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. 2020 Jul 21;5(30):18907–18918. doi: 10.1021/acsomega.0c02128

An Experimental and Computational Exploration on the Electronic, Spectroscopic, and Reactivity Properties of Novel Halo-Functionalized Hydrazones

Akbar Ali †,*, Muhammad Khalid ‡,*, Muhammad Abdul Rehman †, Farooq Anwar †, Hafiz Zain-Ul-Aabidin †, Muhammad Nadeem Akhtar §, Muhammad Usman Khan ∥, Ataualpa Albert Carmo Braga ⊥, Mohammed A Assiri #, Muhammad Imran #
PMCID: PMC7408231  PMID: 32775892

Abstract

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Herein, halo-functionalized hydrazone derivatives “2-[(6′-chloroazin-2′-yl)oxy]-N′-(2-fluorobenzylidene) aceto-hydrazone (CPFH), 2-[(6′-chloroazin-2′-yl)oxy]-N′-(2-chlorobenzylidene) aceto-hydrazones (CCPH), 2-[(6′-chloroazin-2′-yl)oxy]-N′-(2-bromobenzylidene) aceto-hydrazones (BCPH)” were synthesized and structurally characterized using FTIR, 1H-NMR, 13C-NMR, and UV–vis spectroscopic techniques. Computational studies using density functional theory (DFT) and time dependent DFT at CAM-B3LYP/6-311G (d,p) level of theory were performed for comparison with spectroscopic data (FT-IR, UV–vis) and for elucidation of the structural parameters, natural bond orbitals (NBOs), natural population analysis, frontier molecular orbital (FMO) analysis and nonlinear optical (NLO) properties of hydrazones derivatives (CPFH, CCPH, and BCPH). Consequently, an excellent complement between the experimental data and the DFT-based results was achieved. The NBO analysis confirmed that the presence of hyper conjugative interactions was pivotal cause for stability of the investigated compounds. The energy gaps in CPFH, CCPH, and BCPH were found as 7.278, 7.241, and 7.229 eV, respectively. Furthermore, global reactivity descriptors were calculated using the FMO energies in which global hardness revealed that CPFH was more stable and less reactive as compared to BCPH and CCPH. NLO findings disclosed that CPFH, CCPH, and BCPH have superior properties as compared to the prototype standard compound, which unveiled their potential applications for optoelectronic technology.

Introduction

In the post-modern era, pharmacological advancement has gone beyond the scope of conventional manufacturing of medicines. Researchers and scientists have been striving hard to discover and invent new and diversified chemical combinations. These formulated chemicals are useful against the resistant activity of microbes and can be used for treatment of different ailments other than those caused by microbes. One of these efforts is to synthesize efficient, effective, and easily accessible organic compounds with no or the least side effects. Additionally, these compounds also play a key role in the agricultural, industrial, and environmental domains. Hydrazones have attracted the attention of medicinal chemists because of their multiple biological applications. In this scenario, synthetic chemists working on the medicinal area across the globe have developed hydrazones with improved biological activity and low toxicity profiles. The medicinal importance or bioactive potential of any chemical architecture depends upon their molecular structures and binding cites present.1 The structure of hydrazones has all the necessary features required for the biological applications as well as further modification by complexation as shown in Figure 1.

Figure 1.

Figure 1

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Structural and functional diversity of the hydrazine functionality.

Modern chemists have triumphed in making such synthetic scaffolds with the potential to treat a broad range of maladies. Hydrazones are also among such class of important chemical building blocks that have a broad range of biological activities.2,3 Hydrazones can potentially act as antimicrobial,4 analgesic, anti-inflammatory,5 antihypertensive,6 antitubercular,7 anti-HIV,8 cardioprotective,9 antimalarial,10 antioxidant,11 anticancer,12 antidepressant,13 and anticonvulsant14 agents (Figure 2).

Figure 2.

Figure 2

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Examples of some valuable bio-active hydrazones.

It is also very interesting to mention that materials with nonlinear optical (NLO) behavior have substantial applications in many arenas including biophysics, nuclear science, chemical dynamics, medicine, materials, and surface interface presentations.15 Therefore, it is an interesting scenario to find out the nonlinear optical (NLO) applications of the newly synthesized organic compounds. Recently, interdisciplinary studies are getting immense attention and synthetic chemists are employing computational studies of newly synthesized organic compounds for investigation of their kinetic properties and revealing their electronic structures. The computational codes and calculations of density functional theory (DFT) are used to investigate stability, potential of non-covalent interactions, and the structures of newly synthesized organic compounds by utilizing/exploiting their electronic and magnetic properties. The non-covalent interactions help in the synthesis of the targeted novel material that plays a key role in catalysis as well as enhances the bioactive potential of synthesized compounds.16 In the current study, we are reporting the synthesis, spectroscopic characterization, and DFT/TD-DFT studies that reveal non-covalent interactions in novel pyridine-based halogenated hydrazones.

Materials and Methods

General Procedure

In the current research work, we have synthesized novel hydrazones from a heterocyclic phenolic precursor. Analytical grade reagents and solvents were purchased and used without further purification in the whole experimental work. In order to monitor the reaction progress, TLC cards coated with silica gel (0.25 mm thickness) with F-254 fluorescent indicator on the Al sheet were used. The NMR spectra were recorded on Bruker Avance, A-V. NMR spectrometer where 400 MHz was used for 1H-NMR and 100 MHz was used for 13C-NMR. For the FTIR analysis, a Shimadzu IR Prestige-21 model instrument was used. Chemical shifts (δ) are reported in parts per million (ppm) relative to the residual solvent signals, and coupling constants (J) are reported in hertz.

