbon atom (C17)of the allyl group was disordered over two positions with an occupancy ratio of 77:23.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
C17	0.4443 (3)	0.3678 (5)	0.1214 (3)	0.0569 (13)	0.774 (9)
H17A	0.383299	0.336357	0.158963	0.068*	0.774 (9)
H17B	0.458960	0.317257	0.064566	0.068*	0.774 (9)
C17'	0.5389 (15)	0.3786 (16)	0.0988 (11)	0.073 (5)	0.226 (9)
H17C	0.599696	0.316962	0.118723	0.088*	0.226 (9)
H17D	0.505572	0.361613	0.039953	0.088*	0.226 (9)
O2	0.29807 (13)	0.57697 (18)	0.50335 (10)	0.0396 (4)
H2	0.333707	0.528897	0.543855	0.059*
O1	0.25038 (14)	0.24387 (19)	0.28918 (10)	0.0433 (4)
O3	0.48480 (12)	0.39949 (18)	0.40727 (11)	0.0410 (4)
N1	0.40062 (15)	0.5493 (2)	0.29226 (12)	0.0350 (4)
C8	0.21765 (18)	0.5725 (2)	0.34877 (14)	0.0324 (5)
C7	0.28373 (17)	0.4819 (2)	0.42217 (13)	0.0295 (4)
C1	0.21858 (17)	0.2127 (2)	0.36904 (14)	0.0316 (5)
C6	0.23232 (16)	0.3253 (2)	0.44683 (13)	0.0300 (5)
C14	0.40240 (17)	0.4671 (2)	0.37351 (14)	0.0308 (5)
C13	0.29131 (19)	0.6134 (2)	0.27556 (15)	0.0349 (5)
C5	0.19747 (19)	0.2887 (3)	0.53363 (15)	0.0398 (5)
H5	0.204474	0.363648	0.580599	0.048*
C2	0.1618 (2)	0.0607 (3)	0.39103 (16)	0.0464 (6)
H2A	0.191153	−0.018213	0.348555	0.056*
H2B	0.080123	0.070244	0.379731	0.056*
C3	0.1811 (2)	0.0089 (3)	0.49190 (16)	0.0461 (6)
H3A	0.135971	−0.083448	0.504365	0.055*
H3B	0.261189	−0.017272	0.500783	0.055*
C9	0.1052 (2)	0.6184 (3)	0.34597 (17)	0.0425 (6)
H9	0.054779	0.590429	0.393823	0.051*
C11	0.1425 (3)	0.7494 (3)	0.19900 (18)	0.0556 (7)
H11	0.116018	0.810111	0.149202	0.067*
C4	0.1478 (2)	0.1349 (3)	0.56037 (17)	0.0470 (6)
H4A	0.064995	0.143126	0.562300	0.056*
H4B	0.174163	0.106951	0.623154	0.056*
C12	0.2561 (2)	0.7025 (3)	0.20011 (16)	0.0473 (6)
H12	0.306286	0.730021	0.151986	0.057*
C10	0.0683 (2)	0.7082 (3)	0.26962 (19)	0.0530 (7)
H10	−0.007651	0.740487	0.266694	0.064*
C15	0.5000 (2)	0.5719 (3)	0.23170 (18)	0.0519 (7)
H15A	0.568364	0.552388	0.268897	0.062*
H15B	0.502013	0.679859	0.212372	0.062*
C16	0.5051 (3)	0.4749 (4)	0.1465 (2)	0.0753 (9)
H16	0.564230	0.499286	0.105136	0.090*	0.774 (9)
H16'	0.446238	0.516368	0.110073	0.090*	0.226 (9)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C17	0.052 (3)	0.070 (3)	0.049 (2)	0.0023 (19)	0.0018 (17)	−0.0017 (18)
C17'	0.089 (13)	0.060 (9)	0.071 (9)	−0.001 (7)	0.040 (8)	−0.012 (7)
O2	0.0435 (9)	0.0422 (9)	0.0332 (8)	0.0048 (7)	−0.0038 (6)	−0.0122 (6)
O1	0.0539 (10)	0.0439 (9)	0.0323 (8)	−0.0099 (7)	0.0047 (7)	−0.0038 (7)
O3	0.0318 (8)	0.0457 (9)	0.0456 (9)	0.0038 (7)	−0.0053 (7)	−0.0086 (7)
N1	0.0324 (10)	0.0364 (10)	0.0363 (9)	−0.0081 (8)	0.0043 (7)	−0.0011 (8)
C8	0.0362 (11)	0.0270 (10)	0.0340 (11)	−0.0015 (9)	−0.0025 (9)	−0.0062 (8)
C7	0.0308 (10)	0.0298 (10)	0.0278 (10)	−0.0005 (8)	−0.0006 (8)	−0.0056 (8)
C1	0.0279 (11)	0.0351 (11)	0.0318 (11)	−0.0024 (8)	−0.0022 (8)	0.0003 (9)
C6	0.0246 (10)	0.0347 (11)	0.0306 (10)	0.0018 (8)	0.0003 (8)	0.0004 (8)
C14	0.0306 (11)	0.0294 (10)	0.0324 (10)	−0.0046 (8)	−0.0031 (8)	−0.0090 (8)
C13	0.0413 (12)	0.0265 (10)	0.0368 (11)	−0.0044 (9)	−0.0046 (9)	−0.0034 (9)
C5	0.0409 (13)	0.0444 (13)	0.0341 (11)	0.0010 (10)	0.0053 (9)	−0.0015 (10)
C2	0.0543 (15)	0.0410 (13)	0.0440 (13)	−0.0158 (11)	−0.0064 (11)	0.0028 (10)
C3	0.0512 (14)	0.0400 (13)	0.0471 (13)	−0.0094 (11)	−0.0014 (11)	0.0092 (11)
C9	0.0378 (12)	0.0436 (13)	0.0460 (13)	0.0064 (10)	−0.0054 (10)	−0.0104 (10)
C11	0.086 (2)	0.0381 (13)	0.0432 (13)	0.0128 (13)	−0.0223 (14)	−0.0030 (11)
C4	0.0470 (14)	0.0533 (15)	0.0407 (12)	−0.0036 (11)	0.0091 (10)	0.0093 (11)
C12	0.0692 (17)	0.0344 (12)	0.0383 (12)	−0.0035 (11)	−0.0054 (11)	0.0024 (10)
C10	0.0520 (15)	0.0499 (15)	0.0571 (15)	0.0181 (12)	−0.0228 (12)	−0.0150 (12)
C15	0.0468 (14)	0.0571 (16)	0.0519 (15)	−0.0126 (12)	0.0172 (11)	0.0011 (12)
C16	0.089 (2)	0.084 (2)	0.0539 (17)	0.001 (2)	0.0196 (16)	−0.0069 (17)

