Received: 14 August 2017 Revised: 10 October 2017 Accepted: 11 October 2017

FU L L PAP ER

DOI: 10.1002/aoc.4170

Antibacterial, DFT and molecular docking studies of Rh(III)complexes of Coumarinyl‐Thiosemicarbazone nuclei basedligands

Safaa S. Hassan

Department of Chemistry, Faculty ofScience, Cairo University, Giza, Egypt

CorrespondenceSafaa S. Hassan, Department ofChemistry, Faculty of Science, CairoUniversity, Giza, Egypt.Email: safaa_inorgchem@yahoo.com

Appl Organometal Chem. 2017;e4170.https://doi.org/10.1002/aoc.4170

Coumarinyl thiosemicarbazone derivatives (1E)‐1‐(1‐(2‐oxo‐2H‐chromen‐3‐yl)

ethylidene)thiosemicarbazide (OCET), (1E)‐1‐(1‐(6‐bromo‐2‐ oxo‐2H‐chro-

men‐3‐yl)ethylidene)thiosemicarbazide (BOCET) and 1‐(1‐(3‐oxo‐3H‐benzo[f]

chromen‐2‐yl)ethylidene)thiosemicarbazide (NOCET) and their Rh(III) com-

plexes were synthesized, the characterization was carried out by elemental

analysis, IR, UV–Visible, mass, magnetic measurement and molar conduc-

tance techniques. Data interpretation of the Rh(III) complexes indicates that

the ligands of coumarinyl thiosemicarbazone derivatives were formed in stoi-

chiometric ratios as 1:2 (metal: ligand). The studied ligands act as a bidentate

ligand by using both azomethine nitrogen and thiol sulphur as monoanion

center of donation. The theoretical conformational structure analyses were

performed using density functional theory for ligands and complexes at

B3LYP functional with 6‐31G(++)d,p basis set for ligands and LANL2DZ

basis set for complexes. The charge distribution within the ligands and its

Rh(III) complexes was calculated using Mulliken population analysis of

(MPA) and natural population analysis (NPA). The antibacterial activity of

the prepared compounds was tested against some types of Gram positive

and negative bacteria. Molecular docking investigation proved that, the

ligands and complexes had interesting interactions with active site amino

acids of ribosyltransferase (code: 3GEY).

KEYWORDS

3GEY, Coumarin‐yl thiosemicarbazone derivatives, MPA, NPA, Rh(III) complexes

1 | INTRODUCTION

Millions of people worldwide are affected by infectiousdiseases caused by bacteria. Discovering and developmentof novel antibiotics has been driven to a great interest toovercome the resistance of these organisms to the com-mon drugs that usually used against them. This declaresthe seriousness of the effort that must be developed withnew improved effective medicines against this vast arrayof diseases. Coumarin and thiosemicarbazone nuclei are

wileyonlinelibrary.com/journ

the bases for many successful drugs. Coumarincompounds have more than 40 drugs, which are widelyused in medicine[1,2] as seen in (Scheme 1) that contain-ing some of the studied coumarinyl thiosemicarbazonederivatives. So, the crystal structure of new derivativeslike (E)‐1‐[1‐(6‐Bromo‐2‐oxo‐2H‐chromen‐3‐yl)ethyli-dene]thiosemicarbazide was studied.[3] Progresses ofvarious medicinal applications of coumarins metalcomplexes were summarized by several reviews[4,5] asthiosemicarbazone derivative of 3‐acetyl coumarin in

Copyright © 2017 John Wiley & Sons, Ltd.al/aoc 1 of 12

SCHEME 1 Some coumarinyl thiosemicarbazone derivatives

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reducing the toxicity of Aβ peptide in SH‐SY5Y cells bythe inhibition of the higher aggregate formation.[6]

Coumarin nucleus and related derivatives have aconsiderable biological activity like vasodilatory andantithrombotic,[7] antibacterial,[8] antimutagenic,[9]

inhibition of cyclooxygenase and lipoxygenase,[10,11]

scavenging for reactive oxygen species andntiumourigenic.[12,13] The coordination of many couma-rin derivatives to the metal ions caused a great enhance-ment of the biological activity results as it was reportedin the literature.[14,15] Generally, the enhancement ofthe complexes activities is ascribed to the synergisticimpact which grows their lipophilicity.[16,17] Also, themetal thiosemicarbazone complexes give higher biologi-cal activities than the thiosemicarbazone compoundsitself. The interesting chemical properties exhibited bythe complexes of rhodium metal encourage the largeconsiderable current attention of rhodium chemis-try.[18,19] With all of the above, the target of the currentwork was to examine the effect of some novel Rh(III)complexes of coumarinyl thiosemicarbazone compounds(Scheme 1 (A‐C)) as possible antibacterial agents withthe performing of the molecular docking studyRibosyltransferase that is the target enzyme for thedocking studies.[20]

2 | EXPERIMENTAL

RhCl3 3H2O and all other chemicals were purchased fromSigma Company.

