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N-[(4-Fluoro­phen­yl)sulfan­yl]phthalimide (C14H8FNO2S, FP) was synthesized and characterized using X-ray crystallography. It was then investigated via quantum chemical analysis using the density functional theory (DFT) approach, as well as spectrochemically using FT–IR and 1H and 13C NMR spectroscopy, and elemental analysis. The observed and stimulated spectra are in very good agreement for the DFT method. The in vitro anti­microbial activity of FP against three Gram-positive bacteria, three Gram-negative bacteria and two fungi were determined using the serial dilution method, and FP showed the highest anti­bacterial activity against E. coli, with a MIC of 128 µg ml−1. Druglikeness, ADME (absorption, distribution, metabolism and excretion) and toxicology studies were carried out to theoretically examine the drug properties of FP.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229623003418/zo3030sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229623003418/zo3030Isup2.hkl
Contains datablock I

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S2053229623003418/zo3030sup3.pdf
Additional figures and tables

cml

Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229623003418/zo3030Isup4.cml
Supplementary material

CCDC reference: 2215029

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: SHELXTL (Bruker, 2006) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXTL (Bruker, 2006).

2-[(4-Fluorophenyl)sulfanyl]isoindole-1,3-dione top
Crystal data top
C14H8FNO2SZ = 2
Mr = 273.27F(000) = 280
Triclinic, P1Dx = 1.491 Mg m3
a = 7.5224 (18) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.4415 (18) ÅCell parameters from 9583 reflections
c = 10.820 (3) Åθ = 3.1–28.2°
α = 91.437 (9)°µ = 0.27 mm1
β = 104.157 (10)°T = 293 K
γ = 112.754 (8)°Block, colourless
V = 608.8 (2) Å30.16 × 0.13 × 0.12 mm
Data collection top
Bruker APEXII CCD
diffractometer
2134 reflections with I > 2σ(I)
φ and ω scansRint = 0.030
Absorption correction: multi-scan
(PLATON; Spek, 2020)
θmax = 26.0°, θmin = 3.1°
Tmin = 0.692, Tmax = 0.746h = 99
28088 measured reflectionsk = 1010
2390 independent reflectionsl = 1313
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.033 w = 1/[σ2(Fo2) + (0.0316P)2 + 0.2822P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.085(Δ/σ)max = 0.001
S = 1.06Δρmax = 0.25 e Å3
2390 reflectionsΔρmin = 0.22 e Å3
173 parametersExtinction correction: SHELXL2018 (Sheldrick, 2015a), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.049 (4)
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F11.08584 (18)0.27078 (19)1.04625 (12)0.0741 (4)
S10.24164 (6)0.03934 (6)0.75602 (5)0.04823 (16)
C90.4981 (2)0.1126 (2)0.84284 (15)0.0387 (3)
N10.24898 (19)0.19405 (16)0.65697 (13)0.0392 (3)
O20.2293 (2)0.04387 (15)0.46792 (13)0.0545 (3)
C30.2391 (2)0.33495 (19)0.47696 (15)0.0363 (3)
C20.2496 (2)0.44593 (19)0.57772 (16)0.0377 (3)
C40.2384 (2)0.17202 (19)0.52546 (15)0.0371 (3)
C140.6203 (3)0.0477 (2)0.80124 (16)0.0437 (4)
H140.5683900.0317040.7269270.052*
C10.2542 (2)0.3584 (2)0.69453 (16)0.0426 (4)
C100.5759 (3)0.2315 (2)0.95385 (16)0.0477 (4)
H100.4939700.2746540.9819950.057*
C130.8189 (3)0.1008 (2)0.87014 (18)0.0494 (4)