Geometric parameters (Å, º) top

C17—C16	1.217 (5)	C5—C4	1.495 (3)
C17—H17A	0.9300	C5—H5	0.9300
C17—H17B	0.9300	C2—C3	1.512 (3)
C17'—C16	1.141 (13)	C2—H2A	0.9700
C17'—H17C	0.9300	C2—H2B	0.9700
C17'—H17D	0.9300	C3—C4	1.506 (3)
O2—C7	1.420 (2)	C3—H3A	0.9700
O2—H2	0.8200	C3—H3B	0.9700
O1—C1	1.220 (2)	C9—C10	1.397 (3)
O3—C14	1.221 (3)	C9—H9	0.9300
N1—C14	1.350 (3)	C11—C10	1.370 (4)
N1—C13	1.410 (3)	C11—C12	1.387 (4)
N1—C15	1.456 (3)	C11—H11	0.9300
C8—C9	1.371 (3)	C4—H4A	0.9700
C8—C13	1.392 (3)	C4—H4B	0.9700
C8—C7	1.510 (3)	C12—H12	0.9300
C7—C6	1.517 (3)	C10—H10	0.9300
C7—C14	1.553 (3)	C15—C16	1.467 (4)
C1—C6	1.476 (3)	C15—H15A	0.9700
C1—C2	1.501 (3)	C15—H15B	0.9700
C6—C5	1.332 (3)	C16—H16	0.9300
C13—C12	1.378 (3)	C16—H16'	0.9300

C16—C17—H17A	120.0	C3—C2—H2B	109.0
C16—C17—H17B	120.0	H2A—C2—H2B	107.8
H17A—C17—H17B	120.0	C4—C3—C2	110.9 (2)
C16—C17'—H17C	120.0	C4—C3—H3A	109.5
C16—C17'—H17D	120.0	C2—C3—H3A	109.5
H17C—C17'—H17D	120.0	C4—C3—H3B	109.5
C7—O2—H2	109.5	C2—C3—H3B	109.5
C14—N1—C13	111.15 (17)	H3A—C3—H3B	108.1
C14—N1—C15	124.0 (2)	C8—C9—C10	118.5 (2)
C13—N1—C15	124.81 (19)	C8—C9—H9	120.8
C9—C8—C13	119.8 (2)	C10—C9—H9	120.8
C9—C8—C7	131.1 (2)	C10—C11—C12	121.5 (2)
C13—C8—C7	109.08 (18)	C10—C11—H11	119.3
O2—C7—C8	108.55 (16)	C12—C11—H11	119.3
O2—C7—C6	111.89 (16)	C5—C4—C3	112.05 (18)
C8—C7—C6	114.55 (16)	C5—C4—H4A	109.2
O2—C7—C14	107.55 (15)	C3—C4—H4A	109.2
C8—C7—C14	101.10 (16)	C5—C4—H4B	109.2
C6—C7—C14	112.49 (16)	C3—C4—H4B	109.2
O1—C1—C6	120.88 (19)	H4A—C4—H4B	107.9
O1—C1—C2	121.29 (19)	C13—C12—C11	117.1 (2)
C6—C1—C2	117.81 (18)	C13—C12—H12	121.4
C5—C6—C1	119.9 (2)	C11—C12—H12	121.4
C5—C6—C7	122.94 (19)	C11—C10—C9	120.8 (2)
C1—C6—C7	117.10 (16)	C11—C10—H10	119.6
O3—C14—N1	126.47 (19)	C9—C10—H10	119.6
O3—C14—C7	124.63 (18)	N1—C15—C16	116.1 (2)
N1—C14—C7	108.77 (17)	N1—C15—H15A	108.3
C12—C13—C8	122.2 (2)	C16—C15—H15A	108.3
C12—C13—N1	128.1 (2)	N1—C15—H15B	108.3
C8—C13—N1	109.64 (18)	C16—C15—H15B	108.3
C6—C5—C4	124.2 (2)	H15A—C15—H15B	107.4
C6—C5—H5	117.9	C17'—C16—C15	156.2 (10)
C4—C5—H5	117.9	C17—C16—C15	130.4 (3)
C1—C2—C3	112.82 (18)	C17—C16—H16	114.8
C1—C2—H2A	109.0	C15—C16—H16	114.8
C3—C2—H2A	109.0	C17'—C16—H16'	101.9
C1—C2—H2B	109.0	C15—C16—H16'	101.9

C9—C8—C7—O2	−70.4 (3)	C9—C8—C13—C12	1.5 (3)
C13—C8—C7—O2	108.18 (18)	C7—C8—C13—C12	−177.25 (19)
C9—C8—C7—C6	55.5 (3)	C9—C8—C13—N1	−178.09 (18)
C13—C8—C7—C6	−125.98 (18)	C7—C8—C13—N1	3.2 (2)
C9—C8—C7—C14	176.7 (2)	C14—N1—C13—C12	−179.4 (2)
C13—C8—C7—C14	−4.8 (2)	C15—N1—C13—C12	2.3 (3)
O1—C1—C6—C5	−179.7 (2)	C14—N1—C13—C8	0.2 (2)
C2—C1—C6—C5	1.7 (3)	C15—N1—C13—C8	−178.17 (19)
O1—C1—C6—C7	1.9 (3)	C1—C6—C5—C4	2.5 (3)
C2—C1—C6—C7	−176.61 (18)	C7—C6—C5—C4	−179.2 (2)
O2—C7—C6—C5	4.7 (3)	O1—C1—C2—C3	151.6 (2)
C8—C7—C6—C5	−119.3 (2)	C6—C1—C2—C3	−29.9 (3)
C14—C7—C6—C5	125.9 (2)	C1—C2—C3—C4	52.9 (3)
O2—C7—C6—C1	−176.97 (16)	C13—C8—C9—C10	−1.1 (3)
C8—C7—C6—C1	58.9 (2)	C7—C8—C9—C10	177.3 (2)
C14—C7—C6—C1	−55.8 (2)	C6—C5—C4—C3	21.6 (3)
C13—N1—C14—O3	−179.25 (19)	C2—C3—C4—C5	−48.2 (3)
C15—N1—C14—O3	−0.9 (3)	C8—C13—C12—C11	−0.7 (3)
C13—N1—C14—C7	−3.4 (2)	N1—C13—C12—C11	178.7 (2)
C15—N1—C14—C7	175.00 (19)	C10—C11—C12—C13	−0.3 (4)
O2—C7—C14—O3	67.2 (2)	C12—C11—C10—C9	0.6 (4)
C8—C7—C14—O3	−179.13 (19)	C8—C9—C10—C11	0.1 (4)
C6—C7—C14—O3	−56.5 (3)	C14—N1—C15—C16	101.9 (3)
O2—C7—C14—N1	−108.81 (18)	C13—N1—C15—C16	−79.9 (3)
C8—C7—C14—N1	4.9 (2)	N1—C15—C16—C17'	−110.1 (19)
C6—C7—C14—N1	127.54 (17)	N1—C15—C16—C17	−7.2 (6)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3ⁱ	0.82	2.31	2.839 (2)	123
C15—H15B···O3ⁱⁱ	0.97	2.54	3.444 (3)	155

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, y+1/2, −z+1/2.