2.1 | Synthesis of the Schiff base ligandsand their Rh(III) complexes

2.1.1 | Schiff base ligands

Coumarin thiosemicarbazone Schiff base ligands, (1E)‐1‐(1‐(2‐oxo‐2H‐chromen‐3‐yl)ethylidene)thiosemicarbazide(OCET), (1E)‐1‐(1‐(6‐bromo‐2‐oxo‐2H‐chromen‐3‐yl)ethylidene)thiosemicarbazide (BOCET) and 1‐(1‐(3‐oxo‐3H‐benzo[f]chromen‐2‐yl)ethylidene)thiosemicarbazide(NOCET) were synthesized according to the knowncondensation method.[21]

2.1.2 | Rh(III) complexes

Rh(III) complexes were synthesized by mixing Rh(III)chloride (1.0 mmol, in 20 ml ethanol/water (50:50) vol-ume to a hot solution of each thiosemicarbazone ligand(2.0 mmol, in 30 ml ethanol). The resulted solution wasrefluxed for 1 h under stirring. By evaporation method,we reduced the volume of the resulted solution to its half.The colored red precipitate complexes were filtered andwashed with ethanol /water (1:1) and finally dried undervacuum.

2.2 | Analyses and biologicalmeasurements

(C, H and N) analyses were carried out by standard micro-analysis techniques using automatic analyzer CHNSVario EL III‐Elementar, Germany at Microanalyticalcenter, Cairo University, Giza, Egypt. The conductivity

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meter ORION model 150 of 0.6 cells constant was used tomeasure the molar conductivity of the synthesized com-plexes through the preparation of 10‐3 M solutions usingDMF as solvent. FT‐IR spectra were obtained with KBrdisc technique using scan Shimadzu FTIR spectrometer;the spectra were collected in the range 200‐4000 cm‐1.The electronic absorption spectra in DMSO were mea-sured using automated UV/Vis‐ NIR 3101 PC Shimadzuspectrophotometer ranged from 200‐900 nm. The molarmagnetic susceptibility of the complexes was measuredat room temperature on prepared samples using a mag-netic susceptibility Cambridge, England Sherwood Scien-tific. The effective magnetic moments were calculatedfrom the expression μeff = 2.828(XM T)1/2 B.M., whereXM is the molar susceptibility corrected using Parcel'sconstants for diamagnetism of all atoms in thecompounds.[22]

A modified Kirby‐Bauer disc diffusion method[23] wasused to determine the antimicrobial activity of the testedsamples. Briefly, 100 μl of the test bacteria were grown in10 ml of Mueller Hinton media until they reached a countof approximately 107 cells/ml for bacteria[24] by using theplate counter. 100 μl of microbial suspension was spreadonto agar plates. Blank paper disks (Schleicher & Schuell,Barcelona, Spain) with a diameter of 8.0 mmwere impreg-nated 10 μl of testing concentration of the stock solutionsand placed on agar media. Gram (+) bacteria as Staphylo-coccus aureus, Bacillus subtilis; Gram (‐) bacteria asEscherichia coli, Pseudomonas aeruginosa were incubatedat 35‐37 °C for 24‐48 hours and then the diameters of theinhibition zones were measured in millimeters.[23]

2.3 | Computational methods

The input files of (OCET), ((BOCET), (NOCET) and theirRh(III) complexes were prepared with GaussView5.0.8.[25] Gaussian 09 rev. A.02[26] was used to make theall calculations by the DFT/B3LYP method. 6‐31G(++)d,p and LANL2DZ are the standard basis sets for the syn-thesized ligands and their Rh(III) complexes respectively.All docking steps were done by MOE 2008 (Molecular

TABLE 1 Analytical and physical data of (OCET), (BOCET), (NOCET

Compound empirical formulaMolecularweight Color

(OCET) C12H11N3O2S 261.3 Yellowish cr

Rh[(C12H10N3O2S)2 cl H2O]. H2O 694.97 Orange

(BOCET) C12H10BrN3O2S 340.2 Yellowish cr

Rh[(C12H9BrN3O2S)2 cl H2O] 834.75 Orange

(NOCET) C16H13N3O2S 311.36 Yellowish cr

Rh[(C16H12N3O2S)2 cl H2O] 777 Orange

Operating Environment) software to simulate the bindingmodel of these compounds into ATP binding sites of3GEY transferase enzyme. The protein crystal structurewas obtained from the Protein Data Bank (PDB).