Synthesis of Ethyl 2-(6′-Chloroazin-2-yl)-ox-ethanoate (3)

The synthesis of ethyl 2-(6′-chloroazin-2-yl)-ox-ethanoate 3 was performed according to the reported method.17 Briefly, a mixture of 6-chloro-2-hydroxy pyridine (100 mg, 0.78 mmol) 1 and 128 mg of anhydrous K2CO3 was heated in 15 mL of dry acetone for 20 min in 50 mL round bottom flask. To this mixture, 0.33 mL of ethyl-chloroacetate 2 was added dropwise and the reaction mixture was refluxed for 3 h. After the completion (monitored by TLC), the reaction mixture was cooled to room temperature and filtered off. The solvent was evaporated under reduced pressure. The targeted compounds were purified by column chromatography using n-hexane/ethylacetate.

IR ύmax (cm–1) KBr: 1739 (O–C=O); 1H-NMR δH (400 MHz, CDCl3) in ppm, 1.28 (t, J = 6.7 Hz, 3H), 4.24 (q, J = 6.7 Hz, 2H), 4.86 (s, 2H), 6.77 (d, J = 7.1 Hz, 1H), 6.93 (d, J = 6.9 Hz, 1H), and 7.55 (t, J = 7.2 Hz, 1H); 13C-NMR δC (100 MHz, CDCl3) in ppm, 14.1, 61.1, 62.8, 109.2, 117.2, 141.0, 148.0, 162.0, and 168.6.

Synthesis of 2-(6′-Chloroazin-2′-yl) Oxy-aceto-hydrazide (4)

A mixture of ethyl 2-(6′-chloroazin-2-yl)-ox-ethanoate 3 (131 mg, 0.61 mmol) and N2H4.H2O (0.09 mL, 1.83 mmol) in ethanol was refluxed for 3 h.18 On completion (monitored by TLC), the reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The final product was purified using column chromatography yielding 89 mg of the targeted hydrazide 4 (73%).

IR ύmax (cm–1) KBr: 1639 (HN–C=O), 2926 (H-bonded N–H), 3298 (non-H-bonded N–H); UV λmax(nm) 272; 1H NMR (400 MHz, DMSO) δ 4.29 (s, 2H, hydrazinic-NH2), 4.71 (s, 2H), 6.90 (d, J = 7.5 Hz, 1H′), 7.11 (d, J = 7.3 Hz, 1H), 7.79 (t, J = 7.9 Hz, 1H), and 9.30 (s, 1H, amidic N–H).

General Procedure for the Synthesis of 2-[(6′-Chloroazin-2′-yl)oxy]-N′-benzylidene-aceto-hydrazones (CPFH, BCPH, and CCPH)

A mixture of 2-(6′-chloroazin-2′-yl) oxy-aceto-hydrazide 4 (98 mg, 0.48 mmol) and the substituted aromatic aldehydes 5 (0.54 mmol) in dry ethanol was refluxed for 2 h. The reaction was monitored by TLC; after completion, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Final purification was achieved through column chromatography.

2-[(6′-Chloroazin-2′-yl)oxy]-N′-(2-fluorobenzylidene) Aceto-Hydrazone (CPFH)

IR ύmax (cm–1) KBr: 1587 (iminic −C=N), 1689 (amidic −C=O), 3084 (H-bonded −N–H); UV λmax(nm) 277;1H NMR (400 MHz, DMSO) δ 11.69 (s, 1H), 8.23 (s, 1H), 7.93 (t, J = 7.0 Hz, 1H), 7.80 (m, J = 6.2 Hz, 1H), 7.51–7.46 (m, 1H), 7.29 (dd, J = 9.0, 4.9 Hz, 2H), 7.11 (d, J = 7.2 Hz, 1H), 6.95 (d, J = 7.9 Hz, 1H), 5.35 (s, 2H); 13C NMR (101 MHz,DMSO) δ 168.6, 162.4, 159.4, 146.7, 142.2, 136.7, 131.8, 126.3, 124.9, 116.9, 116.1, 115.9, 109.6, and 62.8.

2-[(6′-Chloroazin-2′-yl)oxy]-N′-(2-chlorobenzylidene) Aceto-Hydrazone (CCPH)

IR ύmax(cm–1) KBr: 1589 (iminic C=N), 1687 (amidic C=O), 3094 (H-bonded N–H); UV λmax(nm) 281; 1H NMR (400 MHz,DMSO) δ 11.75 (s, 1H), 8.40 (s, 1H), 8.02–7.97 (m, 1H), 7.80 (t, J = 7.9 Hz, 1H), 7.53 (d, J = 7.4 Hz, 1H), 7.44 (m, J = 9.5, 4.4 Hz, 3H), 7.10 (d, J = 7.5 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H),5.36 (s, 2H); 13C NMR (101 MHz, DMSO) δ 168.7, 162.4, 160.6, 146.8, 145.5, 142.2, 136.1, 133.6, 130.6, 129.6, 125.7, 116.8, 109.5, and 62.9.

2-[(6′-Chloroazin-2′-yl)oxy]-N′-(2-bromobenzylidene) Aceto-Hydrazone (BCPH)

IR ύmax(cm–1) KBr: 1583 (iminic −C=N), 1690 (amidic −C=O), 3074 (H-bonded −N–H); UV λmax(nm) 280; 1H NMR (400 MHz, DMSO) δ 11.77 (s, 1H), 8.37 (s, 1H), 7.97 (dd, J = 7.8, 1.5 Hz, 1H), 7.79 (t, J = 6.3 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 7.7 Hz, 1H), 7.37 (dd, J = 10.8, 4.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 5.36 (s, 2H); 13C NMR (101 MHz,DMSO) δ 168.7, 164.1, 160.1, 146,8, 145.5, 142.2, 133.1, 132.6, 131.6, 128.1, 127.2, 123.3, 116.9, 109.6, and 62.9.