1-Ethyl-3-hydroxy-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one (II_shelx) top

Crystal data top

C₁₆H₁₇NO₃	F(000) = 576
M_r = 271.30	D_x = 1.248 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 8.9227 (6) Å	Cell parameters from 1892 reflections
b = 12.8741 (6) Å	θ = 2.3–26.3°
c = 12.5994 (8) Å	µ = 0.09 mm⁻¹
β = 93.897 (3)°	T = 296 K
V = 1443.97 (15) Å³	Block, colourless
Z = 4	0.35 × 0.30 × 0.25 mm

Data collection top

Bruker Kappa APEXII CCD diffractometer	1892 reflections with I > 2σ(I)
ω and φ scan	R_int = 0.036
Absorption correction: multi-scan (SADABS; Bruker, 2008)	θ_max = 26.0°, θ_min = 2.3°
T_min = 0.716, T_max = 0.746	h = −11→9
19991 measured reflections	k = −15→15
2837 independent reflections	l = −15→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.045	H-atom parameters constrained
wR(F²) = 0.118	w = 1/[σ²(F_o²) + (0.0455P)² + 0.4767P] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max < 0.001
2837 reflections	Δρ_max = 0.16 e Å⁻³
210 parameters	Δρ_min = −0.15 e Å⁻³
77 restraints

Special details top

Refinement. IS2

Alert level G

1. PLAT002_ALERT_2_G Number of Distance or Angle Restraints on AtSite 8 Note

Atoms C2, C3, C4 of cyclohexenone moiety are disordered over two positions. The disordered positions were located from difference electron density peaks and refined with a target C-C distance of 1.52 Å using DFIX instruction.

2. PLAT003_ALERT_2_G Number of Uiso or Uij Restrained non-H Atoms ··· 6 Report

The thermal parameters of atoms in the disordered group are restrained with an effective standard deviation of 0.02 Å² to have the same Uij components.

3. PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ············.. 1 Report

The hydrogen on hydroxy group was fixed at calculated position and refined as a riding model with respect to its parent atom with U_iso(H) = 1.5U_eq(O).

4. PLAT172_ALERT_4_G The CIF-Embedded .res File Contains DFIX Records 2 Report

The atoms C2, C3, C4 of cyclohexenone moiety is disordered over two positions. The disordered positions were located from difference electron density peaks and refined with a target C—C distance of 1.52 Å using DFIX instruction.

5. PLAT177_ALERT_4_G The CIF-Embedded .res File Contains DELU Records 2 Report

The components of the anisotropic displacement parameters in the direction of the bond of disordered atoms are restrained to be equal within an effective standard deviation of 0.01 using DELU instruction.

6. PLAT178_ALERT_4_G The CIF-Embedded .res File Contains SIMU Records 1 Report

The atoms (C2, C3, C4) in the disordered group are restrained with an effective standard deviation of 0.02 Å² to have the same U^ij components using the SIMU instruction.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.7567 (2)	0.33711 (16)	0.19077 (15)	0.0503 (5)
C2	0.9239 (5)	0.3497 (6)	0.2123 (7)	0.083 (2)	0.720 (9)
H2A	0.9745	0.2880	0.1886	0.100*	0.720 (9)
H2B	0.9474	0.3571	0.2882	0.100*	0.720 (9)
C3	0.9802 (5)	0.4439 (3)	0.1552 (6)	0.0914 (16)	0.720 (9)
H3A	0.9587	0.4363	0.0790	0.110*	0.720 (9)
H3B	1.0881	0.4503	0.1690	0.110*	0.720 (9)
C4	0.9024 (6)	0.5410 (6)	0.1944 (10)	0.088 (2)	0.720 (9)
H4A	0.9390	0.5559	0.2671	0.105*	0.720 (9)
H4B	0.9256	0.5999	0.1505	0.105*	0.720 (9)
C2'	0.9248 (12)	0.3438 (17)	0.181 (2)	0.084 (4)	0.280 (9)
H2'1	0.9731	0.2830	0.2128	0.101*	0.280 (9)
H2'2	0.9448	0.3446	0.1058	0.101*	0.280 (9)
C3'	0.9899 (11)	0.4406 (8)	0.2338 (15)	0.086 (3)	0.280 (9)
H3'1	1.0962	0.4459	0.2230	0.103*	0.280 (9)
H3'2	0.9776	0.4382	0.3097	0.103*	0.280 (9)
C4'	0.9059 (10)	0.5334 (16)	0.184 (2)	0.079 (4)	0.280 (9)
H4'1	0.9408	0.5962	0.2205	0.094*	0.280 (9)
H4'2	0.9290	0.5394	0.1102	0.094*	0.280 (9)
C5	0.7371 (2)	0.52491 (16)	0.18965 (16)	0.0573 (5)
H5	0.6767	0.5838	0.1886	0.069*
C6	0.66896 (19)	0.43340 (13)	0.18680 (13)	0.0389 (4)
C7	0.49995 (19)	0.42239 (12)	0.17933 (13)	0.0373 (4)
C8	0.43427 (19)	0.37039 (13)	0.27260 (14)	0.0413 (4)
C9	0.4432 (2)	0.39694 (16)	0.37818 (16)	0.0556 (5)
H9	0.5006	0.4534	0.4027	0.067*
C10	0.3646 (3)	0.33750 (19)	0.44785 (18)	0.0682 (6)
H10	0.3679	0.3547	0.5197	0.082*
C11	0.2823 (3)	0.25373 (19)	0.41093 (19)	0.0698 (7)
H11	0.2312	0.2144	0.4588	0.084*
C12	0.2727 (2)	0.22584 (16)	0.30507 (18)	0.0594 (6)
H12	0.2171	0.1684	0.2809	0.071*
C13	0.3485 (2)	0.28613 (14)	0.23678 (15)	0.0445 (5)
C14	0.4437 (2)	0.34990 (13)	0.08747 (15)	0.0416 (4)
C15	0.2720 (3)	0.20116 (17)	0.05734 (19)	0.0673 (6)
H15A	0.2440	0.2333	−0.0108	0.081*
H15B	0.1802	0.1817	0.0894	0.081*
C16	0.3601 (4)	0.1063 (2)	0.0393 (3)	0.1041 (10)
H16A	0.3013	0.0596	−0.0060	0.156*
H16B	0.4501	0.1246	0.0060	0.156*
H16C	0.3862	0.0730	0.1062	0.156*
N1	0.35269 (17)	0.27687 (11)	0.12560 (13)	0.0478 (4)
O1	0.69642 (17)	0.25271 (11)	0.18388 (13)	0.0672 (4)
O2	0.42546 (14)	0.51902 (9)	0.16291 (10)	0.0500 (4)
H2	0.4545	0.5470	0.1095	0.075*
O3	0.46968 (16)	0.35971 (10)	−0.00586 (10)	0.0545 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0423 (12)	0.0531 (12)	0.0557 (12)	0.0060 (10)	0.0062 (9)	−0.0013 (9)
C2	0.042 (3)	0.092 (4)	0.114 (5)	0.018 (3)	−0.004 (2)	−0.020 (3)
C3	0.0365 (19)	0.119 (3)	0.120 (4)	−0.015 (2)	0.014 (2)	−0.021 (3)
C4	0.056 (4)	0.083 (4)	0.124 (5)	−0.019 (3)	0.006 (4)	−0.020 (4)
C2'	0.041 (6)	0.095 (7)	0.115 (10)	0.010 (6)	−0.002 (6)	−0.046 (7)
C3'	0.038 (4)	0.095 (6)	0.122 (7)	−0.001 (4)	−0.007 (5)	−0.026 (6)
C4'	0.040 (8)	0.090 (7)	0.105 (9)	−0.032 (7)	−0.001 (7)	−0.006 (8)
C5	0.0492 (13)	0.0518 (12)	0.0709 (14)	−0.0060 (10)	0.0031 (10)	−0.0075 (10)
C6	0.0371 (10)	0.0406 (10)	0.0397 (9)	0.0001 (8)	0.0069 (7)	−0.0012 (7)
C7	0.0355 (10)	0.0321 (9)	0.0453 (10)	0.0043 (7)	0.0089 (7)	0.0051 (7)
C8	0.0355 (10)	0.0419 (10)	0.0477 (11)	0.0061 (8)	0.0112 (8)	0.0071 (8)
C9	0.0560 (13)	0.0595 (12)	0.0525 (12)	0.0012 (10)	0.0129 (10)	0.0027 (9)
C10	0.0683 (16)	0.0865 (17)	0.0523 (12)	0.0039 (14)	0.0222 (11)	0.0136 (12)
C11	0.0559 (14)	0.0845 (17)	0.0720 (16)	−0.0013 (13)	0.0255 (12)	0.0310 (13)
C12	0.0425 (12)	0.0590 (13)	0.0779 (16)	−0.0075 (10)	0.0119 (10)	0.0185 (11)
C13	0.0311 (10)	0.0468 (11)	0.0563 (12)	0.0021 (8)	0.0080 (8)	0.0106 (9)
C14	0.0362 (10)	0.0399 (10)	0.0490 (11)	0.0050 (8)	0.0044 (8)	0.0067 (8)
C15	0.0561 (14)	0.0667 (14)	0.0781 (15)	−0.0177 (11)	−0.0031 (11)	−0.0031 (12)
C16	0.111 (2)	0.0780 (18)	0.120 (2)	−0.0010 (17)	−0.0182 (19)	−0.0309 (17)
N1	0.0410 (9)	0.0469 (9)	0.0556 (10)	−0.0095 (7)	0.0028 (7)	0.0026 (7)
O1	0.0585 (10)	0.0445 (8)	0.0994 (12)	0.0102 (7)	0.0112 (8)	0.0072 (7)
O2	0.0493 (8)	0.0395 (7)	0.0630 (9)	0.0117 (6)	0.0170 (6)	0.0098 (6)
O3	0.0646 (9)	0.0544 (8)	0.0447 (8)	−0.0034 (7)	0.0062 (7)	0.0047 (6)

