Synthesis, characterization and computational studies

Journal of Molecular Liquids 272 (2018) 481–495

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Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq

Synthesis, characterization and computational studies of semicarbazide derivative M. Muthukkumar a,⁎, T. Bhuvaneswari a, G. Venkatesh b, C. Kamal c, P. Vennila d, Stevan Armaković e, Sanja J. Armaković f, Y. Sheena Mary g, C. Yohannan Panicker g a

Department of Chemistry, Selvam Arts and Science College, Namakkal, Tamilnadu, India Department of Chemistry, VSA Group of Institutions, Salem, Tamilnadu 636010, India Department of Chemistry, Mahendra Engineering College, Namakkal - 637503, Tamil Nadu, India d Department of Chemistry, Thiruvalluvar Government Arts College, Rasipuram 637 401, India e University of Novi Sad, Faculty of Sciences, Department of Physics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia f University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad, Serbia g Department of Physics, Fatima Mata National College, Kollam, Kerala 691001, India b c

a r t i c l e

i n f o

Article history: Received 15 March 2018 Received in revised form 13 June 2018 Accepted 25 September 2018 Available online 26 September 2018 Keywords: Molecular dynamics simulations Bond dissociation energies Molecular docking Geometrical parameters Fukui functions

a b s t r a c t The (E) 1 (3, 5 dibromo benzylidene) semicarbazide (35DBBS) has been synthesized and characterized using Fourier-transform infrared (FT-IR), Fourier transform Raman (FT-Raman), 1H and 13C Nuclear magnetic resonance (NMR) spectral analyzes. Fukui functions, molecular electrostatic potential (MEP), bond dissociation energies (BDE) and average local ionization energy (ALIE) values have been studied with help of Density Functional Theory (DFT). Further, the stability of 35DBBS in water has been analyzed using molecular dynamics (MD) simulations. The optimized molecular geometrical parameters such as bond length, bond angle and dihedral angle were calculated in different phases viz., gaseous and aqueous and were compared with experimental values. The title compound's binding energy and antifungal ability of the title compound were evaluated using molecular docking studies. Further, Nonlinear Optical Properties (NLO) of 35DBBS have been examined by fi rst order hyperpolarizability studies. © 2018 Published by Elsevier B.V.

1. Introduction Semicarbazide derivatives are of centre of attraction since, they have widest biological activities and being a main part of several kinds of significant drug molecules [1–3]. They are tridentate ligands and acted as O, N and O-donors. Semicarbazones and their derivatives play a vital role in organic and medicinal chemistry. They are mainly used in drug design and possess various biological activities namely antifungal, antibacterial, anticonvulsant, antiproliferative, cardio protective antihelmintic, antifungal, antimicrobial, antiinflammatory, antitubercular, antiviral, anticancer, antiplatelet and antischistosomiasis etc. The biological importance of these semicarbazone turned the researchers towards the synthesis and biological evaluation of derivatives of semicarbazones in order to develop excellent therapeutic agents to combat diseases of animals and human beings [1–5]. Some of the hydrazones and semicarbazones exhibited anticonvulsant properties too [6,7]. The presence of lipophilic aryl ring having Cl−, Br− or NO− 2 groups are responsible for the anticonvulsant activity. The occurrence ⁎ Corresponding author. E-mail address: [email protected] (M. Muthukkumar).

https://doi.org/10.1016/j.molliq.2018.09.123 0167-7322/© 2018 Published by Elsevier B.V.

of hydrogen bonding in semicarbazone derivatives has been identified by Dimmock and his co-workers [6]. Aryl semicarbazones possessed greater protection in the maximal electroshock seizure (MES) screen. The reaction for greater protection is the presence of higher electronegative group at the para position of aryl ring. Vibrational spectroscopic analysis is one of the important analytical techniques, which helps in the structural conformation and molecular electronic transition. A DFT approach is a significant method which ensures dynamics information design and deliver of organic drugs. There have been great demands in search of new NLO materials recent past, since the wide range of application such materials in optical computing and communication technologies. Organic NLO materials preferred over inorganic materials due to their applications in optoelectronic technology. Computational quantum-mechanics computations have become indispensable tools for investigation and prediction of various fundamental properties of molecular structures [8–13]. These methods are particularly useful for the investigation of local reactivity properties. In these regards, in this work computational study of local reactivity properties encompassed calculations of molecular electrostatic potential (MEP), average local ionization energy (ALIE), Fukui functions and bond dissociation energies for hydrogen abstraction (H-BDE) have been carried

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M. Muthukkumar et al. / Journal of Molecular Liquids 272 (2018) 481–495

out. Aside of these calculations, we have also investigated the influence of water by molecular dynamics (MD) simulations and calculations of radical distribution functions. Warren et al. synthesized several semicarbazone derivatives which possess antihypertensive activity [1]. Nickel complexes of thiosemicarbazones and semicarbazones have been synthesized by Chandra et al. [14]. Martinez et al. have been synthesized several thiosemicarbazone and semicarbazone compounds [15]. Several biologically significant thiosemicarbazones and semicarbazones were synthesized by Yousef [16]. Kolb et al. have reported the observation of abnormal IR Frequencies of semicarbazones benzaldehyde and acetophenone derivatives [17]. Dhandapani et al. have synthesized (E) 1 (3 methyl 2, 6 diphenyl piperidin 4 ylidene) semicarbazide and studied its structural properties [18]. Subashchandrabose et al. reported the vibrational studies on (E) 1 ((pyridine 2yl)methylene) semicarbazide [19]. Raja et al. [20] have discussed reported the spectral characteristics of (E) 1 (4bromobenzylidene)semicarbazide. The synthesis and chacterization of 1 (substitutedbenzylidene) 4 (4 (2 (methyl/phenyl) 4 oxoquinazolin 3(4H)yl) phenyl) semicarbazide derivatives have been reported by Saravanan et al. [21]. Vital et al. have synthesized semicarbazone, thiosemicarbazone and aminoguanidine derivatives and examined their antitrypanosomal activity [22]. From the literature review, it is clear that, there is no report on experimental and theoretical frequency calculations of (E) 1 (2, 5 dibromo benzylidene) semicarbazide molecules have been reported so far. The detailed literature review has been let us towards the synthesis and characterization 35DBBS. The molecular geometrical parameters, molecular docking, NBO, MEP, global descriptors, vibrational spectra, Fukui functional and Non-liner optics (NLO) properties have been analyzed in the present study. 2. Materials and methods 2.1. Synthesis of 35DBBS 3, 5 dibromobenzaldehyde (1.8 ml, 0.01 mol) is mixed with ethanol (15 ml) and then semicarbazide hydrochloride (1.1 g, 0.01 mol) was added to the reaction mixture. The mixture then stirred for 1 h on magnetic stirrer. Using TLC, the progress of reaction has been continuously monitored. Then ethyl acetate has been added to the reaction mixture to ensure dilution, further dried. The crude solid has been recrystallized using absolute alcohol. The recrystallized solid further dried in vacuum desiccators on fused CaCl2. Fig. 1 is the scheme of synthesis of 35DBBS. 2.2. Experimental The FT-IR spectra of synthesized (E) 1 (3,5 dibromobenzylidene) semicarbazide (35DBBS) were recorded in the region 4000–400 cm−1 in evacuation mode using a KBr pellet technique with 1.0 cm−1 resolution on a PERKIN ELMER FT-IR spectrophotometer. The FT-Raman spectra of the title compound have been recorded in the region 4000–100 cm−1 in a pure mode using Nd: YAG Laser excitation wavelength of Raman 100 mW with 2 cm−1 resolution on a BRUCKER RFS 27 at SAIF, IIT, Chennai, India. 13C and 1H NMR spectra were recorded in DMSO solvent using TMS as an internal standard on a Bruker highresolution NMR spectrometer at 400 MHz.