Results and Discussion (Synthesis)

The targeted ester 3 was synthesized by treating 6-chloro-2-hydroxy pyridine 1 with ethyl chloroacetate in a polar aprotic solvent, i.e., acetone. This reaction is an example of a nucleophilic substitution reaction and follows the SN2 mechanism where the 6-chloro-2-hydroxy pyridine 1 molecule produced a phenoxide ion, which acts as a nucleophile and substituted the Cl of ethyl chloroacetate to give the targeted ester 3. The appropriate amount of prepared ester 3 was treated with hydrazine monohydrate in ethanol, which facilitates the formation of the substituted product 2-(6′-chloroazin-2′-yl) oxy-aceto-hydrazide 4 by the elimination of an ethoxide ion. Finally, the prepared hydrazide 4 was coupled with suitable ortho-substituted aromatic aldehydes in ethanol to get the targeted hydrazones (Scheme 1).

Scheme 1. Synthesis of Hydrazones, Starting from Heterocyclic Phenolic Moiety.

Scheme 1

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In the current research work, we successfully synthesize novel hydrazones from hetero cyclicphenolic moiety. The formation of these compounds was confirmed by different spectroscopic techniques. In the IR spectrum, the disappearance of the broad pyridinic −OH peak of 1 from 3070 cm–1 and appearance of a signal of the aliphatic ester supported the formation of targeted ester 3. The formation of ester 3 was also proved by proton NMR, in 1H-NMR; the emergence of the new aliphatic region by the appearance of a quartet and triplet at 4.24 and 1.28 ppm confirmed the formation of the ethoxy group. In the case of compound 4, the disappearance of the aliphatic ester signal and appearance of two broad peaks about 3298 and 2926 cm–1of −NH stretching confirmed the formation of targeted hydrazide 4. In 1H-NMR, the disappearance of two aliphatic peaks of 3 from 1.28 and 4.24 ppm and the emergence of two broad peaks at 4.29 and 9.30 ppm having integration equal to two and one protons, respectively, authenticated the formation of −NH and −NH2 groups. Finally, the formation of targeted hydrazone was confirmed by the disappearance of two peaks from 3298 and 2926 cm–1 of −NH stretching and emergence of one broad peak of −NH at 3000 ± 2 cm–1 as well as the appearance of two signals at 1692 ± 1 and 1575 ± 1 cm–1 endorsed the development of hydrazodic (−C=O) and iminic (HC=N−) functional groups, respectively. In 1H-NMR, the emergence of new peaks in the aromatic region authenticated the coupling between 4 and aromatic aldehydes. Moreover, a new singlet peak of (HC=N-) at 8.23 ppm having integration equal to one proton added weight to the formation of hydrazones CPFH, CCPH, and BCPH.

Computational Procedure

All quantum chemical calculations were carried out using the Gaussian 09 program package.19 The molecular geometries of acetohydrazydederivatives: (E)-2-((6-chloropyridine-2-yl)oxy)-N″-(2-fluorobenzylidene) acetohydrazide (CPFH), (E)-N″-(2-bromobenzylidene)-2-((6-chloropyridine-2-yl)oxy) acetohydrazide (BCPH), and (E)-N″-(2-chlorobenzylidene)-2-((6-chloropyridine-2-yl)oxy) acetohydrazide (CCPH) were completely optimized without symmetry restrictions by applying the CAM-B3LYP/6-311G (d,p) level.20 The final optimized geometries of CPFH, BCPH, and CCPH were used to calculate FT-IR vibrational frequencies at the same level for confirmation of their stability. Subsequently, no imaginary frequency was observed in any FT-IR analysis of studied compounds, which confirmed their stability. The Gaussian 09 package has been used for natural bond orbital calculations by applying NBO 3.1 program at the CAM-B3LYP/6-311G (d,p) level. The vertical excitation energies, electronic transitions, oscillator strengths, and HOMO and LUMO energies were calculated with the help of time-dependent DFT (TD-DFT) investigation utilizing the CAM-B3LYP/6-311G (d,p) approach. For NLO analysis of the molecules, the electronic dipole moment (μ), linear polarizability (α), and first order hyperpolarizabilities (β) were computed at the aforesaid DFT level. The input files were organized with the help of Avogadro,21 Gaussview 5.0,22 GaussSum,23 and Chemcraft24 programs. Same softwares were employed for interpreting output files.

Results and Discussion (Computational)

The spectral analysis confirmed the synthesis of targeted compounds. After comformation, the DFT exploration of these newly synthesized molecules were carried out; the details are given as bellow.

Natural Bond Orbital (NBO) Analysis

The NBO investigation has been confirmed to be a persuasive tool for chemical explanation of hyper conjugative forces and electronic density redistribution in different bonding as well as antibonding orbitals. The second order perturbation approach was used to determine the delocalized type interactions. The probe was performed by investigating entire conceivable interactions between donor Lewis-type NBOs and acceptor non-Lewis NBOs.25 Natural bond orbitals (NBOs) described the Lewis-like molecular bonding pattern of electron pairs. The natural bond orbital calculations were performed using the NBO 3.1 program26 as implemented in the Gaussian09 package at the DFT/CAM-B3LYP/6-311G (d,p) level. According to the second order perturbation approach, the stabilization energy formula could be shown by eq 1.27

graphic file with name ao0c02128_m001.jpg 1

Here, stabilization energy = E(2), donor orbital occupancy = qi, the diagonal = F(i.j), and the off-diagonal elements = εj , εI are NBO Fock matrix elements.28 The NBO analysis for CPFH, CCPH, and BCPH has been elaborated in Tables S1–S3. However, some representative values are summarized in Table 1.