Geometric parameters (Å, º) top

C1—O1	1.213 (2)	C7—O2	1.4190 (19)
C1—C6	1.465 (3)	C7—C8	1.505 (2)
C1—C2	1.507 (5)	C7—C14	1.544 (2)
C1—C2'	1.516 (10)	C8—C9	1.370 (3)
C2—C3	1.514 (7)	C8—C13	1.385 (3)
C2—H2A	0.9700	C9—C10	1.390 (3)
C2—H2B	0.9700	C9—H9	0.9300
C3—C4	1.528 (8)	C10—C11	1.368 (3)
C3—H3A	0.9700	C10—H10	0.9300
C3—H3B	0.9700	C11—C12	1.378 (3)
C4—C5	1.486 (6)	C11—H11	0.9300
C4—H4A	0.9700	C12—C13	1.371 (3)
C4—H4B	0.9700	C12—H12	0.9300
C2'—C3'	1.512 (10)	C13—N1	1.409 (2)
C2'—H2'1	0.9700	C14—O3	1.220 (2)
C2'—H2'2	0.9700	C14—N1	1.352 (2)
C3'—C4'	1.523 (10)	C15—N1	1.457 (3)
C3'—H3'1	0.9700	C15—C16	1.478 (3)
C3'—H3'2	0.9700	C15—H15A	0.9700
C4'—C5	1.516 (9)	C15—H15B	0.9700
C4'—H4'1	0.9700	C16—H16A	0.9600
C4'—H4'2	0.9700	C16—H16B	0.9600
C5—C6	1.325 (3)	C16—H16C	0.9600
C5—H5	0.9300	O2—H2	0.8200
C6—C7	1.511 (2)

O1—C1—C6	121.48 (17)	C5—C6—C7	122.64 (16)
O1—C1—C2	122.5 (4)	C1—C6—C7	116.83 (15)
C6—C1—C2	115.8 (3)	O2—C7—C8	107.48 (13)
O1—C1—C2'	118.8 (8)	O2—C7—C6	112.48 (13)
C6—C1—C2'	118.5 (9)	C8—C7—C6	115.65 (14)
C1—C2—C3	110.9 (5)	O2—C7—C14	107.18 (13)
C1—C2—H2A	109.5	C8—C7—C14	101.09 (14)
C3—C2—H2A	109.5	C6—C7—C14	112.06 (13)
C1—C2—H2B	109.5	C9—C8—C13	120.38 (17)
C3—C2—H2B	109.5	C9—C8—C7	130.30 (17)
H2A—C2—H2B	108.0	C13—C8—C7	109.25 (15)
C2—C3—C4	109.2 (7)	C8—C9—C10	118.5 (2)
C2—C3—H3A	109.8	C8—C9—H9	120.7
C4—C3—H3A	109.8	C10—C9—H9	120.7
C2—C3—H3B	109.8	C11—C10—C9	120.1 (2)
C4—C3—H3B	109.8	C11—C10—H10	119.9
H3A—C3—H3B	108.3	C9—C10—H10	119.9
C5—C4—C3	110.2 (5)	C10—C11—C12	122.05 (19)
C5—C4—H4A	109.6	C10—C11—H11	119.0
C3—C4—H4A	109.6	C12—C11—H11	119.0
C5—C4—H4B	109.6	C13—C12—C11	117.3 (2)
C3—C4—H4B	109.6	C13—C12—H12	121.3
H4A—C4—H4B	108.1	C11—C12—H12	121.3
C3'—C2'—C1	111.2 (10)	C12—C13—C8	121.61 (19)
C3'—C2'—H2'1	109.4	C12—C13—N1	128.59 (18)
C1—C2'—H2'1	109.4	C8—C13—N1	109.79 (15)
C3'—C2'—H2'2	109.4	O3—C14—N1	124.92 (17)
C1—C2'—H2'2	109.4	O3—C14—C7	125.90 (16)
H2'1—C2'—H2'2	108.0	N1—C14—C7	109.06 (15)
C2'—C3'—C4'	107.5 (19)	N1—C15—C16	113.4 (2)
C2'—C3'—H3'1	110.2	N1—C15—H15A	108.9
C4'—C3'—H3'1	110.2	C16—C15—H15A	108.9
C2'—C3'—H3'2	110.2	N1—C15—H15B	108.9
C4'—C3'—H3'2	110.2	C16—C15—H15B	108.9
H3'1—C3'—H3'2	108.5	H15A—C15—H15B	107.7
C5—C4'—C3'	112.7 (10)	C15—C16—H16A	109.5
C5—C4'—H4'1	109.0	C15—C16—H16B	109.5
C3'—C4'—H4'1	109.0	H16A—C16—H16B	109.5
C5—C4'—H4'2	109.0	C15—C16—H16C	109.5
C3'—C4'—H4'2	109.0	H16A—C16—H16C	109.5
H4'1—C4'—H4'2	107.8	H16B—C16—H16C	109.5
C6—C5—C4	125.3 (3)	C14—N1—C13	110.60 (15)
C6—C5—C4'	121.2 (8)	C14—N1—C15	122.69 (17)
C6—C5—H5	117.4	C13—N1—C15	126.72 (16)
C4—C5—H5	117.4	C7—O2—H2	109.5
C5—C6—C1	120.52 (17)