2.3. Computational details All theoretical computations (quantum chemical calculations) were carried out in Becke3-Lee-Yang-parr (B3LYP) with 6-311++G(d,p) functional using Gaussian 09 W program [23]. The optimized electronic molecular structure of 35DBBS (Fig. 2) is used to predict vibrational frequencies using Gaussian 09 W program and is visualized using Gauss View 5.0.8 program package. The theoretically computed vibrational wavenumbers of 35DBBS are obtained by Vibrational Energy Distribution Analysis (VEDA) program [24]. The calculated vibrational frequencies of 35DBBS calibrated using scaling factor of 0.961 to avoid errors (systematic) caused by incomplete negligence of electron correlation. The NMR chemical shifts (13C and 1H) were calculated with DFT/gauge including atomic orbital (GIAO) using B3LYP/6-311++G(d,p) functional. 2.4. Molecular dynamics (MD) simulations MD simulations of 35DBBS were investigated for its reactive properties in detail. DFT calculations were done with Jaguar [25–29] program, while MD simulation was done with Desmond [29–31] program. Maestro GUI was used for preparation of input files and visualization of results. Jaguar, Desmond and Maestro programs were used as incorporated in Schrödinger Materials Science Suite 2017-4 [32]. For calculations of MEP and ALIE descriptors, a B3LYP/LACV3P++(d,p) basis set was used [33]. Fukui functions and bond dissociation energies for hydrogen abstraction (H-BDE) have been calculated with LACVP +(d) and LACV3P(d,p) basis sets, respectively. OPLS3 [29,33–35] force field was used for MD simulation along with the following set of parameters: simulation time of 10 ns, cut off radius of 12 Å, temperature of 300 K and pressure of 1.0325 bar. The whole system was modeled by placing of one 35DBBS molecule in cubic box, and surrounded with approximately 2500 water molecules. The system was considered as NPT ensemble type. Solvent was considered in the framework of simple point charge (SPC) model [36]. 3. Results and discussion 3.1. Molecular geometry The geometrical parameters viz., bond length, bond angle and dihedral angle were calculated in various phases (gaseous phase and aqueous phase) using B3LYP/6-311++G(d,p) functional level [19–22,37]. The theoretically calculated geometrical parameters were compared with experimental values (Table 1). The calculated geometrical parameters values are slightly deviated with experimental values due to the phase variation. i.e. experimental values were carried out in solid state. 35DBBS molecular structure (Fig. 2) has seven C\\C, four C\\H, two C\\Br, three N\\H & C\\N and one N\\N & C=O bonds. The calculated bond lengths are as follows, C1–C6, C 5–C6 ≈ 1.39 Ǻ, C1–C2, C2–C 3 ≈ 1.38 Ǻ, C4–C5 ≈ 1.37 Ǻ, C 1–C10 ≈ 1.46 Ǻ, C3–Br12, C 5–Br13 ≈ 1.92 Ǻ. From the observation, it is clear that, the aromatic ring is slightly distorted from hexagonal structure, because of substitution effects (C1 –C10, C3–Br12 and C5–Br13). The theoretically calculated bond lengths of C\\H and N\\H are varied as 1.07–1.08 and 0.99–1.0 Ǻ. The calculated bond lengths N14 -N15 ≈ 1.37 Ǻ and C17-O21 ≈ 1.92 Ǻ are well correlated

Fig. 1. Scheme of the synthesis of 35DBBS.


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Fig. 2. Optimized geometrical structure of 35DBBS.

with the experimental values [14–16]. The deviation of calculated bond angles C3-C2-C1 ≈ 119.5°, C 4-C3-C2 ≈ 122.2°, C5-C 4-C3 ≈ 119.1°, C2-C 1C6 ≈ 119.3°, C4-C5-Br13 ≈ 119.1°, C 2-C3-Br12 ≈ 119.2°, N15-C17-O21 ≈ 119.4°, N18-C17-O 21 ≈ 124.5° from 120.0° clearly illustrated the delocalization of electrons in aromatic ring and further, it has been attributed to the presence of higher electronegative bromine in 35DBBS. The observation revealed that, increased bond angles above 120.0° could be due to the hyper-conjugative interactions whereas decreased bond angles below 120.0° might be caused by the interaction between halogens and aromatic ring [16,17]. The experimental values are correlated well with the theoretically calculated values in aqueous phase than gaseous phase. The theoretically calculated dihedral angels C2-C1-C6-C5, C6-C 1C2-C3 and C1-C2-C3-C4 ≈ 0° supported the planar nature of 35DBBS aromatic ring. The theoretically calculated geometrical parameters using B3LYP/6-311++G(d,p) gaseous and water phases are more precise with experimental values than all other functional. The information regarding geometrical parameters of 35DBBS might be promising to reduce the chemical engineering problems and selection of structural correlation. 3.2. Molecular docking Semicarbazide is a urea derivative, which occurs in some food items of animal origin. It is a constituent of nitrofurans, belongs to widely used veterinary drugs and a constituent of azodicarbonamide, utilized as a flour treatment agent. Semicarbazides are the precursor of semicarbazone, tent to combat against the most common bacteria; it's also used in the detection of mobile phase in TLC. Semicarbazide products having anti-infective activities are reported earlier [38,39]. In this docking study, BIOVIA discovery studio 2017 version software [40–43] was used to predict the binding interactions of 35DBBS. High resolution crystal structure of anti-infective proteins was downloaded from the RSCB protein data bank (PDB ID: 4KP7). This protein contains two chains (A and B) and active site cavity was present in A chain, therefore, the A chain chosen as target for docking. The docked ligand forms a stable complex with receptor and shown a binding affinity value of −28.368 Kcal/mol (CDOCKER Energy). The ligand binding in to the active site of receptor by H-bond, van der Waals, Alkyl and Pi-alkyl are depicted in Fig. 3. From the docking result, amino acid Asp231 forms strong H – bond (2.1 Å-bond length) with NH2 group of the ligand. Moreover, the two Br atoms in the ligand form Alkyl interaction with