Table 1. NBO Analysis of CPFH, CCPH, and BCPHa.

comp donor (i) types acceptor (j) types E(2) E(j) – E(i) (au) F(i,j) (au)
CPFH C5-N6 σ C1-Cl10 σ* 5.89 1.13 0.073
  C25-C28 π C22-C23 π* 34.07 0.36 0.101
  C1-N6 π C4-C5 π* 36.31 0.42 0.114
  C4-C5 π C2-C3 π* 38.71 0.38 0.109
  C2-C3 π C1-N6 π* 46.48 0.33 0.114
  O16 LP(2) C15-N17 σ* 31.64 0.83 0.147
  N17 LP(1) N19-C20 π* 32.38 0.39 0.105
  O11 LP(2) C4-C5 π* 38.99 0.44 0.124
  N17 LP(1) C15-O16 π* 73.44 0.39 0.153
CCPH C 22-C24 σ C23-Cl32 σ* 6.51 0.96 0.071
  C24-C26 π C25-C28 π* 31.93 0.37 0.097
  C1-N6 π C4-C5 π* 36.35 0.42 0.114
  C4-C5 π C2-C3 π* 38.64 0.38 0.109
  C2-C3 π C1-N6 π* 46.45 0.33 0.114
  O16 LP(2) C15-N17 σ* 31.77 0.83 0.147
  N17 LP(1) N19-C20 π* 32.9 0.39 0.105
  O11 LP(2) C4-C5 π* 38.86 0.44 0.124
  N17 LP(1) C15-O16 π* 72.72 0.39 0.153
BCPH C22-C24 σ C22-C23 σ* 6.73 1.39 0.086
  C24-C26 π C25-C28 π* 31.65 0.37 0.097
  C1-N6 π C4-C5 π* 36.33 0.42 0.114
  C4-C5 π C2-C3 π* 38.64 0.38 0.109
  C2-C3 π C1-N6 π* 46.44 0.33 0.114
  O16 LP(2) C15-N17 σ* 31.76 0.83 0.147
  N17 LP(1) N19-C20 π* 32.77 0.39 0.105
  O11 LP(2) C4-C5 π* 38.89 0.44 0.124
  N17 LP(1) C15-O16 π* 72.82 0.39 0.153
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a

Comp = compounds, LP = lone pair, (j) acceptor, (i) donor, E(2) means energy of hyper conjugative interaction (stabilization energy), F(i, j) is the Fock matrix element between i and j NBO orbitals, and E(j) – E(i) is the energy difference between donor and acceptor i and j NBO orbitals.

For CPFH, the most important LP→ π* interactions were observed as LP(1)N17 → π*C15-O16, LP(1)N17 → π*C19-C20, and LP(2)O11 → π*C4-C5 with stabilization energies of 73.44, 32.28, and 25.44 kcal/mol, respectively. Similarly, another important LP → σ* transition was described as LP(2)O16 → σ*C15-N17 with 31.64 kcal/mol stabilization energy. Moreover, some prominent π → π* transition were found as πC4-C5 → π*C2-C3, πC1-N6 → π*C4-C5, πC25-C28 → π*C22-C23, and πC2-C3 → π*C1-N6 with energies as 46.48, 38.71, 34.07, and 9.44 kcal/mol, respectively. Herein, σ → σ* interaction could be observed as σ(N5-N6) →σ*(C1-Cl10) with least stabilization energy as 5.89 kcal/ mol.

For CCPH, the highest transition in the case of LP → π* could be described as LP(1)N17 → π*(C15-O16), yielding stabilization energy as 72.72 kcal/mol. Moreover, some other transitions were also observed like LP(2)O11 → π*(C4-C5) and LP(1)N17 → π*(N19-C20) with stabilization energies as 38.86 and 32.9 kcal/mol, respectively. Similarly, the most prominent interaction was found in LP(2)O16 → σ*C15-N17 with 31.77 kcal/mol. Furthermore, π → π* transitions were observed as π(C2-C3) → π*(C1-N6), π(C4-C5) → π*(C2-C3), π(C1-N6) → π*(C4-C5), and π(C24-C26) → π*(C25-C28), yielding stabilization energies, i.e., 46.45, 38.64, 36.35, and 31.93 kcal/mol, respectively.

For BCPH, the most prominent transitions take place as LP(1)N17 → π*C15-O16, LP(2)O11 → π*C4-C5, LP(1)N17 → π*N19-C20 with stabilizations as 72.82, 38.89 and 32.77 kcal/mol, respectively. Moreover, the least important σ → σ* transition was described in σ(C22-C24) → σ*(C22-C23) with stabilization energy as 6.73 kcal/mol. Herein some significant π → π* interactions were also observed as π(C2-C3) → π*(C1-N6), π(C4-C5) → π*(C2-C3), π(C1-N6) → π*(C4-C5), and π (C24-C26) → π*(C25-C28) affording stabilization energies as 46.44, 38.64, 36.33 and 31.65 kcal/mol, respectively. From our preceding discussion, it could be concluded that the stability of the compounds was due to hyper conjugation and extended conjugation. The NBO numbering scheme for entitled compounds can be seen in Figure S8.

Natural Population Analysis

Natural population analysis (NPA) plays a vital role in quantum mechanical calculations.29 Natural population analysis was remarkably important in obtaining the total atomic charge values, and these natural charges were derived using natural bond orbital (NBO) analysis.30 The calculations of atomic charges within a molecule along with electron distribution were considered as effective descriptors to determine the non-covalent interactions (NCIS).31 The atomic charges of CPFH, CCPH, and BCPH were obtained by NPA and are plotted in Figure 3.

Figure 3.

Figure 3

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Charge distribution analysis for CPFH, CCPH, and BCPH.