O1—C1—C2—C3	145.9 (5)	C6—C7—C8—C13	−124.16 (16)
C6—C1—C2—C3	−38.7 (7)	C14—C7—C8—C13	−2.91 (17)
C1—C2—C3—C4	60.3 (9)	C13—C8—C9—C10	0.0 (3)
C2—C3—C4—C5	−50.3 (10)	C7—C8—C9—C10	176.75 (18)
O1—C1—C2'—C3'	−156.7 (15)	C8—C9—C10—C11	0.9 (3)
C6—C1—C2'—C3'	36 (2)	C9—C10—C11—C12	−0.7 (4)
C1—C2'—C3'—C4'	−57 (3)	C10—C11—C12—C13	−0.5 (3)
C2'—C3'—C4'—C5	55 (3)	C11—C12—C13—C8	1.5 (3)
C3—C4—C5—C6	20.8 (10)	C11—C12—C13—N1	−177.50 (19)
C3'—C4'—C5—C6	−31 (3)	C9—C8—C13—C12	−1.2 (3)
C4—C5—C6—C1	1.4 (6)	C7—C8—C13—C12	−178.59 (16)
C4'—C5—C6—C1	7.2 (13)	C9—C8—C13—N1	177.89 (17)
C4—C5—C6—C7	−178.5 (6)	C7—C8—C13—N1	0.55 (19)
C4'—C5—C6—C7	−172.7 (13)	O2—C7—C14—O3	68.3 (2)
O1—C1—C6—C5	−176.95 (19)	C8—C7—C14—O3	−179.34 (17)
C2—C1—C6—C5	7.6 (4)	C6—C7—C14—O3	−55.6 (2)
C2'—C1—C6—C5	−9.6 (11)	O2—C7—C14—N1	−107.96 (15)
O1—C1—C6—C7	3.0 (3)	C8—C7—C14—N1	4.44 (17)
C2—C1—C6—C7	−172.5 (4)	C6—C7—C14—N1	128.19 (15)
C2'—C1—C6—C7	170.4 (10)	O3—C14—N1—C13	179.29 (17)
C5—C6—C7—O2	7.2 (2)	C7—C14—N1—C13	−4.45 (19)
C1—C6—C7—O2	−172.80 (14)	O3—C14—N1—C15	−1.0 (3)
C5—C6—C7—C8	−116.86 (19)	C7—C14—N1—C15	175.25 (16)
C1—C6—C7—C8	63.2 (2)	C12—C13—N1—C14	−178.41 (18)
C5—C6—C7—C14	127.99 (18)	C8—C13—N1—C14	2.5 (2)
C1—C6—C7—C14	−52.0 (2)	C12—C13—N1—C15	1.9 (3)
O2—C7—C8—C9	−67.7 (2)	C8—C13—N1—C15	−177.15 (18)
C6—C7—C8—C9	58.8 (2)	C16—C15—N1—C14	87.6 (3)
C14—C7—C8—C9	−179.91 (19)	C16—C15—N1—C13	−92.8 (3)
O2—C7—C8—C13	109.26 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3ⁱ	0.82	1.93	2.7350 (18)	167
C11—H11···O3ⁱⁱ	0.93	2.59	3.378 (3)	143
C12—H12···O2ⁱⁱⁱ	0.93	2.44	3.237 (2)	144

Symmetry codes: (i) −x+1, −y+1, −z; (ii) x−1/2, −y+1/2, z+1/2; (iii) −x+1/2, y−1/2, −z+1/2.

5-Bromo-3-hydroxy-1-methyl-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one (III_shelx) top

Crystal data top

C₁₅H₁₄BrNO₃	D_x = 1.580 Mg m⁻³
M_r = 336.18	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna2₁	Cell parameters from 2203 reflections
a = 7.8960 (3) Å	θ = 3.3–25.0°
b = 19.6458 (8) Å	µ = 2.92 mm⁻¹
c = 9.1088 (3) Å	T = 296 K
V = 1412.99 (9) Å³	Block, colourless
Z = 4	0.20 × 0.20 × 0.15 mm
F(000) = 680

Data collection top

Bruker Kappa APEXII CCD diffractometer	2203 reflections with I > 2σ(I)
ω and φ scan	R_int = 0.035
Absorption correction: multi-scan (SADABS; Bruker, 2008)	θ_max = 25.0°, θ_min = 3.3°
T_min = 0.550, T_max = 0.746	h = −9→9
25065 measured reflections	k = −23→23
2365 independent reflections	l = −10→10

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.033	w = 1/[σ²(F_o²) + (0.0653P)² + 0.434P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.101	(Δ/σ)_max < 0.001
S = 1.13	Δρ_max = 0.31 e Å⁻³
2365 reflections	Δρ_min = −0.78 e Å⁻³
182 parameters	Absolute structure: Flack x determined using 952 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.027 (4)
Primary atom site location: structure-invariant direct methods

Special details top

Refinement. IS3

Alert level C

1. PLAT918_ALERT_3_C Reflection(s) with I(obs) much Smaller I(calc) . 1 Check

This low-angle reflection is affected by the beam stop. Hence its I(obs) is much smaller than I(calc)

2. PLAT934_ALERT_3_C Number of (Iobs-Icalc)/Sigma(W) > 10 Outliers .. 1 Check

This low angle reflection is affected by the beam stop. Hence its I(obs) is much smaller than I(calc)

