Hirshfeld analysis and mol­ecular docking with the RDR enzyme of 2-(5-chloro-2-oxoindolin-3-yl­idene)-N-methyl­hydrazinecarbo­thio­amide

The title isatin thio­semicarbazone derivative is an inter­mediate in the synthetic pathway of HIV-1 reverse transcriptase inhibitors. A mol­ecular docking evaluation of the title compound with the ribonucleoside diphosphate reductase (RDR) enzyme was carried out.

Key indicators

• Single-crystal X-ray study
• T = 200 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.020
• wR factor = 0.056
• Data-to-parameter ratio = 14.0

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT927_ALERT_1_A Reported and Calculated  wR2 Differ by .........    -0.0695 Check

Alert level B
PLAT920_ALERT_1_B Theta(Max)  in CIF and FCF Differ by ...........      18.20 Degree
PLAT921_ALERT_1_B R1  in the CIF and FCF Differ by ...............    -0.0132 Check
PLAT922_ALERT_1_B wR2 in the CIF and FCF Differ by ...............    -0.0248 Check
PLAT925_ALERT_1_B The Reported and Calculated Rho(max) Differ by .       2.92 eA-3
PLAT926_ALERT_1_B Reported and Calculated   R1 Differ by .........    -0.0410 Check
PLAT928_ALERT_1_B Reported and Calculated    S value   Differ by .     -0.455
PLAT971_ALERT_2_B Check Calcd Residual Density  0.10A From      S1       3.11 eA-3
PLAT971_ALERT_2_B Check Calcd Residual Density  0.08A From     Cl1       2.58 eA-3

Alert level C
PLAT923_ALERT_1_C S    values in the CIF and FCF Differ by .......      0.080 Check

Alert level G
PLAT013_ALERT_1_G N.O.K. _shelx_hkl_checksum found in CIF ........     Please Check
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600        403 Note
PLAT953_ALERT_1_G Reported (CIF) and Actual (FCF) Hmax Differ by .          4 Units
PLAT954_ALERT_1_G Reported (CIF) and Actual (FCF) Kmax Differ by .          4 Units
PLAT955_ALERT_1_G Reported (CIF) and Actual (FCF) Lmax Differ by .         13 Units
PLAT956_ALERT_1_G Calculated (ThMax) and Actual (FCF) Hmax Differ           4 Units
PLAT957_ALERT_1_G Calculated (ThMax) and Actual (FCF) Kmax Differ           4 Units
PLAT958_ALERT_1_G Calculated (ThMax) and Actual (FCF) Lmax Differ          13 Units
PLAT978_ALERT_2_G Number C-C Bonds with Positive Residual Density.          5 Note
PLAT996_ALERT_1_G Non-Standard SHELXL LIST 4 Style FCF Supplied ..          ! Check

   1 ALERT level A = Most likely a serious problem - resolve or explain
   8 ALERT level B = A potentially serious problem, consider carefully
   1 ALERT level C = Check. Ensure it is not caused by an omission or oversight
  10 ALERT level G = General information/check it is not something unexpected

  16 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2008), DIAMOND (Brandenburg, 2006), GOLD (Chen, 2015), MOPAC (Stewart, 2013) and Crystal Explorer (Wolff et al., 2012); software used to prepare material for publication: SHELXL2016 (Sheldrick, 2015b), publCIF (Westrip, 2010) and enCIFer (Allen et al., 2004).

2-(5-Chloro-2-oxoindolin-3-ylidene)-N-methylhydrazinecarbothioamide

Crystal data

C10H9ClN4OS	Dx = 1.498 Mg m^−3
Mr = 268.72	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 9936 reflections
a = 6.2584 (1) Å	θ = 3.0–40.9°
b = 10.1734 (2) Å	µ = 0.48 mm^−1
c = 18.7183 (3) Å	T = 200 K
V = 1191.78 (4) Å^3	Prism, yellow
Z = 4	0.46 × 0.16 × 0.12 mm
F(000) = 552

Data collection

Bruker APEXII CCD area detector diffractometer	2295 reflections with I > 2σ(I)
Radiation source: fine-focus sealed X-ray tube, Bruker APEXII CCD	Rint = 0.013
φ and ω scans	θmax = 26.0°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2014)	h = −7→5
Tmin = 0.697, Tmax = 0.749	k = −12→12
10426 measured reflections	l = −23→23
2342 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.020	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.056	w = 1/[σ^2(Fo^2) + (0.0338P)^2 + 0.2804P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
2342 reflections	Δρmax = 0.19 e Å^−3
167 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Absolute structure: Flack x determined using 940 quotients [(I^+)-(I^-)]/[(I^+)+(I^-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.006 (9)

Special details

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.