Ile89 and Lys 301, respectively. Additionally, the benzene (hydrophobic group) forms pi-alkyl interaction with Ile302. Addition to the H-bond, Alky and pi-alky interactions, van der Waals interactions also contributed in strong binding affinity of the semicarbazide at active site. Further, PASS (Prediction of Activity Spectra) [44] online tool which assumes several types of activities on the basis of the structure of a compound. PASS analysis of the title compound is given supporting information in Table S1. Anti-infective activity with probability to be active (Pa) value of 0.882 and the crystal structure of anti-infective proteins was obtained from protein data bank website with PDB ID: 4KP7. The stereo chemical quality of the modeled 4KP7 protein structure has been verified using PROCHECK suite. Ramachandran plot results revealed that, the calculated phi-psi torsion angles for all residues in the structure showed that the majority of the amino acid residues were in the most favoured or core, regions (red color) with a percentage of 91.9% (over 90% represent the ideal value), 7.6% of residues were in additional allowed regions (yellow color) and 0.3% and were occurred in generously allowed regions (light yellow color) Fig. 4. In contrast, very low percentages (0.3%) of residues were found to locate the disallowed regions (white color) probably due to large distance from the enzyme's active site. The G-factors, which provide information about the quality of dihedral, overall bond angles of residues were also found all above the unusual values [45]. Additionally, the main chain parameters plot Fig. 5 was also generated to compare the modeled structure with standard structures at same condition. The plot of the six properties shown in Fig. 5 the measured parameters were all inside the dark band in each graph and in indicative of the present models' correlation within the limits of reliable structures. The results of Ramachandran and main-chain parameters plots validated that, 4KP7 was reasonably good in geometry and stereochemistry and are appropriate for the ligandprotein docking studies of the title compound. 3.3. MEP, ALIE surfaces, Fukui functions and noncovalent interactions In order to understand the local reactive properties of title molecule in detail in this work we have calculated MEP descriptor and mapped it to the electron density surface for the purpose of clear visualization. The importance of MEP lies in the fact that this quantity can be used as an effective tool for the elucidation of biochemistry related phenomena [46]. This quantity is directly connected to the electronic density, which designates this descriptor to be the fundamental one. To the

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Table 1 Optimized geometrical parameters of 35DBBS obtained by gaseous and aqueous phases. Bond length

Gaseous phase

Aqueous phase

Experi.

B3LYP/6-31

B3LYP/ 6-311++ G(d,p)

B3LYP/66-311++ G(d,p) Water

B3LYP/6-311++ G(d,p) Ethanol

B3LYP/6-311++ G(d,p) Aceto nitrile

C(1)-C(2) C(1)-C(6) C(1)-C(10) C(2)-C(3) C(2)-H(7) C(3)-C(4) C(3)-Br(12) C(4)-C(5) C(4)-H(8) C(5)-C(6) C(5)-Br(13) C(6)-H(9) C(10)-N(14) C(10)-H(11) N(14)-N(15) N(15)-C(17) N(15)-H(16) C(17)-N(18) C(17)-O(21) N(18)-H(19) N(18)-H(20)

1.378 1.398 1.462 1.387 1.081 1.396 1.928 1.381 1.081 1.391 1.923 1.084 1.294 1.087 1.361 1.381 1.016 1.360 1.238 1.007 1.005

1.381 1.396 1.462 1.385 1.078 1.396 1.929 1.376 1.078 1.390 1.925 1.080 1.295 1.091 1.364 1.378 1.014 1.359 1.237 1.004 1.002

1.386 1.386 1.461 1.376 1.068 1.379 1.925 1.374 1.068 1.386 1.924 1.070 1.261 1.077 1.374 1.374 1.001 1.341 1.228 0.995 0.996

1.384 1.386 1.453 1.376 1.068 1.379 1.925 1.376 1.068 1.386 1.924 1.070 1.261 1.077 1.374 1.375 1.001 1.341 1.228 0.995 0.996

1.385 1.398 1.456 1.385 1.078 1.396 1.926 1.374 1.077 1.390 1.924 1.080 1.294 1.089 1.369 1.373 1.013 1.353 1.239 1.005 1.003

1.38 1.38 1.45 1.38 0.98 1.38 1.90 1.37 0.98 1.39 1.90 0.99 1.25 0.96 1.37 1.36 0.98 1.33 1.22 0.96 0.96

Bond angle C(2)-C(1)-C(6) C(2)-C(1)-C(10) C(6)-C(1)-C(10) C(1)-C(2)-C(3) C(1)-C(2)-H(7) C(3)-C(2)-H(7) C(2)-C(3)-C(4) C(2)-C(3)-Br(12) C(4)-C(3)-Br(12) C(3)-C(4)-C(5) C(3)-C(4)-H(8) C(5)-C(4)-H(8) C(4)-C(5)-C(6) C(4)-C(5)-Br(13) C(6)-C(5)-Br(13) C(1)-C(6)-C(5) C(1)-C(6)-H(9) C(5)-C(6)-H(9) C(1)-C(10)-N(14) C(1)-C(10)-H(11) H(11)-C(10)-N(14) C(10)-N(14)-N(15) N(14)-N(15)-C(17) N(14)-N(15)-H(16) H(16)-N(15)-C(17) N(15)-C(17)-N(18) N(15)-C(17)-O(21) N(18)-C(17)-O(21) C(17)-N(18)-H(19) C(17)-N(18)-H(20) H(19)-N(18)-H(20)

(°) 119.18 121.87 118.94 119.33 119.74 120.93 122.36 119.05 118.60 118.56 121.24 121.27 121.06 118.92 119.02 119.58 120.38 120.04 120.40 118.87 121.25 119.61 122.32 121.84 117.98 118.42 119.55 124.41 120.74 118.16 121.10

(°) 119.31 121.85 118.84 119.40 119.60 121.01 121.64 119.34 118.65 119.12 121.01 120.50 120.42 119.01 119.30 119.66 120.27 120.08 121.99 118.21 121.13 119.62 121.94 122.26 117.95 117.07 119.38 124.24 120.87 118.15 120.98

(°) 119.58 121.27 119.15 119.66 119.73 120.61 121.65 119.80 119.20 119.14 120.38 120.49 120.84 119.46 119.70 119.78 120.37 119.85 121.27 117.23 122.51 119.08 120.24 121.13 118.63 115.13 119.10 121.29 124.77 118.71 120.00

(°) 119.58 121.26 119.16 119.66 119.73 120.61 121.34 119.80 119.20 119.14 120.38 120.49 120.84 119.46 119.70 119.79 120.37 119.84 121.28 117.23 122.50 119.08 120.26 121.13 118.61 115.12 119.34 124.78 121.29 118.69 120.02

(°) 119.42 121.87 118.71 119.24 119.64 121.11 122.24 119.28 118.48 119.85 121.13 121.21 121.97 118.82 119.21 119.46 120.13 120.41 121.36 117.09 121.56 119.35 121.14 121.90 117.96 117.73 119.38 124.89 120.88 119.03 120.10

(°) 119.5 – – 120.0 119.2 120.1 121.6 – – 118.9 119.8 119.6 120.2 – – 119.5 119.8 119.4 120.4 – – 118.5 120.4 120.8 118.6 118.2 119.4 122.2 119.6 118.9 –

Dihedral angle C(6)-C(1)-C(2)-C(3) C(6)-C(1)-C(2)-H(7) C(10)-C(1)-C(2)-C(3) C(10)-C(1)-C(2)-H(7) C(2)-C(1)-C(6)-C(5) C(2)-C(1)-C(6)-H(9) C(10)-C(1)-C(6)-C(5) C(10)-C(1)-C(6)-H(9) C(2)-C(1)-C(10)-N(14) C(2)-C(1)-C(10)-H(11) C(6)-C(1)-C(10)-N(14) C(6)-C(1)-C(10)-H(11) C(1)-C(2)-C(3)-C(4) C(1)-C(2)-C(3)-Br(12) H(7)-C(2)-C(3)-C(4)

(°) 0.00 −180.00 −180.00 0.00 0.00 180.00 180.00 0.00 0.01 −180.00 180.01 0.01 0.00 180.00 −180.00