Alert level G

3. PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ············.. 1 Report

The hydroxy H atom was fixed at the calculated position and refined using a riding model with respect to its parent atom, with U_iso(H) = 1.5U_eq(O)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Br1	0.31672 (8)	0.32391 (3)	0.11497 (10)	0.0624 (3)
O1	0.2107 (6)	0.3645 (2)	0.7638 (7)	0.0660 (13)
O3	0.6023 (4)	0.43342 (18)	0.8846 (4)	0.0376 (7)
O2	0.5834 (3)	0.49520 (14)	0.5940 (4)	0.0314 (7)
H2	0.549453	0.511227	0.516215	0.047*
N1	0.6094 (5)	0.3447 (2)	0.7237 (5)	0.0364 (9)
C3	0.0437 (9)	0.5236 (5)	0.8846 (10)	0.083 (3)
H3A	0.111623	0.520576	0.973126	0.100*
H3B	−0.066127	0.541767	0.911606	0.100*
C4	0.1279 (8)	0.5717 (4)	0.7790 (8)	0.0615 (18)
H4A	0.046656	0.585447	0.704834	0.074*
H4B	0.163772	0.612134	0.831452	0.074*
C5	0.2784 (6)	0.5400 (3)	0.7055 (6)	0.0365 (11)
H5	0.357328	0.568568	0.661499	0.044*
C6	0.3050 (5)	0.4732 (2)	0.6997 (5)	0.0256 (9)
C7	0.4709 (5)	0.44369 (18)	0.6413 (4)	0.0231 (9)
C8	0.4589 (5)	0.3868 (2)	0.5291 (5)	0.0278 (9)
C9	0.3891 (6)	0.3861 (2)	0.3893 (5)	0.0316 (9)
H9	0.331908	0.423582	0.351670	0.038*
C10	0.4086 (7)	0.3264 (3)	0.3078 (6)	0.0397 (12)
C11	0.4935 (8)	0.2698 (3)	0.3627 (7)	0.0498 (14)
H11	0.503246	0.230694	0.305729	0.060*
C2	0.0215 (9)	0.4557 (5)	0.8241 (10)	0.079 (2)
H2A	−0.063138	0.457560	0.747037	0.095*
H2B	−0.020963	0.425903	0.900592	0.095*
C1	0.1816 (6)	0.4257 (3)	0.7623 (7)	0.0423 (12)
C14	0.5661 (5)	0.4075 (2)	0.7672 (5)	0.0291 (9)
C13	0.5457 (6)	0.3304 (2)	0.5830 (6)	0.0340 (12)
C12	0.5632 (7)	0.2715 (2)	0.5013 (7)	0.0460 (13)
H12	0.620511	0.233994	0.538961	0.055*
C15	0.7016 (8)	0.2968 (3)	0.8157 (9)	0.0565 (16)
H15A	0.741654	0.319712	0.902075	0.085*
H15B	0.796180	0.278850	0.762007	0.085*
H15C	0.627731	0.260216	0.843754	0.085*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0783 (4)	0.0760 (4)	0.0329 (4)	−0.0279 (3)	0.0028 (3)	−0.0196 (3)
O1	0.069 (3)	0.047 (2)	0.081 (4)	−0.0148 (19)	0.030 (2)	0.005 (2)
O3	0.0407 (17)	0.0458 (18)	0.0261 (18)	0.0064 (15)	−0.0042 (14)	−0.0053 (15)
O2	0.0303 (13)	0.0297 (13)	0.034 (2)	−0.0053 (11)	0.0053 (14)	0.0026 (14)
N1	0.044 (2)	0.0304 (18)	0.035 (2)	0.0091 (18)	−0.0023 (19)	0.0006 (19)
C3	0.059 (4)	0.127 (7)	0.063 (5)	0.037 (4)	0.020 (4)	−0.015 (5)
C4	0.053 (3)	0.072 (4)	0.060 (4)	0.034 (3)	−0.002 (3)	−0.019 (3)
C5	0.037 (2)	0.037 (2)	0.035 (3)	0.0113 (19)	0.000 (2)	−0.003 (2)
C6	0.0235 (18)	0.030 (2)	0.023 (2)	0.0021 (15)	0.0022 (15)	−0.0045 (18)
C7	0.0256 (17)	0.0225 (17)	0.021 (2)	0.0011 (14)	0.0039 (15)	−0.0038 (15)
C8	0.030 (2)	0.028 (2)	0.024 (2)	−0.0008 (16)	0.0084 (17)	−0.0049 (18)
C9	0.032 (2)	0.035 (2)	0.028 (2)	−0.0068 (18)	0.0033 (18)	−0.0074 (19)
C10	0.046 (3)	0.041 (3)	0.032 (3)	−0.016 (2)	0.007 (2)	−0.013 (2)
C11	0.056 (3)	0.037 (3)	0.057 (4)	−0.006 (2)	0.011 (3)	−0.025 (2)
C2	0.045 (3)	0.120 (7)	0.072 (5)	0.000 (4)	0.026 (3)	0.008 (5)
C1	0.033 (2)	0.053 (3)	0.041 (3)	−0.007 (2)	0.005 (2)	0.000 (3)
C14	0.0254 (19)	0.032 (2)	0.030 (2)	0.0037 (16)	0.0052 (17)	−0.0012 (18)
C13	0.040 (2)	0.026 (2)	0.036 (4)	0.0070 (16)	0.004 (2)	−0.0038 (17)
C12	0.057 (3)	0.026 (2)	0.055 (4)	0.009 (2)	0.005 (3)	−0.011 (2)
C15	0.069 (4)	0.039 (3)	0.061 (4)	0.019 (3)	−0.017 (3)	0.008 (3)

Geometric parameters (Å, º) top

Br1—C10	1.902 (6)	C6—C7	1.528 (5)
O1—C1	1.226 (8)	C7—C8	1.518 (5)
O3—C14	1.219 (6)	C7—C14	1.544 (6)
O2—C7	1.414 (5)	C8—C9	1.388 (7)
O2—H2	0.8200	C8—C13	1.392 (6)
N1—C14	1.340 (6)	C9—C10	1.395 (7)
N1—C13	1.406 (7)	C9—H9	0.9300
N1—C15	1.456 (7)	C10—C11	1.392 (9)
C3—C2	1.453 (12)	C11—C12	1.377 (9)
C3—C4	1.503 (12)	C11—H11	0.9300
C3—H3A	0.9700	C2—C1	1.504 (9)
C3—H3B	0.9700	C2—H2A	0.9700
C4—C5	1.499 (7)	C2—H2B	0.9700
C4—H4A	0.9700	C13—C12	1.382 (7)
C4—H4B	0.9700	C12—H12	0.9300
C5—C6	1.330 (7)	C15—H15A	0.9600
C5—H5	0.9300	C15—H15B	0.9600
C6—C1	1.464 (7)	C15—H15C	0.9600

C7—O2—H2	109.5	C8—C9—H9	121.5
C14—N1—C13	111.3 (4)	C10—C9—H9	121.5
C14—N1—C15	123.6 (5)	C11—C10—C9	122.2 (5)
C13—N1—C15	125.1 (5)	C11—C10—Br1	119.6 (4)
C2—C3—C4	112.8 (6)	C9—C10—Br1	118.1 (4)
C2—C3—H3A	109.0	C12—C11—C10	120.1 (4)
C4—C3—H3A	109.0	C12—C11—H11	119.9
C2—C3—H3B	109.0	C10—C11—H11	119.9
C4—C3—H3B	109.0	C3—C2—C1	113.6 (6)
H3A—C3—H3B	107.8	C3—C2—H2A	108.9
C5—C4—C3	112.0 (5)	C1—C2—H2A	108.9
C5—C4—H4A	109.2	C3—C2—H2B	108.9
C3—C4—H4A	109.2	C1—C2—H2B	108.9
C5—C4—H4B	109.2	H2A—C2—H2B	107.7
C3—C4—H4B	109.2	O1—C1—C6	120.4 (5)
H4A—C4—H4B	107.9	O1—C1—C2	122.5 (6)
C6—C5—C4	123.6 (5)	C6—C1—C2	117.1 (5)
C6—C5—H5	118.2	O3—C14—N1	125.7 (4)
C4—C5—H5	118.2	O3—C14—C7	125.0 (4)
C5—C6—C1	120.5 (4)	N1—C14—C7	109.2 (4)
C5—C6—C7	121.6 (4)	C12—C13—C8	121.7 (5)
C1—C6—C7	117.7 (4)	C12—C13—N1	128.5 (4)
O2—C7—C8	111.2 (3)	C8—C13—N1	109.7 (4)
O2—C7—C6	111.9 (3)	C11—C12—C13	118.3 (5)
C8—C7—C6	117.4 (3)	C11—C12—H12	120.9
O2—C7—C14	104.5 (3)	C13—C12—H12	120.9
C8—C7—C14	101.0 (3)	N1—C15—H15A	109.5
C6—C7—C14	109.5 (3)	N1—C15—H15B	109.5
C9—C8—C13	120.7 (4)	H15A—C15—H15B	109.5
C9—C8—C7	130.5 (4)	N1—C15—H15C	109.5
C13—C8—C7	108.6 (4)	H15A—C15—H15C	109.5
C8—C9—C10	116.9 (5)	H15B—C15—H15C	109.5