3 | RESULTS AND DISCUSSION

3.1 | Ligands and their Rh(III)‐bindingsites

The Elemental analyses (C, H & N) for OCET, BOCETand NOCET ligands and their Rh(III) complexes showexcellent agreement between the theoretical and experi-mental values. The analytical data are summarized in(Table 1). The complexes are formed with stoichiometricratio 1:2 (Rh(III): ligand).

3.1.1 | Conductance, infrared and 1HNMRanalysis

The reading of molar conductivity measurements ofRh(III) complexes is (10‐15 ohm‐1 cm2 mol‐1) in anhy-drous DMF. It means the non‐electrolytic in nature ofthe synthesized Rh(III) complexes because the molarconductance is considered as a testing to know thedegree of ionization of the prepared Rh(III) complexes.If the anions (chloride ion) are absent outside the coordi-nation sphere, therefore the non‐molar conductivity ofthe investigated complexes will be detected; thus all theprepared Rh(III) complexes haven’t chloride ionoutside the coordination sphere but is bonded directlyto the Rh(III) center.

Infrared scanning of the free three ligands exhibitsthiol groups vibration at 2676 to 2649 cm‐1 and thionebands at 859, 827 and 821 for OCET, BCET and NCET,respectively[27] indicating that they remain as the thiol‐thione tautomer forms. OCET complex exhibits a broadband at 3423 cm‐1 related to the water of hydrationwhich overlapped the stretching frequency value ofthe amino group. All ligands show bands in the range3388‐3406 cm‐1, assigning the highest absorptions to

) and their Rh(III) complexes

Yield

Found (Calc.) %

C H N

eam 80% 54.16(55.16) 4.0(4.24) 15.3(16.08)

70% 40.57(41.48) 3.69(3.48) 12.09(12.09)

eam 80% 41.0(42.37) 2.5(2.96) 12.1(12.35)

70% 33.5(34.53) 2.3(2.41) 9.7(10.07)

eam 61.20(61.72) 3.95(4.21) 12.5(13.5)

70% 49.7(49.46) 3.30(3.37) 10.03(10.8)

TABLE 3 UV–Vis spectral data

Compound λmax (nm) Assignment

OCET 258 П‐ П*349 n–П*

BOCET 267 П‐ П*357 n–П*

NOCET 265 П‐ П*378 n–П*

Rh‐OCET 344 and 262 [29,069 and38,167 cm‐1]

1A1g to1T1g and

1A1g

to 1T2g732 [13,661 cm‐1] 1A1g to

3T1g211 [47,393 cm‐1]

Rh‐BOCET 28,571 and 350 [28,571 and39,525 cm‐1]

1A1g to1T1g and

1A1g

to 1T2g733 [13,642 cm‐1] 1A1g to

3T1g210 [47,619 cm‐1]

Rh‐NOCET

378 and 254 [26,455 and39,370 cm‐1]

1A1g to1T1g and

1A1g

to 1T2g733 [13,642 cm‐1] 1A1g to

3T1g232 and 205 [43,103 and48,780 cm‐1]

TABLE 2 Infrared spectral data of [(OCET), (BOCET)& (NOCET)] and their Rh(III) complexes (cm‐1)

υ (NH2) υ (=C‐H) υ (‐C‐H)aromatic υ (C = O) υ (H2O)coord. υ (C = N) υ (Rh‐N) υ (Rh‐O) υ (Rh‐S) υ (Rh‐cl)