(°) 0.00 −180.00 −180.00 0.00 0.00 180.00 180.00 0.00 0.01 −180.00 180.01 0.01 0.00 180.00 −180.00

0.00 −180.00 180.00 0.00 0.00 180.00 −180.00 0.00 180.00 0.00 0.00 −180.00 0.00 −180.00 180.00

(°) 0.00 −180.00 180.00 0.00 0.00 180.00 −180.00 0.00 180.00 0.00 0.00 −180.00 0.00 −180.00 180.00

(°) 0.00 −180.00 −180.00 0.00 0.00 180.00 180.00 0.00 −180.00 0.01 −0.01 180.01 0.00 180.00 −180.00

(°) – – – – – – – – – – – – – –

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M. Muthukkumar et al. / Journal of Molecular Liquids 272 (2018) 481–495 Table 1 (continued) Bond length

H(7)-C(2)-C(3)-Br(12) C(2)-C(3)-C(4)-C(5) C(2)-C(3)-C(4)-H(8) Br(12)-C(3)-C(4)-C(5) Br(12)-C(3)-C(4)-H(8) C(3)-C(4)-C(5)-C(6) C(3)-C(4)-C(5)-Br(13) H(8)-C(4)-C(5)-C(6) H(8)-C(4)-C(5)-Br(13) C(4)-C(5)-C(6)-C(1) C(4)-C(5)-C(6)-H(9) Br(13)-C(5)-C(6)-C(1) Br(13)-C(5)-C(6)-H(9) C(1)-C(10)-N(14)-N(15) H(11)-C(10)-N(14)-N(15) C(10)-N(14)-N(15)-C(17) C(10)-N(14)-N(15)-H(16) N(14)-N(15)-C(17)-N(18) N(14)-N(15)-C(17)-O(21) H(16)-N(15)-C(17)-N(18) H(16)-N(15)-C(17)-O(21) N(15)-C(17)-N(18)-H(19) N(15)-C(17)-N(18)-H(20) O(21)-C(17)-N(18)-H(19) O(21)-C(17)-N(18)-H(20)

Gaseous phase

Aqueous phase

Experi.

B3LYP/6-31

B3LYP/ 6-311++ G(d,p)

B3LYP/66-311++ G(d,p) Water

B3LYP/6-311++ G(d,p) Ethanol

B3LYP/6-311++ G(d,p) Aceto nitrile

0.00 0.00 180.00 −180.00 0.00 0.00 −179.99 180.00 0.00 0.00 180.00 −180.00 0.00 −180.00 0.00 0.00 −180.00 0.00 −180.00 180.00 0.00 0.00 −180.00 180.00 0.00

0.00 0.00 180.0001 −180.00 0.00 0.00 −179.99 180.00 0.00 0.00 180.00 −180.00 0.00 −180.00 0.00 0.00 180.01 0.00 180.00 180.01 0.01 0.00 180.00 180.01 0.00

0.00 0.00 180 180 0.00 0.00 −180 −180.00 0.00 0.00 180.00 180.00 0.00 180.00 0.00 0.00 180.00 0.00 −180.00 180.00 0.00 0.00 −180.00 180.00 0.00

0.00 0.00 180 180 0.00 0.00 −180 −180.00 0.00 0.00 180.00 180.00 0.00 180.00 0.00 0.00 180.00 0.00 −180.00 180.00 0.00 0.00 −180.00 180.00 0.00

0.00 0.00 180.00 −180.00 0.00 0.00 −180.00 180.00 0.00 0.00 180.00 −180.00 0.00 −180.01 0.00 0.00 180.00 0.00 180.00 180.00 0.00 0.00 180.00 −180.00 0.00

– – – – – – – – – – – – – – – – – – – – – – – – –

486


Fig. 3. The docked ligand interacting with the amino acids of complement factor.

established the correlation between MEP and different aspects of chemical reactions, this tool has been extensively applied for the analysis and prediction of reactivity of various molecular structures. For example, Sjoberg and Politzer [47] demonstrated how MEP can be used for the interpretation and prediction of nucleophilic processes. Politzer et al. [48,49] used MEP in order to address the noncovalent interactions in biological systems. MEP descriptor is vastly used for determination of molecular areas which are sensitive towards electrophilic and nucleophilic attacks [49–52]. While MEP is suitable for the treatment of noncovalent interactions, ALIE descriptor has better performance when it comes to the identification of molecular prone to electrophilic attacks. Reactions during which new bonds are formed are frequently not guided by electrostatic interactions; meaning that these cases are better understood using the ALIE quantum-molecular descriptor. However, identification of molecular areas sensitive towards electrophilic attacks might be better performed by utilization of ALIE descriptor, which is interpreted as energy required to remove an electron from certain points of molecule

Fig. 4. Ramachandran plots of (35DBBS) 4KP7 protein. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)

[52–58]. Same as in the case of MEP descriptor, ALIE is also visualized by mapping of its values to the electron density surface. Taking into account the importance of both descriptors, in this work we have used both of them in order to identify reactive sites of 35DBBS (Fig. 6). MEP surface recognizes only the near vicinity of oxygen atom to be sensitive towards electrophilic attacks. This molecular area is characterized by the lowest MEP values (≈42 kcal/mol). The highest MEP values have been calculated for all hydrogen atoms, with the corresponding values of about ≈46 kcal/mol. Aside of oxygen atom, ALIE surface identifies near vicinities of bromine atoms to be also sensitive towards electrophilic attacks. These reactive sites are characterized by the lowest ALIE values of ≈207 kcal/mol. Local reactivity of 35DBBS molecule have also been identified by employing the concept of Fukui functions. According to this descriptor changes of electron density are tracked as a consequence of change of overall charge. In this way molecular areas where electron density increases or decreases can be detected. In Jaguar program Fukui functions can be calculated in finite difference approximation according to the following equations: fþ ¼

  ρNþδ ðrÞ−ρN ðrÞ δ

ð1Þ

f− ¼

 N−δ  ρ ðrÞ−ρ N ðrÞ δ

ð2Þ

where, N denotes number of electrons in reference state of the molecule, and δ denotes fraction of electron which default value is set to be 0.01 [59]. The f+ function is related to the LUMO orbital and therefore measures the reactivity towards the donor species, while f− function on the other side is related to HOMO orbital, measuring the reactivity towards the acceptor species. In these regards, Fukui a function complements the local reactivity picture of obtained by MEP and ALIE quantum-molecular descriptors. The values of Fukui functions are mapped to the electron density and the results are presented in Fig. 7. In Fig. 7 blue-to-purple color in left panel is used for the maximal values of Fukui f + function, and this color identified molecule areas where electron density increased after a charge addition. Red color in right panel of Fig. 7 identified molecule areas where electron density decreased after the removal of charge. According to results presented in left panel of Fig. 7, electron density after charge addition increased in three locations: near vicinity of nitrogen atom N14 , near vicinity of hydrogen atom H8 and near vicinity of bond C10 –H11. These molecule sites act as electrophiles, after addition of charge. Results in right


487

Fig. 5. Ramachandran plot quality assessment generated by PROCHECK.