C2—C3—C4—C5	−45.4 (9)	C5—C6—C1—C2	3.5 (8)
C3—C4—C5—C6	18.6 (9)	C7—C6—C1—C2	177.9 (6)
C4—C5—C6—C1	2.3 (8)	C3—C2—C1—O1	148.5 (8)
C4—C5—C6—C7	−171.9 (5)	C3—C2—C1—C6	−31.0 (10)
C5—C6—C7—O2	−1.3 (6)	C13—N1—C14—O3	179.3 (4)
C1—C6—C7—O2	−175.7 (4)	C15—N1—C14—O3	2.8 (8)
C5—C6—C7—C8	−131.6 (5)	C13—N1—C14—C7	−3.8 (5)
C1—C6—C7—C8	54.0 (6)	C15—N1—C14—C7	179.7 (5)
C5—C6—C7—C14	114.1 (5)	O2—C7—C14—O3	66.0 (5)
C1—C6—C7—C14	−60.3 (5)	C8—C7—C14—O3	−178.5 (4)
O2—C7—C8—C9	−68.7 (5)	C6—C7—C14—O3	−54.0 (5)
C6—C7—C8—C9	62.0 (6)	O2—C7—C14—N1	−110.9 (4)
C14—C7—C8—C9	−179.1 (4)	C8—C7—C14—N1	4.6 (4)
O2—C7—C8—C13	106.6 (4)	C6—C7—C14—N1	129.1 (4)
C6—C7—C8—C13	−122.7 (4)	C9—C8—C13—C12	−1.1 (7)
C14—C7—C8—C13	−3.8 (4)	C7—C8—C13—C12	−177.0 (4)
C13—C8—C9—C10	0.7 (6)	C9—C8—C13—N1	177.7 (4)
C7—C8—C9—C10	175.5 (4)	C7—C8—C13—N1	1.9 (5)
C8—C9—C10—C11	0.1 (7)	C14—N1—C13—C12	−180.0 (5)
C8—C9—C10—Br1	−179.3 (3)	C15—N1—C13—C12	−3.5 (8)
C9—C10—C11—C12	−0.6 (8)	C14—N1—C13—C8	1.3 (5)
Br1—C10—C11—C12	178.9 (4)	C15—N1—C13—C8	177.7 (5)
C4—C3—C2—C1	52.1 (10)	C10—C11—C12—C13	0.2 (8)
C5—C6—C1—O1	−176.1 (6)	C8—C13—C12—C11	0.6 (8)
C7—C6—C1—O1	−1.6 (8)	N1—C13—C12—C11	−178.0 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···O3ⁱ	0.93	2.54	3.115 (7)	120
O2—H2···O3ⁱ	0.82	2.01	2.785 (5)	156

Symmetry code: (i) −x+1, −y+1, z−1/2.

Experimental (X-ray crystallography) and optimized (PM7) bond lengths (Å) involving the non-H atoms of IS1 top

Parameters	Optimized	Experimental
C17—C16	1.240	1.217 (5)
O1—C1	1.218	1.220 (2)
O3—C14	1.231	1.221 (3)
O2—C7	1.394	1.420 (2)
N1—C14	1.344	1.350 (3)
N1—C13	1.383	1.410 (3)
N1—C15	1.421	1.456 (3)
C8—C7	1.506	1.510 (3)
C8—C13	1.349	1.392 (3)
C8—C9	1.378	1.371 (3)
C7—C6	1.516	1.517 (3)
C7—C14	1.520	1.553 (3)
C1—C6	1.446	1.476 (3)
C6—C5	1.337	1.332 (3)
C13—C12	1.375	1.378 (3)
C5—C4	1.471	1.495 (3)
C2—C3	1.482	1.512 (3)
C3—C4	1.468	1.506 (3)
C9—C10	1.372	1.397 (3)
C11—C12	1.367	1.387 (4)
C11—C10	1.357	1.370 (4)
C15—C16	1.359	1.467 (4)

Experimental (X-ray crystallography) and optimized (PM7) bond lengths (Å) involving the non-H atoms of IS2 top

Parameters	Optimized	Experimental
C1—O1	1.229	1.213 (2)
C1—C2	1.515	1.507 (5)
C1—C6	1.499	1.465 (3)
C2—C3	1.518	1.514 (7)
C3—C4	1.521	1.528 (8)
C4—C5	1.499	1.486 (6)
C5—C6	1.351	1.325 (3)
C6—C7	1.511	1.511 (2)
C7—C8	1.506	1.505 (2)
C7—C14	1.567	1.544 (2)
C7—O2	1.437	1.4190 (19)
C8—C9	1.388	1.370 (3)
C8—C13	1.401	1.385 (3)
C9—C10	1.395	1.390 (3)
C10—C11	1.405	1.368 (3)
C11—C12	1.399	1.378 (3)
C12—C13	1.383	1.371 (3)
C13—N1	1.403	1.409 (2)
C14—N1	1.400	1.352 (2)
C14—O3	1.226	1.220 (2)
C15—C16	1.519	1.478 (3)
C15—N1	1.443	1.457 (3)

Experimental (X-ray crystallography) and optimized (PM7) bond lengths (Å) involving the non-H atoms of IS3 (Å) top

Parameters	Optimized	Experimental
Br1—C10	1.893	1.902 (6)
O1—C1	1.228	1.226 (8)
O3—C14	1.231	1.219 (6)
O2—C7	1.434	1.414 (5)
N1—C14	1.392	1.340 (6)
N1—C13	1.395	1.406 (7)
N1—C15	1.434	1.456 (7)
C3—C4	1.521	1.503 (12)
C3—C2	1.515	1.453 (12)
C4—C5	1.490	1.499 (7)
C5—C6	1.349	1.330 (7)
C6—C7	1.505	1.528 (5)
C6—C1	1.494	1.464 (7)
C7—C8	1.510	1.518 (5)
C7—C14	1.550	1.544 (6)
C8—C9	1.388	1.388 (7)
C8—C13	1.403	1.392 (6)
C9—C10	1.399	1.395 (7)
C10—C11	1.405	1.392 (9)
C2—C1	1.513	1.504 (9)
C11—C12	1.382	1.377 (9)
C13—C12	1.381	1.382 (7)

Experimental (X-ray crystallography) and optimized (PM7) bond angles (°) involving the non-H atoms of IS1 top

Parameters	Optimized	Experimental
O2—C7—C6	114.98	111.89 (16)
O2—C7—C14	109.32	107.55 (15)
O1—C1—C6	120.84	120.88 (19)
O3—C14—N1	124.02	126.47 (19)
C14—N1—C15	125.01	124.0 (2)
N1—C13—C12	128.41	128.1 (2)
C7—C8—C13	110.24	109.08 (18)
C8—C7—C6	113.58	114.55 (16)
C8—C7—C14	98.94	101.10 (16)
C13—C8—C9	119.77	119.8 (2)
C12—C11—C10	120.42	121.5 (2)
O2—C7—C8	106.07	108.55 (16)
O1—C1—C2	120.67	121.29 (19)
O3—C14—C7	125.14	124.63 (18)
C8—C13—C12	121.03	122.2 (2)
C9—C10—C11	120.33	120.8 (2)