In CPFH, all the hydrogen atoms were positively charged, while all C atoms except C1, C5, C12, C15, C20, and C23 were negatively charged. Herein, it could also be observed that N17 contained negative charge (−0.3091e), while C5 has more positive charge (0.3461e). Similarly, in CCPH, a N17 atom was found more negatively charged (−0.3079e). Moreover, the atoms of carbons were negatively charged excluding C1, C5, C15, C20, and C25 owing to attachment with N and O atoms. In BCPH it has been observed that all H atoms possessed a positive charge, whereas a negative charge was present on all C atoms except C5, C15, and C20 due to the presence of electronegative N and O atoms (Figure 3).

FT-IR Analysis

The intensities, nature of vibrational modes, and harmonic frequencies of CPFH, CCPH, and BCPH were studied at the DFT/CAM-B3LYP/6-311G (d,p) level.

C–H Vibrations

A literature study showed that aromatic C–H vibrations were situated at 3100–3000 cm–1.32 Herein, the C–H stretching symmetric modes of vibration in aromatic and hetero aromatic rings were situated at 3249, 3249, and 3248 cm–1 for CPFH, CCPH, and BCPH, respectively. For CPFH, CCPH, and BCPH, the C–H antisymmetric stretching vibrations were found in the range of 3211–3208 cm–1. The rocking stretching vibration were located at 1665–1282, 1654–1307, and 1654–1204 cm–1, which were in excellent concurrence with experimental data as 1598–1271, 1584–1458, and 1587–1273 cm–1, respectively. Moreover, the scissoring vibrations were seen at 1696–1654, 1679–1654, and 1675–1641 cm–1 for CPFH, CCPH, and BCPH. Herein, for CPFH, the simulated C–H wagging vibrational frequencies at 1274, 1130, 1029, 878, and 789 cm–1 were found with an excellent agreement with experimental data as 1271, 1152, 1062, 874, and 772 cm–1, respectively (Table S4). Similarly, in CCPH and BCPH, wagging vibrations were calculated at 1274, 1028, 822, and 787 cm–1 and 1028, 823, and 746 cm–1 (DFT) compared to 1271, 1055, 874, and 768 cm–1 and 1076, 876, and 775 cm–1 (experimental) were found in good concurrence, respectively (Tables S5 and S6). Similarly, in CCPH and BCPH, the calculated and experimental wagging vibrations were found in good agreement as 1274, 1028, 822, and 787 cm–1 and 1028, 823, and 746 cm–1 (DFT) and 1271, 1055, 874, and 768 cm–1 and 1076, 876, and 775 cm–1 (experimental), respectively (Tables S5 and S6).

C–C Stretching Vibration

The literature study revealed that C–C stretching vibrations were located at 1650–1400 cm–1,33 while the C–C stretching vibrational wave numbers in CPFH, CCPH, and BCPH were found at 1696–1654, 1679–1654, and 1675–1641 cm–1 (DFT), which was in close agreement to the literature data. Furthermore, in CPFH, the simulated C–C vibrations could be seen at 926 and 878 cm–1, which was in excellent agreement with experimental data as 951 and 874 cm–1, respectively (Table S4). Similarly, for CCPH and BCPH, stretching vibrational wavenumbers were found at 1478 and 822 cm–1 and 1479, 1273, and 927 cm–1, which strongly supported the experimental data as 1458 and 874 cm–1 and 1435, 1273, and 953 cm–1, respectively (Tables S5 and S6).

C–O Vibration

The C=O bands were located at 1666–1651 cm–1.34−37 In CPFH, CCPH, and BCPH the calculated C=O band was found at 1845 cm–1, which nicely correlated with experimental values as 1874, 1856, and 1869 cm–1, respectively (Tables S4–S6).

N–H Vibrations

The N–H bands were located at 3500–3000 cm–1.31 In CPFH, CCPH, and BCPH, the N–H stretching bands were detected at 3541, 3391, and 3540 cm–1, respectively (DFT). Some other N–H bands of entitled compounds seen at 1845, 1845, and 1869 cm–1 strongly supported the experimental values as 1874, 1856, and 1869 cm–1, respectively (Tables S4–S6).

C–N Vibrations

The C–N vibrations were found at 1382–1266 cm–1, which is normally the result for the combination of vibrational bands of other functional groups.38 In CPFH, CCPH, and BCPH, the C–N stretching bands were seen at 1740, 1734, and 1733 cm–1, respectively. Furthermore, the C–N stretching frequency in pyridine was located at 1667 cm–1 for CPFH, CCPH, and BCPH, showing an excellent concurrence to the experimental values as 1688, 1690, and 1689 cm–1, respectively (Tables S4–S6). In CPFH, some additional vibrations were seen at 1204, 1119, and 920 cm–1 (Table S4). Similarly, in CCPH and BCPH, stretching vibrational wavenumbers were found at 1478, 1204, and 926 cm–1 and 1307, 1273, and 1204 cm–1, respectively (Tables S5 and S6).

C–X Vibrations

The C–F stretching modes in CPFH were found at 1282, 1119, and 1068 cm–1 (Table S4), while in CCPH, the C–Cl stretching modes were detected at 1069, 822, and 728 cm–1(Table S5). Similarly, in BCPH, the C–Br stretching bands have been seen at 1054 and 870 cm–1(Table S6).

UV–Vis Analysis

The UV–visible spectral study was conducted using TD-DFT/CAM-B3LYP/6-311G (d,p) approach to explain charge transfer, absorption properties, and vertical excitations of the entitled compounds. This study also provides significant information about compound energy gaps and band structures.39 TD-DFT-based excitation energies (E), wavelengths of maximum absorption (λmax), oscillator strengths (f), and the major and minor orbitals contributions are tabulated in Table 2.