(OCET) 3388 3153 3044 1719 ‐‐‐‐‐‐ 1603 ‐ ‐ ‐ ‐

Rh‐OCET Overlap 3170 2923 1720 848 1568 589 458 329 277

(BOCET) 3405 3135 2985 1723 ‐‐‐‐‐‐‐ 1590 ‐‐‐ ‐‐‐‐ ‐‐‐‐‐ ‐‐‐‐

Rh‐BOCET 3406 3148 2926 1721 772 1560 583 552 389 263

(NOCET) 3404 3154 2946 1714 ‐‐‐‐‐‐‐‐‐‐ 1593 ‐‐‐‐ ‐‐‐‐ ‐‐‐‐‐‐‐‐ ‐‐‐‐‐‐‐‐‐

Rh‐NOCET

3403 3172 2957 1715 710 1581 560 420 375 282

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υ(sym) stretching frequencies for NH2 groups withoutany shift upon complexation in their stretching frequen-cies meaning that the NH2 groups still free aftercomplexation. The disappearance of both thiol ν(SH)and thione ν(C = S) vibrations[28] upon complexationin all Rh(III) complexes can be explained in terms ofcoordination through the mononegatively charged sulfuratom which supported by non‐electrolytic properties ofthe complexes. The clear shift of the υ (C = N) vibrationto a lower value by complexation may be assigned tothe coordination between the Rhodium ion and theazomethine nitrogen. The presence of coordinatedwater was confirmed by the medium strength bandsat 848–710 cm–1.[29] The band positions of thecarbonyl groups not changed after complexation, so car-bonyl oxygen atom hasn't a role in the complexationprocess. New bands are formed due to (M‐N), (M‐O),(M‐S) and (M‐Cl) bonds [18–31] as shown with the mostimportant characteristic bands in (Table 2).

The 1H NMR spectrum of the (OCET, BOCET &NOCET) ligands and their Rh(III) complexes in DMSOshows signals at

OCET: [7.36–7.97 (5H, Ar.), 3.37(3H, methyl), 10.48‐(H, NH) and 8.43(2H, NH2)], BOCET: [7.38–7.97 (5H,Ar.), [3.28(3H, methyl), 10.42(H, NH) and 8.40(2H, NH2)],

NOCET: [7.40–7.97 (5H, Ar.), 3.41(3H, methyl),10.54(H, NH) and 8.48(2H, NH2)],

Rh‐OCET: [7.43–8.05 (5H, Ar.), 3.88(3H, methyl) and9.0(2H, NH2)],

Rh‐BOCET: [7.45–8.31 (5H, Ar.), 3.84(3H, methyl)and 9.0(2H, NH2)] and

Rh‐NOCET: [7.35–8.64 (5H, Ar.), 3.60(3H, methyl)and 8.64(2H, NH2)].

The deuterated (D2O) spectrum of each ligand pointedout that the signal corresponding to the NH group ofligand was disappeared, it indicates the lability of theproton of the NH group.

By the absence of the band corresponding to the NHgroup after each complex formation,[32] it supports thecoordination via the thiol formation tautomer as shownin the IR discussion.

3.1.2 | Magnetic and electronic spectralstudies

The magnetic moment values of Rh(III) complexes arevery small less than 0.3 B.M. with all studying ligandscorrespond to octahedral stereochemistry with diamag-netic nature.[33]

The most important electronic spectra of the preparedligands and their Rhodium complexes were carried out inDMSO at room temperature as declared in (Table 3). Thebands of ligands in the region 258‐267 nm can be assigneddue to π‐ π* specifically the aromatic part. The bands inthe region 349‐378 nm due to n ‐ π* transition of thenon‐bonding electrons of (C = S), (C = O) andazomethine (C = N)[34] groups of ligands. For Rh(III)complexes, the two absorption bands observed at 26455 ‐

29069 and 38.167 ‐ 39,525 cm‐1 are related to the two spinallowed transitions: 1A1g to

1T1g and1A1g to

1T2g, respec-tively.[33] The bands calculated at 13642 ‐ 13661 cm‐1 can

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be attributed due to 1A1g to3T1g transitions, whereas the

bands beyond 40000 cm‐1 are the charge transfer kind,indicating[35] Rh(III) ion distorted octahedralstereochemistry.

3.1.3 | Mass spectra study

Mass spectra of the Rh(III) complexes are confirmed asshown in (Figure 1 a‐c). It confirms the suggested struc-ture geometry as shown in (Figure 2).

3.1.4 | Geometric study

The geometric optimization is carried out for the differentthiosemicabazone ligands in the thiol form which was

(a) Mass spectra of the Rh [(C12H10

(b) Mass spectra of the Rh [(C12H

(c) Mass spectra of the Rh [(C16

FIGURE 1 (a) Mass spectra of the Rh[(C12H10N3O2S)2 cl H2O].H2O co

(c) Mass spectra of the Rh[(C16H12N3O2S)2Cl.H2O] complex

confirmed in the previous characterization part and theirRh(III) complexes as seen in (Figure 3) with the number-ing system. The optimization energy, dipole moment,energy gap and hardness(η) values are mentioned in(Table 4). The ligands energy values indicated that thepresence of bromo derivative and fused benzene ringincreases the stability of the cumarine thiosemicarbazonenucleus due to resonance increasing as pointed out in(Figure 4). The reactivity of the complexes under studyfollows the order Rh[(NOCET)2 Cl H2O] > Rh[(BOCET)2Cl H2O] > Rh[(OCET)2 Cl H2O], as the energy gap of thestudied complexes decreases, the reactivity of the Rh(III)complexes increases. The polarity of the ligands increasedafter complexation by their coordination to Rh(III) ion asit is evident from the magnitude of their dipole moments.