H130.9018800.0577550.8433280.059*
O10.2617 (2)0.40926 (19)0.80103 (13)0.0677 (4)
C50.2537 (2)0.6089 (2)0.55945 (19)0.0480 (4)
H50.2607880.6838510.6267450.058*
C80.2312 (2)0.3813 (2)0.35505 (17)0.0457 (4)
H80.2236300.3061830.2877290.055*
C60.2467 (3)0.6564 (2)0.4369 (2)0.0537 (5)
H60.2499230.7653880.4219910.064*
C120.8907 (3)0.2184 (2)0.97887 (16)0.0481 (4)
C70.2351 (3)0.5449 (2)0.33686 (19)0.0530 (5)
H70.2298070.5798360.2557000.064*
C110.7746 (3)0.2856 (2)1.02229 (17)0.0527 (4)
H110.8285170.3658831.0962130.063*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0543 (7)0.1016 (10)0.0582 (7)0.0325 (7)0.0002 (5)0.0060 (6)
S10.0412 (2)0.0455 (3)0.0608 (3)0.01677 (19)0.0191 (2)0.0183 (2)
C90.0441 (8)0.0374 (8)0.0414 (8)0.0196 (7)0.0179 (7)0.0137 (6)
N10.0398 (7)0.0356 (7)0.0453 (7)0.0184 (6)0.0121 (6)0.0053 (5)
O20.0691 (8)0.0373 (6)0.0608 (8)0.0255 (6)0.0189 (6)0.0032 (5)
C30.0279 (7)0.0316 (7)0.0456 (8)0.0112 (6)0.0058 (6)0.0004 (6)
C20.0280 (7)0.0336 (7)0.0497 (9)0.0135 (6)0.0062 (6)0.0002 (6)
C40.0315 (7)0.0329 (7)0.0453 (8)0.0130 (6)0.0086 (6)0.0004 (6)
C140.0492 (9)0.0394 (8)0.0458 (9)0.0198 (7)0.0161 (7)0.0015 (7)
C10.0396 (8)0.0431 (9)0.0480 (9)0.0215 (7)0.0102 (7)0.0016 (7)
C100.0627 (11)0.0534 (10)0.0427 (9)0.0347 (9)0.0229 (8)0.0104 (8)
C130.0513 (10)0.0541 (10)0.0542 (10)0.0300 (8)0.0203 (8)0.0078 (8)
O10.0969 (11)0.0733 (9)0.0502 (8)0.0506 (9)0.0245 (7)0.0001 (7)
C50.0386 (9)0.0340 (8)0.0699 (12)0.0167 (7)0.0102 (8)0.0031 (8)
C80.0420 (9)0.0445 (9)0.0459 (9)0.0149 (7)0.0085 (7)0.0043 (7)
C60.0397 (9)0.0357 (9)0.0847 (14)0.0165 (7)0.0127 (9)0.0173 (9)
C120.0476 (10)0.0564 (10)0.0407 (9)0.0230 (8)0.0091 (7)0.0125 (8)
C70.0426 (9)0.0517 (10)0.0606 (11)0.0166 (8)0.0100 (8)0.0195 (9)
C110.0674 (12)0.0562 (11)0.0367 (9)0.0291 (9)0.0117 (8)0.0020 (8)
Geometric parameters (Å, º) top
F1—C121.357 (2)C2—C51.385 (2)
S1—N11.7031 (14)C2—C11.480 (2)
S1—C91.7744 (17)C14—C131.382 (2)
C9—C141.388 (2)C1—O11.200 (2)
C9—C101.391 (2)C10—C111.380 (3)
N1—C41.409 (2)C13—C121.370 (3)
N1—C11.419 (2)C5—C61.390 (3)
O2—C41.2042 (19)C8—C71.389 (2)
C3—C81.379 (2)C6—C71.380 (3)
C3—C21.386 (2)C12—C111.369 (3)
C3—C41.483 (2)
N1—S1—C9101.48 (7)N1—C4—C3105.85 (12)
C14—C9—C10119.94 (16)C13—C14—C9120.07 (16)
C14—C9—S1119.73 (13)O1—C1—N1124.67 (16)
C10—C9—S1120.32 (13)O1—C1—C2129.59 (16)
C4—N1—C1111.15 (13)N1—C1—C2105.74 (13)
C4—N1—S1124.57 (11)C11—C10—C9120.05 (16)
C1—N1—S1124.18 (12)C12—C13—C14118.46 (16)
C8—C3—C2121.71 (15)C2—C5—C6117.57 (16)
C8—C3—C4129.67 (15)C3—C8—C7117.33 (17)
C2—C3—C4108.63 (14)C7—C6—C5121.21 (16)
C5—C2—C3120.89 (16)F1—C12—C11118.60 (16)
C5—C2—C1130.49 (15)F1—C12—C13118.40 (16)
C3—C2—C1108.62 (13)C11—C12—C13122.99 (17)
O2—C4—N1125.15 (15)C6—C7—C8121.29 (18)
O2—C4—C3129.00 (16)C12—C11—C10118.49 (17)
N1—S1—C9—C1494.43 (14)S1—N1—C1—C2177.35 (10)
N1—S1—C9—C1087.09 (14)C5—C2—C1—O10.3 (3)
C9—S1—N1—C4102.84 (13)C3—C2—C1—O1179.48 (18)
C9—S1—N1—C181.20 (14)C5—C2—C1—N1179.31 (15)
C8—C3—C2—C50.3 (2)C3—C2—C1—N10.90 (17)
C4—C3—C2—C5179.63 (13)C14—C9—C10—C110.3 (2)
C8—C3—C2—C1179.50 (14)S1—C9—C10—C11178.80 (13)
C4—C3—C2—C10.56 (16)C9—C14—C13—C120.3 (3)
C1—N1—C4—O2178.85 (15)C3—C2—C5—C60.0 (2)
S1—N1—C4—O22.4 (2)C1—C2—C5—C6179.75 (15)
C1—N1—C4—C30.59 (16)C2—C3—C8—C70.3 (2)