Table 2. Excitation Energies, Wave Lengthsand Oscillator Strengths of CPFH, CCPH, and BCPHa.

comp DFT λ (nm) expt λ (nm) E (cm–1) f MO contributions
CPFH 263 279 37,956 0.765 H→L (91%)
  244   40,974 0.0657 H-2→L (57%), H-1→L (11%), H→L + 3 (19%), H4→L + 3 (3%), H-2→L + 1 (3%), H-2→L + 4 (2%), H→L (3%)
  237   42,228 0.1116 H-2→L + 1 (10%), H-1→L + 1 (70%), H-6→L + 2 (8%), H-2→L (2%), H-1→L (3%), H→L + 1 (2%)
  232   43,020 0.0012 H-2→L + 1 (10%), H-1→L + 1 (70%), H-6→L + 2 (8%), H-2→L (2%), H-1→L (3%), H→L + 1 (2%)
  224   44,565 0.0003 H-7→L (21%), H-5→L (47%), H-3→L (10%), H-3→L + 4 (10%), H-5→L + 9 (3%), H-3→L + 9 (3%)
  216 218 46,378 0.0034 H-7→L + 1 (58%), H-5→L + 1 (30%) H-7→L (3%), H 3→L + 1 (3%)
CCPH 265 278 37,706 0.7435 H→L (93%)
  250   39,927 0.0425 H-1 →L (61%), H →L + 3 (22%), H-4 →L + 3 (4%), H-2 →L (6%), H-1 →L + 4 (2%)
  236   42,233 0.1153 H-2 →L + 1 (73%), H-6 →L + 2 (8%), H-2 →L (3%), H-1 →L + 1 (8%), H →L + 1 (2%)
  235   42,611 0.0013 H-5 →L (26%), H-3 →L (46%), H-3 →L + 4 (17%), H-7 →L (3%), H-5- →L + 9 (2%)
  227   44,072 0.0002 H-7 →L (12%), H-5 →L (45%), H-3 →L (16%), H-3 →L + 4 (14%), H-9 →L (2%), H-5 →L + 9 (2%), H-3 →L + 9 (3%)
  216 220 46,380 0.0034 H-7 →L + 1 (69%), H-5 →L + 1 (20%), H-7 →L (2%), H-3 →L + 1 (3%)
BCPH 267 279 37,593 0.7107 H→L (93%)
  252   39,699 0.0585 H-1→L (67%), H→L + 3 (20%), H-5→L + 3 (3%), H-1→L + 5 (2%)
  237   42,227 0.1156 H-2→L + 1 (80%), H-6→L + 2 (8%), H-2→L (3%), H→L + 1 (2%)
  235   42,493 0.0015 H-8→L (14%), H-4→L (19%), H-3→L (45%), H-3→L + 5 (14%), H-3→L + 9 (4%)
  227   43,960 0.0001 H-8→L (18%), H-4→L (37%), H-3→L (17%), H-3→L + 5 (17%), H-3→L + 9 (4%)
  217 220 46,006 0.0001 H-1→L + 4 (47%), H→L + 4 (46%), H-9→L + 4 (3%)
Open in a new tab
a

H = HOMO, L = LUMO, expt = experimental, f = oscillator strength, E = energy, and MO = molecular orbital.

The calculated λmax value, f value, and dominant transition in the gas phase were found to be 263 nm, 0.765 with H→L (91%) for CPFH, 265 nm, 0.7435 with H→L (93%) for CCPH, and 267 nm, 0.7107 with H→L (93%) for BCPH, respectively (Table 2). The experimental UV–vis absorption bands were recorded in the range of 218–279, 220–278, and 220–279 nm for CPFH, CCPH, and BCPH, respectively (Table 2 and Figure S7). In CPFH, the calculated λmax values observed at 263 and 216 nm exhibits good harmony with experimental λmax values found at 279 and 218 nm, respectively. The calculated λmax values (265 and 216 nm) and experimental λmax values (278 and 220 nm) in CCPH correlated adequately with each other. Similarly in BCPH, 267 and 217 nm are the computed λmax values, which shows good concurrence with experimental λmax values observed at 279 and 220 nm respectively. The preceding discussion precisely indicates that calculated and computed results in investigated compounds CPFH, CCPH, and BCPH correspond in good agreement to each other.

Frontier Molecular Orbital (FMO) Analysis

The frontier molecular orbitals (FMOs) consist of highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO). FMOs can play a significant role during molecular interactions.40 The chemical reactivity and stability might be determined by the energy gap of FMO.41−48 The electronic properties of CPFH, CCPH, and BCPH were determined by FMOs at the CAM-B3LYP/6-311G (d,p) level. The FMOs consist of HOMO, LUMO, HOMO – 1, LUMO + 1, HOMO – 2, LUMO + 2, and their energy gaps (ΔE) are presented in Table 3. As in CPFH, CCPH, and BCPH, energy gaps were found as 7.278, 7.241, and 7.229 eV, respectively. The decreasing order of energy gap of entitled compounds was found as CPFH > CCPH > BCPH, and a pictographic display of FMOs for CPFH, CCPH and BCPH is presented in Figure 4.

Table 3. EHOMO, ELUMO, and Energy Gap of Entitled Compoundsa.

CPFH
 CCPH
 BCPH
MO(S) E (eV) ΔE (eV) MO(S) E (eV) ΔE (eV) MO(S) E (eV) ΔE (eV)
HOMO –7.793 7.278 HOMO –7.853 7.241 HOMO –7.833 7.229
LUMO –0.515   LUMO –0.612   LUMO –0.604  
HOMO – 1 –8.601 8.452 HOMO – 1 –8.580 8.414 HOMO – 1 –8.479 8.315
LUMO + 1 –0.149   LUMO + 1 –0.166   LUMO + 1 –0.164  
HOMO – 2 –8.637 9.081 HOMO – 2 –8.627 8.199 HOMO – 2 –8.622 9.053
LUMO + 2 0.444   LUMO + 2 0.428   LUMO + 2 0.431  
Open in a new tab
a

MO = molecular orbital, E(HOMO) = energy of HOMO, E(LUMO) = energy of LUMO, ΔE (eV) = E(LUMO) – E(HOMO).