N3O2S)2 Cl H2O] . H2O complex

9BrN3O2S)2Cl H2O] complex

H12N3O2S)2Cl.H2O] complex

mplex. (b) Mass spectra of the Rh[(C12H9BrN3O2S)2ClH2O]complex.

FIGURE 2 The suggested structure of the complexes

TABLE 4 Ground state properties, HOMO–LUMO energy, hardness, i

BOCET and NOCET using B3LYP/6‐31G(++)d,p and Rh(III) complexes

Parameter OCETRh[(OCET)2 ClH2O]

ET, Hartree ‐1176.8214 ‐1776.8599

EHOMO, eV ‐0.21305 ‐0.18620

ELUMO, eV ‐0.08797 ‐0.10051

E*g, eV 3.4036 2.331 7

Hardness = 1/2 (E LUMO‐ E HOMO) 1.7018 1.1658

μ, dipole moment (Debye) 4.2375 8.3176

I.E = ‐ E HOMO, eV 0.21305 0.18620

EA = ‐ E LUMO, eV 0.08797 0.10051

*Eg = ELUMO ‐ EHOMO.

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The geometric changes that are noticed in thestudied ligand moiety itself are interesting. Thus, mostof bond lengths are increased upon complexation withthe metal ions. Analysis of the data calculated for thebond lengths (Table 5), we can conclude that C17‐N22,C24‐S28, N22‐N23 and C24‐N23 bond lengths becomelonger in all complexes, as the coordination takes placevia N atoms of the (C = N) azomethine[36] and the sulfurof the deprotonated thiol group. This finding is due tothe formation of the M‐S and M‐N bonds, that makethe C‐S and C‐N bonds weaker.[36] The bond angles ofthe ligands are altered relatively upon coordination.The atomic charge distribution of the thiol form of the

FIGURE 3 Optimized geometry of

(OCET, BOCET & NOCET) ligands and

their Rh(III) complexes

onization energy, dipole moment and electron affinity of the OCET,

using B3LYP/LANL2DZ

BOCETRh[(BOCET)2 ClH2O] NOCET

Rh[(NOCET)2 ClH2O]

‐3747.9488 ‐1801.9665 ‐1330.4745 ‐2084.100

‐0.21956 ‐0.19225 ‐0.21775 ‐0.18405

‐0.09645 ‐0.10986 ‐0.09173 ‐0.10233

3.3499 2.241 9 3.429 18 2.223 7

1.6749 1.1209 1.7145 1.1118

3.1735 6.3030 4.9090 8.9222

0.21956 0.19225 0.21775 0.18405

0.09645 0.10986 0.09173 0.10233

FIGURE 4 Energy values diagram of OCET, BOCET and NOCET

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ligands and their Rh(III) complexes is determined byMulliken (MPA) and natural (NPA) population analysis.The results for the selected atoms are presented in(Table 6). The distribution of positive and negativecharges is important from the perspective of increase ordecrease in the bond length between atoms. In theNBO analysis, the results show that the most negativeatomic charges are related to nitrogen (22) atoms in

TABLE 5 Some of the optimized bond length, Å and bond angles, degr

Rh(III) complexes using B3LYP/LANL2DZ

Bond length (Å) OCET Rh[(OCET)2 Cl H2O] BOCET

C24‐S28 1.77601 1.83694 1.77462

C24‐N23 1.31172 1.31245 1.31148

N22‐N23 1.36212 1.40626 1.36153

C17‐N22 1.29579 1.32679 1.29610

C24‐N25 1.35671 1.37344 1.36047

C3‐C17 1.47641 1.48170 1.47591

Rh‐S28 ‐‐‐ 2.76108 ‐‐‐

Rh‐O31 ‐‐‐ 2.35214 ‐‐‐

Rh‐Cl30 ‐‐‐ 2.69745 ‐‐‐

Rh‐N22 ‐‐‐ 2.42272 ‐‐‐

Bond angles (deg.)