panel of Fig. 7 indicated that, electron density after charge removal decreased also in three locations: near vicinity of bromine atoms and near vicinity of carbon atom C1, thus these molecule sites have nucleophilic nature after charge removal. Finally the calculated results clearly evidenced that; 35DBBS is slightly high susceptible to electrophilic attack than nucleophilic attack and radical attack. These results highlighted 35DBBS as efficient biological active molecule. 3.4. Sensitivity towards autoxidation and water Autoxidation is one of the most important industrial mechanisms according to which organic molecules are oxidizing in presence of oxygen. This type of sensitivity of molecules is particularly important for the development of advance oxidation processes [ 8,49,50,60–62]. DFT

calculations can be used for prediction of sensitivity towards this mechanism by calculations of H-BDE parameter, which is of great importance taking into account how difficult and expensive is to experimentally measure bond dissociation energies [10,61]. Sensitivity of organic molecule towards autoxidation is reflected through H-BDE values in a range of 70–85 kcal/mol [63], while H-BDE values in a range between 85 and 90 kcal/mol might also indicate sensitivity towards this mechanism, however these values should be taken with caution as autoxidation might be prevented by some other mechanism [64]. H-BDE values of 35DBBS molecule have been indicated in Fig. 8. There are three hydrogen atoms with relatively significant interactions with water molecules, according to calculated RDFs (Fig. 9). These three hydrogen atoms are H16 , H 20 and H 21. Although their maximal g(r) values are located at relatively short distances, maximal g

488


Fig. 6. MEP and ALIE surfaces of 35DBBS molecule.

(r) values are the lowest of all values calculated in this work. In the close vicinity of these atoms there is also carbon atom C17 which has pronounced interactions with water molecules, according to the maximal g(r) value and sharp RDF profile. Its maximal g(r) value is, however, located at high distance of almost 4 Å. According to RDFs, bromine atoms also have relatively important interactions with water molecules; however, their maximal g(r) values are located at distances of around 3.5 Å. 3.5. Frontier molecular orbitals (FMO) Frontier molecular orbitals (FMO) of highest occupied molecular orbitals (HOMO) as well as lowest unoccupied molecular orbitals (LUMO) played a vital role in calculating the electronic and optical properties as well as chemical reactions. The EHOMO-ELUMO energy gap reveals molecular polarizability, chemical softness, chemical hardness, kinetic stability and the reactivity of molecules [ 64–67 ]. The molecule possesses lower energy gap between the FMO shows higher reactivity, low kinetic stability and greater intermolecular actions, thus the molecule is said to be soft molecule [68–70]. The molecule possesses greater energy gap between the FMOs is said to be hard molecule which has higher thermal and kinetic stabilities as stated in softness-hardness rule. The EHOMO -ELUMO energy gap for 35DBBS has been computed in various functional levels and is listed in Table 2 which indicated the molecule as highly reactive (supporting information Fig. S1). The lesser value of energy gap revealed the

occurrence of the intra-molecular charge transfer in the 35DBBS, which might increase the NLO activity of the molecule. 3.6. The global chemical reactivity descriptors (GCRD) The GCRD associated with DFT is a significant analytical tool which helps in understanding the relationship among the structure, stability and reactivity of molecules. Several GCRD parameters viz., hardness (η), softness (σ), chemical potential (μ), electronegativity (χ) and electrophilicity (ω) were calculated for 35DBBS by taking the EHOMO as ionization energy (I) and ELUMO as electron affinity (A) (Table 2). Koopmans theorem could also be used to assume the ionization energy as well as electron affinity of chemical species. This theorem describes that ionization energy and electron affinity values of molecules represent to the negative of its EHOMO and ELUMO values. According to Koopman's theorem [71], hardness and electronegativity of a moleculecan be calculated by following formula.

χ ¼ −μ ¼

η¼

I −A 2

IþA 2

ð3Þ

ð4Þ

Fig. 7. Fukui functions of 35DBBS molecule, with corresponding maximal and minimal values. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)


489

3.7. Natural bond orbital (NBO)

Fig. 8. H-BDE values for 35DBBS molecule.

χ¼

η¼

EHOMO þ ELUMO 2 EHOMO −ELUMO 2

ð5Þ

ð6Þ

Softness (σ) which is a magnitude of the polarizability of chemical species is de fined as the inverse of multiplicity hardness (σ = 1/η). Electrophilicity (ω) and nucleophilicity are the two significant chemical reactivity indices. Parr [66] derived the following formula to calculate the electrophilicity index associated with electronegativity and hardness of molecules [66,67]. Further, he stated the nucleophilicity (ε) as the multiplicative inverse of electrophilicity (ω = 1/ε)

ω¼

χ2 2η

ð7Þ

The hardness and softness values of molecule are 2.2 eV and 0.45 eV, respectively. The molecule with larger value of hardness is low toxic and vice versa. The calculated GCRD parameters viz., chemical potential, electronegativity and electrophilicity suggested 35DBBS as highly reactive strong molecule.

The study of inter-molecular bonding, interaction among bonds and also the evaluation of charge transfer or conjugative interactions occurring in molecular systems could be effectively analyzed by NBO analysis. The NBO calculations [72] were performed using the NBO 3.1 program as implemented in the Gaussian 09 W package in order to determine the various second order interactions between the filled orbitals and vacant orbitals in various subs system, which is an assessment of the intermolecular delocalization or hyperconjugation. NBO analysis gives the most accurate feasible ‘natural Lewis structure’ of j, because all orbital details are mathematically selected to include the highest promising percentage of the electron density (ED). The significance of NBO method is that, it validates the interactions in both filled and virtual orbital spaces, thus developing the analysis of inter/intra-molecular interactions. To evaluate the donor-acceptor interactions based on NBO, the second order Fock matrix was considered [69,70]. The interactions resulted the transfer of electrons from the localized NBO of the idealized Lewis structure to the non-Lewis orbital. For every donor (i) and acceptor (j) the stabilization energy (E (2)) coupled with the delocalization i → j is determined as Eð2Þ ¼ −q i

2 F i; j ε j −ε i



ð8Þ

where qi is the orbital occupancy of donor, εI and εj are diagnol elements and F(i,j) is the offdiagonal NBO Fock matrix element. In NBO analysis greater E(2) value exhibits the exhaustive interaction between donors and acceptors and leads to greater conjugation of the whole system. NBO analysis has been carried out on the molecule at the DFT/B3LYP/6-311++G(d,p) level with a view to determine the inter molecular, rehybridization and delocalization of electron density within the molecule (Table 3). The intra-molecular hyper-conjugative interactions occurred in 35DBBS molecule orbital are as follows: σC 1-C2 → σ*C 3-Br12 as 6.87 KJ/mol, πC1-C6 → σ*C5-Br13 as 6.64 KJ/mol, σC 1 -C10 → σ*N14-N15 as 5.89 KJ/mol, πC10-N14 → π*C1 -C6 as 13.12 KJ/mol LP Br 12 → π*C2 -C3 as 11.52 KJ/mol, LP Br 13 → π*C 4-C5 as 11.47 KJ/mol, LP N15 → π*C10N 14 as 42.02 KJ/mol, LP N 18 → σ*C17 -N18 as 119.07 KJ/mol, LP O 21 → σ*N15-C17 as 31.18 KJ/mol and LP O21 → σ*C17-N18 as 27.19 KJ/mol. In the present study, the observed highest stabilization energy (E 2) for 35DBBS molecule revealed the strongest interaction between electron donor and acceptor. In common, electron donating group substituted derivatives exhibited better antimicrobial properties than electron withdrawing compounds [51–54]. The NBO results supported the better antimicrobial property of 35DBBS. 3.8. Vibrational spectral analysis 35DBBS compound consisted twenty one atoms and possesses 57 normal modes of vibrations as shown in Table 4. The comparison between the observed FT-IR and FT-Raman spectra frequencies of 35DBBS with calculated IR and Raman spectral wave numbers has been done (Figs.10 and 11). The complete description of experimental FT-IR and FT-Raman spectra is listed in Table 4 along with comprehensive assignment as stipulated by TED. The scaled vibrational frequencies were well correlated with experimental vibrational frequencies. Some of the bands in theoretically calculated FT-IR are missing in experimental FT-IR due to the coexistence of broader and larger bands. The observed and calculated vibrational assignments frequencies for various functional groups are conversed below.