Experimental (X-ray crystallography) and optimized (PM7) bond angles (°) involving the non-H atoms of IS2 top

Parameters	Optimized	Experimental
C6—C1—O1	121.10	121.48 (17)
C7—C8—C13	109.68	109.25 (15)
C7—C14—O3	125.22	125.90 (16)
C8—C9—C10	118.21	118.5 (2)
C8—C13—C12	121.20	121.61 (19)
C9—C10—C11	120.62	120.1 (2)
C11—C12—C13	118.04	117.3 (2)
C12—C13—N1	128.74	128.59 (18)
C13—N1—C14	111.04	110.60 (15)
C13—N1—C15	125.44	126.72 (16)
C16—C15—N1	112.50	113.4 (2)
C14—N1—C15	123.51	122.69 (17)
N1—C14—O3	127.35	124.92 (17)

Experimental (X-ray crystallography) and optimized (PM7) bond angles (°) involving the non-H atoms of IS3 top

Parameters	Optimized	Experimental
O1—C1—C6	120.97	120.4 (5)
Br1—C10—C9	121.81	118.1 (4)
O3—C14—C7	127.76	125.0 (4)
O2—C7—C6	112	111.9 (3)
N1—C13—C12	128.48	128.5 (4)
C7—C8—C9	132.04	130.5 (4)
C8—C7—C14	103.09	101.0 (3)
C8—C9—C10	121.49	116.9 (5)
C8—C13—C12	120.89	121.7 (5)
C9—C10—C11	117.34	122.2 (5)
C10—C11—C12	121.62	120.1 (4)
N1—C14—C7	105.49	109.2 (4)
C11—C12—C13	119.35	118.3 (5)
Br1—C10—C11	119.05	119.6 (4)
O3—C14—N1	126.55	125.7 (4)

Mulliken atomic charges of IS1 top

No	Atom	Charge	No	Atom	Charge
1	C17	-0.3745	12	C11	-0.1224
2	O2	-0.5446	13	C4	-0.3959
3	O1	-0.4810	14	C12	-0.2986
4	O3	-0.4976	15	C10	-0.2727
5	N1	-0.6113	16	C15	-0.1100
6	C8	-0.1583	17	C16	-0.2432
7	C6	-0.2569	18	C1	0.5185
8	C5	-0.0593	19	C14	0.6083
9	C2	-0.4697	20	C13	0.2769
10	C3	-0.3351	21	C7	0.2383
11	C9	-0.0997

Mulliken atomic charges of IS2 top

No	Atom	Charge	No	Atom	Charge
1	C2	-0.4717	11	C15	-0.0829
2	C3	-0.3333	12	C16	-0.6165
3	C4	-0.3952	13	N1	-0.6074
4	C5	-0.0600	14	O1	-0.4818
5	C6	-0.2601	15	O2	-0.5427
6	C8	-0.1619	16	O3	-0.4887
7	C9	-0.1000	17	C1	0.5162
8	C10	-0.2737	18	C7	0.2314
9	C11	-0.1223	19	C13	0.2721
10	C12	-0.3013	20	C14	0.6103

Mulliken atomic charges of IS3 top

No	Atom	Charge	No	Atom	Charge
1	C2	-0.4712	12	C16	-0.6165
2	C3	-0.3334	13	N1	-0.6063
3	C4	-0.4010	14	O1	-0.4820
4	C5	-0.0307	15	O2	-0.5471
5	C6	-0.2515	16	O3	-0.4462
6	C8	-0.2184	17	C1	0.5151
7	C9	-0.1340	18	C7	0.2608
8	C10	-0.5168	19	C13	0.2896
9	C11	-0.1509	20	C14	0.5952
10	C12	-0.2977	21	Br	0.4344
11	C15	-0.3149

Quantum chemical parameters of IS1, IS2 and IS3 top

Parameters	Units	IS1	IS2	IS3
E_HOMO	eV	-8.661	-8.584	-8.706
E_LUMO	eV	-0.355	-0.324	-0.463
Energy gap (E_LUMO – E_HOMO)	eV	8.306	8.260	8.243
Electronic energy	eV	-25238.3454	-24210.9893	-23758.9724
Chemical potential (µ)	eV	-4.508	-4.454	-4.585
Global hardness (η)	eV	4.153	4.130	4.121
Global softness (S)	eV^-1	0.1118	0.121	0.121
Electrophilicity index (ω)	eV	2.252	2.402	2.550
Electronegativity (χ)	eV	4.508	4.454	4.584
Dipole (µ)	Debye	4.303	3.771	1.450
Static second-order hyperpolarizability (γ)	10–35 esu	1.8889	0.9213	1.2904

Druglikeness of IS1, IS2 and IS3 top

Compounds	log P	TPSA	MW	Volume	nON	nOH-NH	nrotb	No. violations
IS1	1.99	57.61	283.33	259.99	4	1	3	0
IS2	1.72	57.61	271.32	248.82	4	1	2	0
IS3	2.13	57.61	336.19	249.90	1	1	1	0

Bioactive scores for IS1, IS2 and IS3. The column headings are defined as: G protein-coupled receptors (GPCR) ligand activity, ion channel modulation (ICM), kinase inhibition activity (KI), nuclear receptor ligand activity (NR), protease inhibitor (PI) and enzyme inhibitor (EI). top

Compounds	GPCR	ICM	KI	NR	PI	EI
IS1	-0.29	-0.52	-1.04	-0.22	-0.59	-0.31
IS2	-0.29	-0.60	-1.02	-0.24	-0.63	-0.30
IS3	-0.46	-0.64	-1.05	-0.40	-0.69	-0.33

Diameter of the inhibition zone (mm) of compounds IS1, IS2 and IS3 towards Eschericia coli, Proteus Vulgaris, Shigella flexneri, staphylococcus aureus and Micrococcus luteus. top

Compounds	E. coli	P. vulgaris	S. flexneri	S. aureus	M. luteus
IS1	10	10	10	12	13
IS2	13	11	12	13	14
IS3	14	13	14	15	15

Diameter of the inhibition zone (mm) of compounds IS1, IS2 and IS3 towards Aspergillus niger top

Compound	Aspergillus niger	Compound	Aspergillus niger
IS1	16	IS3	18
IS2	17

Molecular docking interactions of IS1, IS2 and IS3 against PBP2a top

Inhibitor	Binding energy (K cal mol^-1)	Distance (Å)	Inhibition constant (µM)	Binding site of protein	Binding site of ligand
IS1	-6.11	2.94,2.84	33.27	OH (Thr600), COOH (Glu447)	Aliphatic CHC═O
IS2	-7.37	2.43,2.79,2.69,2.85	3.95	COOH (Glu447), COOH (Gln521), NH₂ (Gln521), NH₂(Gln521)	OH, C═O, C═O, α,β-unsaturated ketone
IS3	-7.23	2.86,3.24,2.89,3.09,3.35	14.69	NH₂ (Ser400), COOH (Thr399), COOH (Glu602), NH₂ (Lys604), NH₂ (Asn632)	OH, Ar-CH, N-CH₃, N-CH₃, Br

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Synthesis, spectroscopic investigation, crystal structure analysis, quantum chemical study, biological activity and mol­ecular docking of three isatin derivatives

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Synthesis, spectroscopic investigation, crystal structure analysis, quantum chemical study, biological activity and molecular docking of three isatin derivatives