Figure 4.

Figure 4

Open in a new tab

Frontier molecular orbitals of CPFH, CCPH, and BCPH.

The electronic density in HOMO for CPFH was located on the (fluorobenzylidene) acetohydrazide, while the electronic density in LUMO for CPFH was located on the (fluorobenzylidene) acetohydrazide with the small contribution from nitrogen atoms of pyridine as shown in Figure 4. However, in CCPH, the electronic density in HOMO was dispersed on the (fluorobenzylidene) methoxyacetohydrazide fragment, whereas the electron density in LUMO was dispersed on the (fluorobenzylidene) methoxyacetohydrazide fragment and in a small portion of the pyridine (Figure 4). On the other side, for BCPH, the electronic density in HOMO was located on the (2-bromobenzylidene) acetohydrazide, while in LUMO, it was dispersed on the (2-bromobenzylidene) acetohydrazide fragment, which was almost the whole structure except the bromine group and small effect on carbon and nitrogen of pyridine.

Global Reactivity Parameters

The energies of HOMO and LUMO were used to depict stability as well as reactivity of CPFH, BCPH, and CCPH. The electron affinity (A) and ionization potential (I) could be calculated by using eqs 2 and 3.49

graphic file with name ao0c02128_m002.jpg 2
graphic file with name ao0c02128_m003.jpg 3

Here, global hardness and electronegativity50 were obtained using eqs 4 and 5.

graphic file with name ao0c02128_m004.jpg 4
graphic file with name ao0c02128_m005.jpg 5

The charge transfer process could be obtained by calculations of electrophilicity (ω).

The electrophilicity was calculated by eq 6, and it was used to establish the charge transfer process, which described the variations of energy.51−56

graphic file with name ao0c02128_m006.jpg 6

The global softness (σ) could be calculated by using eq 7.

graphic file with name ao0c02128_m007.jpg 7

The results obtained from eqs 2–7 are presented in Table 4.

Table 4. Global Reactivity Descriptors for CPFH, CCPH, and BCPHa.

compounds I A X η μ ω σ
CPFH 7.793 0.515 4.154 3.639 –4.154 2.371 0.1374
CCPH 7.853 0.612 4.233 3.621 –4.233 2.474 0.1381
BCPH 7.833 0.604 4.219 3.615 –4.219 2.462 0.1383
Open in a new tab
a

Ionization potential (I), electro negativity (X), electron affinity (A),chemical potential (μ), global softness (σ), global hardness (η), and global electrophilicity (ω).

Overall, the electron donating and accepting abilities were described by ionization potential and electron affinity. In the studied molecules, the ionization potential was found to be much higher than electron affinity (A) values. The stability as well as reactivity of a chemical system was correlated to chemical potential and global hardness values.57 The stability had a direct relation with global hardness, whereas it had an inverse relationship to its reactivity.58

The order of global hardness was found as follows: [CPFH (η = 3.639 eV)] > [CCPH(η = 3.621 eV)] > [BCPH (η = 3.615 eV)]. These findings in context of stability as well as reactivity showed that CPFH was more stable and less reactive as compared to BCPH and CCPH.

Nonlinear Optical (NLO) Properties

Nowadays, organic compounds are explored as potential candidates for NLO application due to their low cost and large nonlinear response.59 NLO is helpful in frequency shifting optical modulation, optical logic, optical switching, and optical memory in areas like telecommunications, optical interconnections, and signal processing.60−62 Electronic properties are considered to be responsible for the strength of optical response, which in turn depends on the total molecular dipole moment (μ), linear response (polarizability, α), and nonlinear responses (hyperpolarizabilities, β, γ, etc.).63−65 The synthesized compounds CPFH, BCPH, and CCPH were studied at the CAM-B3LYP/6-311G (d,p) level for the evaluation of their NLO behavior. The diagonal elements of eq 8 were considered for estimating the average polarizability <α>.

graphic file with name ao0c02128_m008.jpg 8

First hyperpolarizability (βtot) has been computed from eq 9.

graphic file with name ao0c02128_m009.jpg 9

For CPFH, CCPH, and BCPH, the average linear polarizabilities <α> were obtained as 197.698, 208.607, and 214.417 au, respectively (Table 5). The dipole moment (μ) of CPFH, CCPH, and BCPH were found to be 2.184, 2.53,1 and 2.512D, respectively (Table 5). The increasing order of dipole moment of entitled compounds was noticed as CPFH < BCPH < CCPH. The second order polarizability (βtot) of CPFH, CCPH, and BCPH were calculated as 237.197, 182.828, and 188.506 au, respectively (Table 6). The increasing order of second order polarizability was noticed as CPFH < BCPH < CCPH. The urea molecule was frequently applied as standard molecule for comparative analysis.66 After comparison, βtot values of CPFH, BCPH, and CCPH were obtained greater than that of urea (βtot(urea) = 43 au).67

Table 5. Polarizability with Major Contributing Tensor (au) and Dipole Moments of the Compounds.

polarizability CPFH CCPH BCPH
αxx 288.066 296.872 301.461
αyy 223.919 244.863 254.400
αzz 81.109 84.086 87.390
αtotal 197.698 208.607 214.417
dipole moments CPFH CCPH BCPH
μx –2.0517 –2.2320 –2.3467
μy –0.7495 –1.1932 0.8968
μz 0.0030 0.0001 –0.0003
μtotal 2.184 2.531 2.512
Open in a new tab