Fig. 9. RDFs of atoms of 35DBBS molecule with signi ficant interactions with water molecule.

3.8.1. NH2 and NH vibrations Generally, symmetric and asymmetric stretching vibration frequencies are appeared at 3400–3500 cm −1 [73]. In the present study, observed NH2 asymmetric and symmetric stretching vibration of 35DBBS

490


Table 2 Physico-chemical parameters of 35DBBS. Functional/set Gaseous phases Aqueous phases

B3LYP/6-31 B3LYP/6-311++G(d,p) B3LYP/6-31 B3LYP/6-311++G(d,p)

EHOMO

IE

E LUMO

EA

ΔE

χ

η (eV)

σ (eV)

ω

ὲ

Energy

−6.737 −6.846 −6.536 −6.563

6.737 6.846 6.536 6.563

−2.266 −2.414 −2.036 −2.055

2.266 2.414 2.036 2.055

4.471 4.433 4.499 4.509

4.502 4.630 4.286 4.309

2.236 2.216 2.250 2.254

0.447 0.451 0.445 0.444

4.5324 4.8360 4.0830 4.1182

0.221 0.207 0.245 0.243

−5696.71 −5696.72 −5696.71 −5696.72

HOMO -Highest Occupied Molecular Orbital, LUMO -Lowest Unoccupied Molecular Orbital, IE-Ionization, EA- Electron Affinity, Softness (σ), Hardness (η), Electrophilicity index (ω), Electronegativity (χ), Electrophilicity index (ὲ).

are appeared at 3510 cm −1 (FT-IR), 3498 cm−1 (FT-Raman) and 3466 cm−1 (FT-IR). The calculated asymmetric NH 2 vibrational frequencies are found at 3511 cm−1 and symmetric NH 2 at 3470 cm−1 (Mode No.1 and 2). In addition, observed NH stretching vibrations of 35DBBS are appeared at 3378 cm−1 in FT-IR and 3382 cm−1 in FT-Raman, which is agreed with computed vibrational wave number 3386 cm−1 (mode no 3). Usually, NH in-plane bending vibrations were occurred in the region 1500–1550 cm−1 [19–22,74]. In the present study, the observed NH in-plane bending vibrations of 35DBBS are assigned at 1566 cm−1 in FT-IR and 1552 cm−1 in FT-Raman. The NH out-of-plane bending vibrations are appeared at 1251, 1095 cm−1 in FT-IR and FTRaman at 1081 cm −1. The computed vibrations frequencies are appeared at 1574, 1557 cm−1 and out-of plane bending at 1253, 1092 cm−1. The observed NH 2 wagging vibrational frequencies are appeared at which appeared 345 cm−1, which is agreed with is calculated frequencies at 344 cm −1. The theoretically calculated NH vibrational frequencies (asymmetric stretching, symmetric stretching, in-plane bending, out-of-plane bending and wagging) are well agreed with experimental values, which are showed in Table 4.

3.8.2. C\\H vibrations Generally, aromatic C\\H stretching vibrations are appeared in the range 3000–3100 cm−1, which are the characteristic region for the ready identification of C\\H stretching vibrations [72–75]. Observed C\\H stretching vibrations of 35DBBS are assigned at 3092, 2941 cm−1 in FT-IR and FT-Raman at 3094, 3069 cm−1. The C\\H inplane bending vibration modes are usually appeared in the region 1000–1300 cm−1. The observed C\\H in-plane bending vibrations are appeared at 1251, 1210 cm−1 in FT-IR and FT-Raman at 1285, 1114, 1081 cm−1 . The theoretically calculated in-plane bending vibration modes are found at 1288–1081 cm −1 mode nos. 18–21, 23 which are excellently correlated with experimental values. The C\\H out-ofplane bending frequencies of aromatic benzene and its derivatives are predictable to occur in between 750 and 1000 cm−1 [75–77]. The calculated C\\H out-of-plane bending frequencies are appeared at 973, 956, 948, 906, 859 and 710 cm −1 (mode nos. 25, 26, 27, 28, 30 and 31) which are well agreed with observed FT-IR and FT-Raman bands at 980, 948, 904, 712 and 950, 855 cm −1.

3.8.3. C\\C vibrations In general, the carbon-carbon stretching vibrations are appeared in the region 1100–1600 cm−1, which is not appreciably influenced with the nature of substituent groups [73– 75]. In common, the modes are changeable intensity and experimental at 1590–1625, 1575– 1590, 1470– 1540, 1430–1465 and 1280–1380 cm −1 from the frequencies range given varsanyi for the five modes in the region. The observed C\\C stretching vibration frequencies of 35DBBS have appeared at 1566, 1410, 1328, 1210 cm−1 in FT-IR and 1552, 1451, 1325 cm −1 in FT-Raman, which are well correlated with calculated vibration bands at 1574, 1557, 1520, 1455, 1412, 1331 and 1211 cm−1 using B3LYP/6311++G(d,p) functional (mode nos. 10–14, 17 and 20). The bands at 980, 948, 445 cm−1 in FT-IR and 512, 210 cm−1 in FT-Raman are presented C-C-C deformation of phenyl ring, which is well correlated with calculated vibration frequencies.

3.8.4. C\\N vibrations The C_N and C\\N stretching frequency is a very tough task since, it falls in a composite region of the vibrational spectra, i.e., mixing of several bands are possible in this region assigned CN stretching absorption in the region 1080–1360 cm−1 for the aromatic compound [19–22]. In the present work, the observed C10_N14 stretching vibration frequencies are appeared at 1654 cm−1 in FT-IR and FT-Raman at 1662 cm−1, which are well correlated with theoretically calculated vibration frequencies 1660 cm−1 (mode no.8). Additionally, the observed C\\N stretching vibration frequencies are appeared at 1365 cm−1 in FT-IR and FT-Raman at 1385 cm−1, which are also agreed with computed vibration frequencies 1389, 1371 cm−1 (mode nos.15,16). The observed in-plane and out-of-plane bending vibrations are appeared at 322 and 255 cm−1 in FT-Raman, respectively.

3.8.5. C\\Br vibrations Generally, vibrations of aromatic halogen (Cl, Br, F …etc.,) compounds are occur in the region 650–395 cm−1 [20,53]. In the present study, the observed vibrational frequencies are appeared at 545 cm−1 in FT-IR and 540 cm−1 in FT-Raman. The calculated vibrational frequencies (547 cm−1) are well correlated with experimental frequencies. In addition, the observed in-plane and out-of-plane bending vibrations are appeared at 345, 310 cm−1 and 255, 210 cm−1 , respectively.