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

	x	y	z	Uiso*/Ueq
C1	0.4431 (3)	0.63210 (18)	0.56919 (9)	0.0229 (4)
C2	0.3885 (3)	0.51360 (17)	0.61332 (9)	0.0200 (4)
C3	0.5539 (3)	0.41669 (18)	0.59914 (9)	0.0199 (4)
C4	0.5853 (3)	0.28884 (18)	0.62247 (9)	0.0215 (3)
H4	0.487362	0.247309	0.653982	0.026*
C5	0.7655 (3)	0.22425 (18)	0.59789 (9)	0.0246 (4)
C6	0.9124 (3)	0.2840 (2)	0.55278 (10)	0.0278 (4)
H6	1.036794	0.237337	0.538476	0.033*
C7	0.8793 (3)	0.4117 (2)	0.52828 (10)	0.0271 (4)
H7	0.977419	0.452902	0.496717	0.033*
C8	0.6980 (3)	0.47585 (18)	0.55173 (9)	0.0226 (4)
C9	−0.0829 (3)	0.58961 (18)	0.70690 (9)	0.0216 (4)
C10	−0.2880 (3)	0.4484 (2)	0.78682 (11)	0.0345 (4)
H10A	−0.260071	0.490692	0.832924	0.052*
H10B	−0.301350	0.353251	0.793692	0.052*
H10C	−0.421127	0.483020	0.766648	0.052*
Cl1	0.80561 (8)	0.06052 (5)	0.62274 (3)	0.03753 (15)
N1	0.6267 (3)	0.60279 (16)	0.53459 (8)	0.0254 (3)
H1N	0.684 (4)	0.652 (2)	0.5082 (14)	0.037 (7)*
N2	0.2289 (3)	0.49844 (14)	0.65623 (7)	0.0210 (3)
N3	0.0946 (3)	0.60072 (16)	0.66389 (8)	0.0236 (3)
H3N	0.110 (4)	0.669 (2)	0.6405 (12)	0.031 (6)*
N4	−0.1123 (3)	0.47545 (16)	0.73815 (8)	0.0244 (3)
H4N	−0.014 (4)	0.415 (3)	0.7332 (13)	0.040 (7)*
O1	0.3382 (2)	0.73458 (13)	0.56517 (7)	0.0295 (3)
S1	−0.24203 (8)	0.72186 (5)	0.71392 (3)	0.03074 (13)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0266 (9)	0.0228 (9)	0.0194 (8)	−0.0015 (7)	−0.0011 (7)	0.0016 (7)
C2	0.0213 (8)	0.0188 (8)	0.0198 (8)	0.0008 (7)	−0.0020 (6)	0.0005 (6)
C3	0.0189 (8)	0.0235 (9)	0.0174 (7)	−0.0005 (7)	−0.0008 (6)	−0.0016 (7)
C4	0.0212 (8)	0.0240 (9)	0.0194 (7)	0.0020 (7)	0.0004 (7)	0.0010 (7)
C5	0.0249 (9)	0.0249 (8)	0.0241 (8)	0.0059 (9)	−0.0053 (7)	−0.0014 (7)
C6	0.0201 (9)	0.0358 (10)	0.0275 (9)	0.0053 (8)	0.0005 (7)	−0.0074 (8)
C7	0.0221 (9)	0.0352 (10)	0.0240 (8)	−0.0047 (8)	0.0051 (7)	−0.0038 (8)
C8	0.0245 (10)	0.0248 (9)	0.0185 (7)	−0.0041 (7)	−0.0002 (7)	−0.0022 (6)
C9	0.0178 (8)	0.0240 (9)	0.0231 (8)	0.0004 (7)	−0.0022 (7)	−0.0042 (7)
C10	0.0261 (10)	0.0391 (11)	0.0382 (10)	−0.0029 (9)	0.0065 (9)	0.0058 (9)
Cl1	0.0386 (3)	0.0307 (3)	0.0433 (3)	0.0154 (2)	−0.0012 (2)	0.0053 (2)
N1	0.0305 (9)	0.0239 (8)	0.0219 (7)	−0.0032 (7)	0.0054 (6)	0.0032 (6)
N2	0.0202 (8)	0.0197 (6)	0.0230 (7)	0.0018 (6)	−0.0012 (6)	−0.0014 (5)
N3	0.0239 (8)	0.0193 (7)	0.0277 (8)	0.0042 (6)	0.0044 (6)	0.0017 (6)
N4	0.0192 (8)	0.0246 (8)	0.0294 (8)	0.0016 (7)	0.0017 (6)	0.0008 (6)
O1	0.0366 (8)	0.0230 (7)	0.0289 (6)	0.0061 (6)	−0.0009 (6)	0.0066 (5)
S1	0.0266 (2)	0.0249 (2)	0.0407 (3)	0.0070 (2)	0.0042 (2)	−0.00341 (19)

Geometric parameters (Å, º)