S28‐C24‐N23 125.676 127.434 12

N23‐N22‐C17 118.698 112.129 11

N22‐C17‐C3 117.481 118.970 11

N22‐Rh29‐S28 74.088 ‐‐‐ ‐‐

N55‐Rh29‐S61 78.820 ‐‐‐ ‐‐

N22‐Rh29‐O31 92.653 ‐‐‐ ‐‐

N55‐Rh29‐Cl30 84.282 ‐‐‐ ‐‐

N22‐Rh29‐Cl30 96.955 ‐‐‐ ‐‐

S28‐Rh29‐Cl30 63.409 ‐‐‐ ‐‐

O31‐Rh29‐Cl30 141.198 ‐‐‐ ‐‐

N22‐Rh29‐N55 177.750 ‐‐‐ ‐‐

S28‐Rh29‐S61 164.008 ‐‐‐ ‐‐

the studied ligands (OCET, BOCET and NOCET) andto nitrogen and sulfur (after deprotonation) atoms intheir Rh(III) complexes. Upon chelation the charge ofthe nitrogen atom has a slight decrease in its negativevalue with the decreasing in the remaining surroundingatoms relative to the ligands because of the involvementof nitrogen atom in coordination to the Rh(III) atomwith electron back–donation from the metal ion to thedonating nitrogen site.[37] The cloud density on Sincreases after deprotonation of the thiol group withthe decrease of the electron densities of the neighboringatoms because the coordination of the sulfur atom asmononegatively charged atom. The oxygen electrondensity of the water molecule was decreased uponcomplexation from (‐0.976) to [‐0.940 (OCET), ‐0.824(BOCET) & ‐0.940 (NOCET)] corresponding to the unco-ordinated and the coordinated water states respectively,this is due to ligand to metal charge transfer (L → M).The electron density on Rh atom center increases aftercomplexation because the charge transfer from theexamined ligand to the central Rh ion i.e. L → M. So,

ees, for OCET, BOCET and NOCET using B3LYP/6‐31G(++)d,p and

Rh[(BOCET)2 Cl H2O] NOCET Rh[(NOCET)2 Cl H2O]

1.83791 1.78491 1.83440

1.31259 1.29928 1.31209

1.40594 1.37484 1.40779

1.32644 1.29726 1.32765

1.37259 1.36863 1.37442

1.48256 1.48242 1.48189

2.75822 ‐‐‐ 2.74705

2.35742 ‐‐‐ 2.36811

2.69102 ‐‐‐ 2.69432

2.42576 ‐‐‐ 2.41916

5.821 127.429 126.201 127.547

8.538 112.050 116.111 111.677

7.428 119.066 115.190 120.181

‐ 74.187 ‐‐‐ 74.801

‐ 78.833 ‐‐‐ 78.945

‐ 91.248 ‐‐‐ 89.837

‐ 84.851 ‐‐‐ 85.017

‐ 97.003 ‐‐‐ 97.264

‐ 63.411 ‐‐‐ 63.680

‐ 142.030 ‐‐‐ 142.668

‐ 177.637 ‐‐‐ 177.633

‐ 164.271 ‐‐‐ 164.791

TABLE 6 Atomic charges in terms of MPA and NPA of Rh complexes of OCET, BOCET and NOCET using B3LYP/LANL2DZ and ligands

(OCET), (BOCET) and (NOCET) using B3LYP/6‐31G(++)d,p

Element MPA NPA

Rh ‐OCET(OCET)

Rh ‐BOCET(BOCET)

Rh‐NOCET(NOCET)

Rh ‐OCET(OCET)

Rh ‐BOCET(BOCET)

Rh‐NOCET(NOCET)

Rh 0.112 (‐‐‐) 0.108 (‐‐‐) 0.119 (‐‐‐) 0.248 (‐‐‐) 0.386 (‐‐‐) 0.244 (‐‐‐)

O1 ‐0.282 (‐0.379) ‐0.278 (‐0.409) ‐0.276 (‐0.393) ‐0.547 (‐0.501) ‐0.437 (‐0.500) ‐0.543 (‐0.502)

C2 0.104 (0.578) 0.105 (0.736) 0.095 (0.1732) 0.803 (0.797) 0.699 (0.797) 0.799 (0.774)

C3 0.113 (0.476) 0.118 (0.931) 0.114 (0.0200) ‐0.191 (‐0.178) ‐0.203 (‐0.172) ‐0.190 (‐0.189)

C4 ‐0.306 (0.261) ‐0.312 (0.323) ‐0.264 (0.127) ‐0.095 (‐0.130) ‐0.109 (‐0.133) ‐0.099 (‐0.097)

C5 0.373 (0.968) 0.389 (0.017) 0.218 (0.968) ‐0.124 (‐0.149) ‐0.134 (‐0.134) ‐0.108 (‐0.140)

C6 0.171 (‐2.088) 0.167 (‐1.700) 0.164 (‐0.700) 0.364 (0.347) 0.325 (0.346) 0.379 (0.361)

C7 ‐0.342 (‐0.379) ‐0.327 (‐0.205) ‐0.380 (‐0.386) ‐0.240 (‐0.264) ‐0.269 (‐0.249) ‐0.236 (‐0.262)