S1—N1—C4—C3177.00 (10)C4—C3—C8—C7179.68 (15)
C8—C3—C4—O20.7 (3)C2—C5—C6—C70.3 (3)
C2—C3—C4—O2179.41 (16)C14—C13—C12—F1179.83 (15)
C8—C3—C4—N1179.94 (15)C14—C13—C12—C110.0 (3)
C2—C3—C4—N10.00 (16)C5—C6—C7—C80.4 (3)
C10—C9—C14—C130.1 (2)C3—C8—C7—C60.1 (3)
S1—C9—C14—C13178.37 (13)F1—C12—C11—C10179.74 (16)
C4—N1—C1—O1179.44 (16)C13—C12—C11—C100.5 (3)
S1—N1—C1—O13.0 (2)C9—C10—C11—C120.6 (3)
C4—N1—C1—C20.91 (17)
Quantum chemical parameters calculated at the B3LYP/6-311G(d,p) level for FP top
Quantum chemical parameterseV
ELUMO-2.54
EHOMO-7.06
ΔE = ELUMOEHOMO4.58
Υ = -ELUMO2.54
I = -EHOMO7.06
φ = Y+1/24.80
Ψ = 1-Y/22.26
S = 1/Ψ0.44
ω = φ2/2Ψ4.44
ε = 1/ω0.23
ω+ = (I+3\Y)2/16(I-Y)2.94
ω- = (3I+\Y)2/16(I-Y)7.68
Δω± = ω+ + ω-10.62
I is the ionization potential, Y is the electron affinity, Φ is the absolute electronegativity, Ψ is the chemical hardness, S is the absolute softness, ω is the electrophilic index, ε is the nucleophilic index, ω+ is the electron-accepting power, ω- is the electron-donating power and Δω± is the net electrophilicity.
Experimental and calculated 1H and 13C NMR spectral data for FP top
AtomExperimentalCalculated
H17.23–7.307.18
H27.31–7.338.22
H37.89-7.918.01
H47.76–7.787.92
C1148.7174.53
C2118.5121.41
C3128.7146.91
C4144.0141.27
C5170.0173.57
C6130.7137.36
C7126.1129.65
C8133.9140.84
The physicochemical properties, druglikeness and the pharmacological properties with SwissADME prediction of the compounds top
Physicochemical propertiesDruglikenessPharmacokinetic properties
MW285.38WLogP3.13GIHigh
H-A3ILOGP2.53BBBYes
H-D0XLOGP32.90P-gp substrateNo
TPSA62.68SA3.91CYP1A2 inhibitorNo
Rotatable bonds2LogS-3.30
MR77.92CYP2D6 inhibitorNo
Fraction C(sp3)0.86LogKp-5.98
N(atoms)19
MW is the molecular weight (g mol-1), H-A is the number of hydrogen-bond acceptors, H-D is the number of hydrogen-bond donors, LogS is the solubility, TPSA is the total polar surface area, MR is the molar refractivity, N(atoms) is the number of atoms, WLogP, iLOGP and XLOGP3 are the lipophilicity, SA is the synthetic accessibility, GI is gastrointestinal, BBB is the blood brain barrier, P-gp is P-glycoprotein, CYP1A2 is cytochrome P450 family 1 subfamily A member 2 (PDB entry 2HI4), CYP2D6 is cytochrome P450 family 2 subfamily D member 6 (PDB entry 5TFT) and Log Kp is the skin permeation (cm s-1).
Toxicity prediction values and results for FP and its intermediates calculated by T.E.S.T. and ProTox-II top
Acute toxicityDevelopmental toxicityMutagenicity
Oral rat LD50 (mg kg-)Fat-head minnow LC50 (96 h) (mg l-1)Predicted valuePredicted resultPredicted valuePredicted result
1046,330.490,49Developmental NON-toxicant0.46Negative
Organ toxicityToxicity end points
HepatotoxicityCarcinogenicityImmunotoxicityMutagenicityCytotoxicityLD50 (mg kg-1)
InactiveActiveInactiveInactiveInactive2500
The minimum inhibition concentrations (MICs) of FP and standard drugs top
SampleMIC (µg ml-1)
Gram-staining-positiveGram-staining-negativeFungi
B. subtilisS. aureusE. faecalisE. coliK. pneumoniaeP. aeruginosaA. nigerC. albicans
FP compound102410241024128256256256128
Amoxicillin>1024>1024>1024>1024>1024>1024--
Tetracycline46464646464--
Ketoconazole------12
 

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