3.8.6. C_O, N\\C\\N, C\\C\\N, C\\N\\N, H\\N\\C\\O and O\\C\\N vibrations The observed C_O stretching vibration of 35DBBS are appeared at 1654 in FT-IR and 1662 cm−1 in FT-Raman. NCN bending bands assigned at 881 cm−1 and 575 cm −1 in FT-IR and C\\C\\N bands appeared at 670 cm−1 in FT-IR and 674 cm−1 in FT-Raman, which are well agreed with experimental values. The H\\N\\C\\O bending vibrations are appeared at 510 cm−1 in FT-IR and, 512 cm −1 in FT-Raman. The C-N-N bending vibration is assigned at 670 cm−1 in FT-IR and OC-N bending vibrations are assigned at 891 cm−1 in FT-Raman. All theoretically calculated vibrations are well agreed with observed values.

3.9. NMR spectra analysis NMR spectral analysis provided a detailed account establishing the correct assignment of the protons and carbons [78–80]. DFT theoretical calculations are a valuable tool to support the assignment of individual protons and carbons in the structure of complex natural products [78]. The observed 13 C and 1H NMR chemical shifts were presented in supporting information Figs. S2 and S3. The theoretically calculated chemical shifts values (13C and 1H) using gauge invariant atomic orbital (GIAO) B3LYP/6-311++G(2d,p) functional are compared with experimental NMR spectral data. The observed and calculated values for carbon and proton NMR of 35DBBS are listed supporting information in Table S2. Generally, aromatic compound of chemical shifts isotropic carbons are presented in the range of 100–160 ppm [18–22]. In the present study, the experimental 13C chemical shift of 35DBBS are appeared at C1 (138.15), C2 (122.15), C3 (141.58), C4 (134.25), C5 (138.65), C 6 (128.65), C10 (138.54) and C 17 (156.85) which is well correlated with theoretical chemical shifts.

491

M. Muthukkumar et al. / Journal of Molecular Liquids 272 (2018) 481–495 Table 3 Second order perturbation theory analysis of Fock Matrix in NBO basis corresponding to the intra-molecular bonds of 35DBBS. Donor NBO (i)

Occupancy(i)

Acceptor NBO (j)

Occupancy (j)

E(2) kcal/mol

E(j)-E(i) a.u.

F(i,j) a.u.

σC1-C2

1.967

πC1-C6

1.968

σC1-C10

1.971

πC2-C3

1.980

σC2-H7

1.979

σC3-C4

1.974

σC3-Br12

1.980

πC4-C5

1.974

σC4-H8

1.977

σC5-C6

1.980

σC5-Br13

1.981

σC6-H9

1.980

σC10-H11

1.989

πC10-N14

1.987

σN14-N15

1.987

σN15-H16

1.991

σN15-C17

1.990

π*C1-C6 σ*C1-C10 π*C2-C3 σ*C3-Br12 σ*C6-H9 σ*C10-H11 σ*C1-C2 σ*C1-C10 σ*C2-H7 σ*C5-C6 σ*C5-Br13 σ*C6-H9 π*C10-N14 σ*C1-C2 π*C1-C6 π*C2-C3 σ*C5-C6 σ*C10-H11 σ*C10-N14 σ*N14-N15 σ*C1-C2 σ*C1-C10 σ*C2-H7 σ*C3-C4 σ*C4-H8 π*C1-C6 π* C2-C3 σ*C3-C4 σ*C3-Br12 π*C2-C3 σ*C2-H7 π*C4-C5 σ*C4-H8 σ*C5-Br13 σ*C2-H7 π*C4-C5 σ*C4-H8 σ*C3-C4 σ*C3-Br12 σ*C4-H8 π*C5-C6 σ*C6-H9 π*C2-C3 σ*C3-C4 σ*C3-Br12 π*C4-C5 σ*C5-C6 σ*C5-Br13 π*C1-C6 σ*C1-C10 π*C4-C5 σ*C4-H8 σ*C6-H9 π*C1-C6 σ*C3-C4 σ*C4-H8 σ*C6-H9 σ*C1-C6 π*C4-C5 σ*C5-C6 σ*C5-Br13 σ*C1-C2 σ*C1-C10 π*C1-C6 π*C1-C6 σ*C1-C10 σ*C10-H11 σ*N15-C17 σ*C1-C10 π*C10-N14 π*C17-O21 σ*C17-N18 π*C17-O21 π*C10-N14

0.022 0.022 0.023 0.027 0.013 0.022 0.026 0.022 0.013 0.023 0.026 0.013 0.008 0.026 0.022 0.023 0.023 0.022 0.008 0.016 0.026 0.022 0.013 0.027 0.014 0.022 0.023 0.027 0.027 0.023 0.013 0.026 0.014 0.026 0.013 0.026 0.014 0.027 0.027 0.014 0.023 0.013 0.023 0.027 0.027 0.026 0.023 0.026 0.022 0.022 0.026 0.014 0.013 0.022 0.027 0.014 0.013 0.022 0.026 0.023 0.026 0.026 0.022 0.022 0.022 0.022 0.022 0.061 0.022 0.008 0.009 0.047 0.009 0.008

5.21 3.61 5.47 6.87 2.68 1.69 5.11 3.16 2.53 5.44 6.64 1.86 1.86 3.89 3.29 2.62 2.89 0.66 3.68 5.89 5.03 3.57 2.75 4.59 2.48 5.46 2.23 5.85 0.57 4.58 2.64 5.67 2.66 6.19 1.06 4.48 1.13 5.65 5.99 2.73 4.67 2.71 5.52 1.98 0.58 2.06 5.61 0.59 5.12 3.55 4.67 2.55 2.62 4.57 4.51 1.12 1.07 1.44 5.59 2.05 0.51 5.06 0.64 1.79 13.12 3.09 0.69 3.14 3.35 0.51 1.55 3.48 0.65 3.28

1.72 1.63 1.74 1.17 1.58 1.53 1.72 1.63 1.61 1.74 1.18 1.59 1.76 1.69 1.69 1.71 1.7 1.5 1.72 1.53 1.77 1.68 1.66 1.77 1.65 1.5 1.53 1.5 0.96 1.79 1.64 1.77 1.64 1.22 1.47 1.6 1.46 1.77 1.22 1.64 1.78 1.63 1.53 1.51 0.96 1.51 1.52 0.96 1.77 1.68 1.78 1.65 1.64 1.59 1.56 1.47 1.46 1.51 1.52 1.52 0.96 1.53 1.44 1.98 0.61 1.89 1.79 1.83 1.83 1.95 1.95 1.59 1.71 1.88

0.085 0.069 0.049 0.08 0.058 0.046 0.084 0.064 0.057 0.087 0.079 0.049 0.051 0.072 0.067 0.06 0.063 0.028 0.071 0.085 0.084 0.069 0.06 0.081 0.057 0.081 0.052 0.084 0.021 0.081 0.059 0.089 0.059 0.077 0.035 0.076 0.034 0.089 0.076 0.06 0.081 0.059 0.082 0.049 0.021 0.05 0.082 0.021 0.084 0.069 0.081 0.058 0.059 0.076 0.076 0.034 0.035 0.042 0.082 0.05 0.2 0.079 0.027 0.053 0.087 0.068 0.082 0.068 0.07 0.028 0.049 0.067 0.03 0.07 (continued on next page)

492


Table 3 (continued) Donor NBO (i)

Occupancy(i)

σC17-N18

1.994

πC17-O21

1.993

σN18-H19

1.991

σN18-H20

1.991

LP Br12

1.995

LP Br13

1.995

LP N14

1.946

LP N15 LP N18 LP O21

1.778 1.816 1.980

Acceptor NBO (j)

Occupancy (j)

E(2) kcal/mol

E(j)-E(i) a.u.