C8 ‐0.191 (‐0.267) ‐0.135 (‐0.483) ‐0.422 (‐0.263) ‐0.184 (‐0.207) ‐0.220 (‐0.220) ‐0.157 (‐0.175)

C9 ‐0.243 (0.122) ‐0.241 (‐0.196) 0.387 (0.283) ‐0.224 (‐0.251) ‐0.145 (‐0.138) ‐0.061 (‐0.066)

C10 ‐0.370 (0.206) ‐0.286 (0.426) 0.146 (1.016) ‐0.163 (‐0.191) ‐0.195 (‐0.207) ‐0.022 (‐0.019)

O16 ‐0.229 (‐0.407) ‐0.222 (‐0.366) ‐0.232 (‐0.419) ‐0.578 (‐0.566) ‐0.482 (‐0.560) ‐0.583 (‐0.574)

C17 0.179 (0.045) 0.175 (0.213) 0.167 (‐0.220) 0.357 (0.226) 0.296 (0.226) 0.359 (0.255)

C18 ‐0.694 (‐0.357) ‐0.691 (‐0.579) ‐0.697 (‐0.489) ‐0.677 (‐0.722) ‐0.725 (‐0.722) ‐0.675 (‐0.709)

N22 ‐0.167 (‐0.323) ‐0.164 (‐0.193) ‐0.176 (‐0.290) ‐0.281 (‐0.281) ‐0.229 (‐0.279) ‐0.283 (‐0.315)

N55 ‐0.118 (‐‐‐) ‐0.120 (‐‐‐) ‐0.117 (‐‐‐) ‐0.250 (‐‐‐) ‐0.205 (‐‐‐) ‐0.250 (‐‐‐)

N23 ‐0.017 (‐0.029) ‐0.016 (‐0.135) ‐0.013 (‐0.115) ‐0.415 (‐0.431) ‐0.383 (‐0.427) 0.417 (‐0.422)

C24 ‐0.119 (‐0.043) ‐0.117 (‐0.083) ‐0.119 (‐0.018) 0.359 (0.290) 0.309 (0.289) 0.357 (0.281)

N25 ‐0.573 (‐0.369) ‐0.572 (‐0.324) ‐0.574 (‐0.350) ‐0.828 (‐0.833) ‐0.794 (‐0.831) ‐0.829 (‐0.848)

S28 0.013 (0.082) 0.011 (0.076) 0.013 (0.059) ‐0.127 (‐0.015) ‐0.170 (‐0.008) ‐0.124 (‐0.008)

S61 ‐0.013 (‐‐‐) ‐0.013 (‐‐‐) ‐0.011 (‐‐‐) 0.064 (‐‐‐) ‐0.109 (‐‐‐) ‐0.065 (‐‐‐)

O31(H2O) ‐0.713 (‐‐‐) ‐0.715 (‐‐‐) ‐0.734 (‐‐‐) ‐0.940 (‐‐‐) ‐0.824 (‐‐‐) ‐0.945 (‐‐‐)

Cl ‐0.242 (‐‐‐) ‐0.235 (‐‐‐) ‐0.244 (‐‐‐) ‐0.365 (‐‐‐) ‐0.420 (‐‐‐) ‐0.361 (‐‐‐)

Br13 ‐‐‐ (‐‐‐) ‐0.027 (0.01) ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) 0.076 (0.074) ‐‐‐ (‐‐‐)

C11 ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.372 (‐0.335) ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.194 (‐0.207)

C12 ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.259 (‐0.301) ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.195 (‐0.223)

C13 ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.170 (‐0.182) ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.211 (‐0.238)

C14 ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.419 (‐0.162) ‐‐‐ (‐‐‐) ‐‐‐ (‐‐‐) ‐0.189 (‐0.201)

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the theoretical calculations confirm the results thatobtained from the analysis tools which were discussedin the previous characterization part, Rh (III) ionattached to the ligand via N, O (H2O) and Sdonor atoms. The generated molecular orbital energydiagrams ‐ HOMO, LUMO are presented (Figure 5).

3.2 | Microbiological and dockinginvestigations

By testing the previous investigated ligands and their Rh(III) complexes against different types of bacteriaorganisms, it leads to the ability of the evaluation of

their biological potential. The organisms used in thepresent examinations consists of two of each Gram pos-itive and Gram negative types. The outcomes ofantibacterial actives in vitro of the synthesized ligandswith all their Rh(III) complexes are seen in (Table 7).The marked antibacterial activity results of all examinedcompounds may be due to the chance of the formationof hydrogen bonds through the toxophorically importantimine groups (‐C = N) with the active center of cellconstituents, thereby causing considerable interferencewith normal cell process.[38,39] Also, other importantfunction groups as amino (‐NH2) and oxygen watermolecules are important groups as expected from the