C1—O1	1.234 (2)	C7—H7	0.9500
C1—N1	1.352 (3)	C8—N1	1.404 (2)
C1—C2	1.501 (2)	C9—N4	1.313 (2)
C2—N2	1.291 (2)	C9—N3	1.376 (2)
C2—C3	1.454 (2)	C9—S1	1.6792 (18)
C3—C4	1.386 (3)	C10—N4	1.455 (2)
C3—C8	1.401 (3)	C10—H10A	0.9800
C4—C5	1.384 (3)	C10—H10B	0.9800
C4—H4	0.9500	C10—H10C	0.9800
C5—C6	1.388 (3)	N1—H1N	0.79 (3)
C5—Cl1	1.7475 (19)	N2—N3	1.345 (2)
C6—C7	1.393 (3)	N3—H3N	0.83 (3)
C6—H6	0.9500	N4—H4N	0.87 (3)
C7—C8	1.381 (3)
O1—C1—N1	127.53 (18)	C7—C8—N1	128.59 (18)
O1—C1—C2	126.21 (17)	C3—C8—N1	109.59 (16)
N1—C1—C2	106.26 (16)	N4—C9—N3	116.50 (16)
N2—C2—C3	125.68 (16)	N4—C9—S1	126.19 (14)
N2—C2—C1	127.93 (16)	N3—C9—S1	117.30 (13)
C3—C2—C1	106.39 (15)	N4—C10—H10A	109.5
C4—C3—C8	120.74 (17)	N4—C10—H10B	109.5
C4—C3—C2	132.84 (17)	H10A—C10—H10B	109.5
C8—C3—C2	106.41 (16)	N4—C10—H10C	109.5
C5—C4—C3	117.17 (17)	H10A—C10—H10C	109.5
C5—C4—H4	121.4	H10B—C10—H10C	109.5
C3—C4—H4	121.4	C1—N1—C8	111.32 (16)
C4—C5—C6	122.28 (18)	C1—N1—H1N	123.1 (19)
C4—C5—Cl1	118.75 (15)	C8—N1—H1N	125.5 (19)
C6—C5—Cl1	118.95 (15)	C2—N2—N3	117.21 (15)
C5—C6—C7	120.64 (18)	N2—N3—C9	120.21 (15)
C5—C6—H6	119.7	N2—N3—H3N	121.4 (17)
C7—C6—H6	119.7	C9—N3—H3N	118.2 (17)
C8—C7—C6	117.32 (17)	C9—N4—C10	123.53 (17)
C8—C7—H7	121.3	C9—N4—H4N	118.4 (17)
C6—C7—H7	121.3	C10—N4—H4N	117.8 (17)
C7—C8—C3	121.81 (18)
O1—C1—C2—N2	−2.4 (3)	C6—C7—C8—N1	−179.15 (17)
N1—C1—C2—N2	178.37 (18)	C4—C3—C8—C7	−2.1 (3)
O1—C1—C2—C3	178.15 (18)	C2—C3—C8—C7	178.33 (16)
N1—C1—C2—C3	−1.04 (19)	C4—C3—C8—N1	177.97 (16)
N2—C2—C3—C4	2.7 (3)	C2—C3—C8—N1	−1.55 (19)
C1—C2—C3—C4	−177.88 (19)	O1—C1—N1—C8	−179.07 (18)
N2—C2—C3—C8	−177.86 (17)	C2—C1—N1—C8	0.1 (2)
C1—C2—C3—C8	1.57 (19)	C7—C8—N1—C1	−178.94 (18)
C8—C3—C4—C5	1.1 (2)	C3—C8—N1—C1	0.9 (2)
C2—C3—C4—C5	−179.57 (18)	C3—C2—N2—N3	178.33 (16)
C3—C4—C5—C6	1.1 (3)	C1—C2—N2—N3	−1.0 (3)
C3—C4—C5—Cl1	−177.22 (13)	C2—N2—N3—C9	177.74 (16)
C4—C5—C6—C7	−2.3 (3)	N4—C9—N3—N2	−0.8 (2)
Cl1—C5—C6—C7	176.06 (14)	S1—C9—N3—N2	179.76 (13)
C5—C6—C7—C8	1.2 (3)	N3—C9—N4—C10	178.17 (17)
C6—C7—C8—C3	1.0 (3)	S1—C9—N4—C10	−2.4 (3)

Hydrogen-bond geometry (Å, º)

Cg is the centroid of the C3–C8 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3N···O1	0.83 (2)	2.12 (3)	2.756 (2)	134 (2)
N1—H1N···O1^i	0.79 (2)	2.04 (3)	2.824 (2)	175 (2)
N4—H4N···S1^ii	0.88 (3)	2.72 (3)	3.518 (2)	152 (2)
C6—H6···Cg^iii	0.95	2.61	3.410 (2)	142

Symmetry codes: (i) x+1/2, −y+3/2, −z+1; (ii) −x, y−1/2, −z+3/2; (iii) x+1/2, −y+1/2, −z+1.