F(i,j) a.u.

π*C17-O21 σ*N18-H20 σ*N15-H16 π*C17-O21 σ*N14-N15 σ*N15-C17 σ*C17-N18 σ*N18-H19 σ*N15-C17 π*C17-O21 σ*N15-C17 π*C17-O21 π*C2-C3 σ*C3-C4 π*C4-C5 σ*C5-C6 σ*C1-C6 σ*C1-C10 σ*C10-H11 σ*N15-H16 σ*N15-C17 σ*N18-H19 π*C10-N14 σ*C17-N18 σ*N15-C17 σ*C17-N18

0.009 0.004 0.020 0.009 0.016 0.061 0.047 0.006 0.061 0.009 0.061 0.009 0.023 0.027 0.026 0.023 0.022 0.022 0.022 0.020 0.061 0.006 0.008 0.047 0.061 0.047

0.58 2.17 2.12 1.52 2.62 1.09 1.99 1.44 0.83 5.38 5.42 0.56 11.52 4.26 11.47 4.07 0.53 2.18 11.16 10.03 0.79 0.66 42.02 119.07 31.18 27.19

1.88 1.74 1.73 1.92 1.91 1.92 1.99 1.97 1.52 1.71 1.51 1.7 0.55 1.2 0.55 1.22 1.2 1.29 1.19 1.22 1.22 1.27 0.56 0.36 1.04 1.11

0.03 0.055 0.055 0.048 0.063 0.041 0.057 0.048 0.032 0.086 0.082 0.027 0.077 0.064 0.077 0.063 0.023 0.048 0.104 0.1 0.028 0.026 0.139 0.214 0.162 0.157


493

Table 4 Vibrational assignments of experimental frequencies of 35DBBS along with calculated frequencies by B3LYP/6-311G++(d,p) functional. S. No.

Observed frequency (cm−1)

Calculated frequency (cm−1) with B3LYP/6-311G++(d,p) force field

PED (%) among type of internal coordinates c

Infrared Raman Unscaled Scaled IRa Ramanb A i Ii 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47

3510 3466 3378 – 3092 – 2941 1654 – 1566 – – – 1410 – 1365 1328 – 1251 1210 – 1095

48 49 50 51 52 53 54 55 56 57

3498 – 3382 3094 – 3069

980 – 948 904 – 881 – 712 – – 670 595 – 575 545 – – 510 445 – – – –

1081 – – 950 – – 891 – 855 – 703 674 – – – – 540 – 512 – – 345 322 310 –

3653 3611 3523 3231 3230 3199 3064 1728 1644 1638 1621 1581 1514 1469 1445 1426 1385 1340 1304 1260 1162 1137 1125 1102 1013 994 987 943 929 913 894 738 737 707 704 623 604 599 570 544 538 528 468 357 334 329 299

3511 3470 3386 3105 3104 3074 2945 1660 1580 1574 1557 1520 1455 1412 1389 1371 1331 1288 1253 1211 1117 1092 1081 1059 973 956 948 906 893 878 859 710 708 679 677 598 581 575 547 523 517 508 449 344 321 316 287

18 6 4 0 0 2 4 6 15 3 0 48 24 25 10 55 12 2 1 4 0 31 5 6 12 54 2 6 5 54 4 26 2 36 2 6 1 1 1 0 12 6 2 1 0 18 6

4 8 20 8 6 2 8 5 9 94 68 25 5 0 9 5 8 0 0 45 22 12 54 4 2 24 6 24 4 2 32 3 26 3 1 0 0 0 2 8 4 1 0 1 2 4 8

– – – – – – – – – –

255 210 – 150 – 110 – – – –

273 221 192 166 149 117 116 55 47 26

262 212 184 159 143 112 111 52 45 25

4 0 0 2 4 0 0 1 0 1

12 8 6 2 8 5 9 1 0 1

1662 – – 1552 – 1451 – 1385 – 1325 1285 – – 1114

asymγNH 2(98) symγNH2 (99) γNH(96) γCH(99) γCH(94) γCH(96) γCH(100) γOC(64), γNC(24) γNC(48) γCC(44), δNH(34) δNH(60), γCC(42) γCC(48) γCC(42) γCC(34) γNC(38) γNC(34) γCC(28) γNN(52), δHCC(21) δHCC(40), βNH(23) δHCC(52), γCC(24) δHCC (68) βNH(65) βHN(45), δHCC(24) δHNC(24) βHCC(46), τCCC(28) βHCC(34) βHCC(49), τCCC(24) βHCC(24) βOCN(28) βNCN(64) βHCC(38) βHCC(31) τHCCC(20) βCCN(37) βCNN(24) βCCN(64) τCCC(42) βNCN(21) γBrC(64) τHNCO(21) τHNCO(14), τCCC(12) τHNCO(18) τHCCC(45), τCCC(08) δBrC(24), ɷNH 2 (15) τHCCC(12), δNC(12) δBrC(34), τHCCC(14) τCCCBr(18), τHCCC (12) βBrC(28), δNC(18) βBrC(24), τCCCC(08) τCCCC(10) τCCCBr(45) Out CCCN(14) Out CCCBr(64) τCNNO(12) τCCCBr(18), τCCCN τCCCBr(21) τCCCC(10)

From the results, have been observed the high electronegative property polarizes of oxygen nitrogen and bromine atoms are affected the electron distribution of adjacent carbon atoms, which is decreased electron density and chemical shift are presented in high ranges (C3, C5, C 10 and C 17 are higher chemical shift comparing other carbons). Aromatic ring protons are highly influenced the most due to the induced ring current of the aromatic π -electrons. The aromatic ring protons are appeared in the range of 6.5–8.5 ppm [79,80]. In the present work, there

Fig. 10. FT-IR spectra of 35DBBS (Calculated and Experimental).

are six hydrogen atoms (ring, NH, NH2 ) present in title compound. The 1H NMR experimental chemical shift values at 7.56, 7.62, 7.21, 6.59, 6.23 and 6.12 ppm with theoretically calculated chemical shift values at 7.55, 7.29, 7.93, 6.80, 6.72 and 6.60 ppm for H 7, H 8, H9 H 11, H 19 and H 20. The theoretically calculated chemical shift values well correlated with experimental values. 3.10. NLO properties NLO is at the forefront of current research due to its importance in providing key functions of frequency shifting, optical modulation, switching, laser, fiber, optical materials logic and optical memory for the emerging technologies in areas such as telecommunications, signal processing and optical inter connections [80–82]. In order to investigate the relationship between molecular structure and NLO, the polarizibilities and hyperpolarizibilities of 3DBBS are calculated using

Fig. 11. FT-Raman spectra of 35DBBS (Calculated and Experimental).

494


B3LYP/6-311G++(d,p). Total static dipole moment (μ), mean polarizibility, anisotropy (α), the polarizability ( Δα) and mean firstorder hyperpolarizibility (β) of 3DBBS are listed in supporting information Table S3. The isotropic polarizability (α) is

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