FIGURE 5 Molecular graphs of Rh(III) complexes of OCET, BOCET and NOCET, respectively

TABLE 7 Antibacterial activity data of (OCET, BOCET and NOCET) ligands and their Rh(III) complexes, inhibition zone (mm)

Sample

Inhibition zone diameter(mm/mg sample)

Bacteria

Escherichia coli(G‐)

Pseudo Monas Aeruginosa(G‐)

Bacillus Subtilis (G+)

Staphylococcus aureus (G+)

Control: DMSO 0.0 0.0 0.0 0.0

(OCET) 14 13 13 14

[Rh(OCET)2(H2O)cl] 12 11 9 14

(BOCET) 12 10 11 10

[Rh(BOCET)2(H2O)cl]

11 11 10 12

(NOCET) 9 0.0 0.0 0.0

[Rh(NOCET)2(H2O)cl]

11 10 9 12

HASSAN 9 of 12

docking results (Figure 6). The ligands and their Rh(III)complexes have interesting interactions with active siteamino acids of ribosyltransferase (code: 3GEY) as bothpolar and arene type bonds. The –NH‐ of the aminogroup helped to form polar binding interaction withSerA543, SerA563, CysA556, AspA450 and ThrA539 inOCET, NOCET, Rh‐OCET, Rh‐BOCET and Rh‐NOCET,respectively. The azomethine group ‐C = N forms bind-ing interaction with TyrA582 in BOCET. The oxygen ofthe coordinated water molecules forms hydrogen bondswith AspA540 in Rh‐OCET and CysA556 in Rh‐NOCET.The interactions of arene ‐arene with TyrA582 in bothOCET and Rh‐BOCET and with TyrA569 in Rh‐NOCET.Classically, the polarity of a substance can be indicatedby its dipole moment property. It has been describedthat the drug solubility in water increases withincreasing its dipole moment, i.e. dipole moment is an

important criteria for deciding the penetration of thedrug through the cell membrane of the organism andfor the speed of excretion. The liposolubility of the com-pound increases with decreasing of the dipole moment,thereby favors its permeation through the lipid layer ofthe microorganism more efficiently,[40] consequentlydevastating them more aggressively, which means thatthe less polar drug, assisting in the penetration of thecell wall, and then shifting to the more toxic drugwithin the cellular environment,[41] OCET and BOCETligands have the lower dipole moment values thanNOCET, so both have the higher antibacterial effectsas described in (Figure 7). Rh(OCET) and Rh(BOCET)have the higher antibacterial effect, although thatRh(NOCET) is a comparable antibacterial effect to themdue to Rh(NOCET) have the lower Eg value, i.e. it hashigher reactivity than the other two complexes, due

FIGURE 6 Docking results of (OCET, BOCET & NOCET) ligands and their Rh(III) complexes

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FIGURE 7 Biological activity of ligands and their rh(iii)

complexes towards different types of bacterial strains

HASSAN 11 of 12

to the small difference between the HOMO and LUMOenergy values, this is in accordance with the docu-mented values in literature.[42]

4 | CONCLUSIONS

The structures of Rh(III) complexes of Schiff basesof coumarinyl thiosemicarbazone derivatives wereinterpreted by physicochemical tools. It was found thatthe ligands are a uninegatively bidentate ligands, attachedto the Rh(III) ions as 1:2 (M:L) complexes via azomethineN and deprotonated thiol S with the formation ofdistorted octahedral structure. DFT calculation wascarried out for the prepared three ligands and theirRh(III) complexes with the calculation of charge distribu-tion within the ligands and their Rh(III) complexes usingMulliken population analysis (MPA) and natural popula-tion analysis (NPA). The synthesized ligands and theirRh(III) complexes, had a satisfactory spectrum fortheir antibacterial activity against bacterial species, E. coli& P. aeruginosa as Gram negative and B. subtilis & S.aureus as Gram positive. The docking stimulation pointedout the binding model of OCET, BOCET and NOCET asfree ligands and as Rh(III) complexes. The interactionswith active site amino acids of ribosyltransferase (code:3GEY) involved the hydrogen bond formation andarene‐arene interaction. So, the current findings providea new chance for the development and discovering ofnovel antimicrobials to beat the ever increasing drugresistance problem.

ORCID

Safaa S. Hassan http://orcid.org/0000-0003-1177-2375

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How to cite this article: Hassan SS.Antibacterial, DFT and molecular docking studiesof Rh(III) complexes of Coumarinyl‐Thiosemicarbazone nuclei based ligands. ApplOrganometal Chem. 2017;e4170. https://doi.org/10.1002/aoc.4170