Table 6. Computed First Hyperpolarizabilities (βtot) and Major Contributing Tensor (au) of the Compounds.

hyperpolarizability CPFH CCPH BCPH
βxxx 188.670 104.743 –64.403
βxxy –113.090 145.946 –151.038
βxyy –15.569 –18.288 –24.725
βyyy 237.472 –263.772 271.761
βxxz –0.060 0.021 –0.364
βyyz 0.019 –0.001 –0.006
βxzz –2.111 –1.700 –2.535
βyzz 40.011 –44.169 43.996
βzzz 0.065 –0.002 –0.023
βtot 237.197 182.828 188.506
Open in a new tab

Conclusions

In this study, halo-functionalized novel hydrazones derivatives CPFH, CCPH, and BCPH have been synthesized and characterized using FTIR, 1H-NMR, 13C-NMR, and UV–vis spectroscopic techniques. The experimental FT-IR and UV–visible spectroscopic analysis of CPFH, CCPH, and BCPH showed reasonable agreement to the corresponding DFT-based results. The NBO study confirmed that the presence of hyper-conjugative interactions and intramolecular charge transfer are a vital cause for the presence of stability of the investigated compounds. Global reactivity parameters indicated that CPFH, CCPH, and BCPH possess strong kinetic stability. The average linear polarizability <α> values were obtained as 197.698, 208.607, and 214.417 au for CPFH, CCPH, and BCPH, respectively. The increasing order of dipole moment was noticed as CPFH < BCPH < CCPH. The βtot of CPFH, CCPH, and BCPH were achieved as 237.197, 182.828, and 188.506, respectively. Furthermore, NLO comparative analysis brought to light that studied compounds have significant NLO response as compared to the prototype compound. Therefore, it is expected that this experimental–computational work may provide new horizons for CPFH, CCPH, and BCPH in the optoelectronic field.

Acknowledgments

M.A.A. and M.I. express appreciation to the Deanship of Scientific Research at King Khalid University Saudi Arabia for funding through general research grant number RGP.144/41. A.A. is thankful to HEC, Pakistan for the IPFP grant.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c02128.

  • Tables of Natural bond orbital (NBO) analysis and experimental and theoretical vibrational frequencies with assignments of CPFH, CCPH, and BCPH; experimental FTIR spectra and 1H and 13C-NMR data of CPFH, CCPH, and BCPH as well as their experimental UV spectra of reported compounds; and NBO numbering scheme of the investigated compounds (PDF)

Author Contributions

∇ A.A. and M.K. contributed equally to this work.

The authors declare no competing financial interest.

Supplementary Material

ao0c02128_si_001.pdf (1.4MB, pdf)

References

  1. Su X.; Aprahamian I. Hydrazone-based switches, metallo-assemblies and sensors. Chem. Soc. Rev. 2014, 43, 1963–1981. 10.1039/c3cs60385g. [DOI] [PubMed] [Google Scholar]
  2. Verma G.; Marella A.; Shaquiquzzaman M.; Akhtar M.; Ali M. R.; Alam M. M. A review exploring biological activities of hydrazones. J. Pharm. Bioallied Sci. 2014, 6, 69. 10.4103/0975-7406.129170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hussain I.; Ali A. Exploring the Pharmacological Activities of Hydrazone Derivatives: A Review. J. Phytochem. Biochem. 2017, 1, 1–5. [Google Scholar]
  4. Rane R. A.; Telvekar V. N. Synthesis and evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents. Bioorg. Med. Chem. Lett. 2010, 20, 5681–5685. 10.1016/j.bmcl.2010.08.026. [DOI] [PubMed] [Google Scholar]
  5. Duarte C. D.; Tributino J. L. M.; Lacerda D. I.; Martins M. V.; Alexandre-Moreira M. S.; Dutra F.; Bechara E. J. H.; De-Paula F. S.; Goulart M. O. F.; Ferreira J.; Calixto J. B.; Nunes M. P.; Bertho A. L.; Miranda A. L. P.; Barreiro E. J.; Fraga C. A. M. Synthesis, pharmacological evaluation and electrochemical studies of novel 6-nitro-3, 4-methylenedioxyphenyl-N-acylhydrazone derivatives: Discovery of LASSBio-881, a new ligand of cannabinoid receptors. Bioorg. Med. Chem. 2007, 15, 2421–2433. 10.1016/j.bmc.2007.01.013. [DOI] [PubMed] [Google Scholar]
  6. Gil-Longo J.; Laguna M. D. L. R.; Verde I.; Castro M. E.; Orallo F.; Fontenla J. A.; Calleja J. M.; Ravina E.; Teran C. Pyridazine derivatives. XI: Antihypertensive activity of 3-hydrazinocycloheptyl [1, 2-c] pyridazine and its hydrazone derivatives. J. Pharm. Sci. 1993, 82, 286–290. 10.1002/jps.2600820314. [DOI] [PubMed] [Google Scholar]
  7. Mahajan A.; Kremer L.; Louw S.; Guéradel Y.; Chibale K.; Biot C. Synthesis and in vitro antitubercular activity of ferrocene-based hydrazones. Bioorg. Med. Chem. Lett. 2011, 21, 2866–2868. 10.1016/j.bmcl.2011.03.082. [DOI] [PubMed] [Google Scholar]
  8. Ma X.-D.; Yang S.-Q.; Gu S.-X.; He Q.-Q.; Chen F.-E.; De Clercq E.; Balzarini J.; Pannecouque C. Synthesis and anti-HIV activity of Aryl-2-[(4-cyanophenyl) amino]-4-pyrimidinone hydrazones as potent non-nucleoside reverse transcriptase inhibitors. ChemMedChem 2011, 6, 2225–2232. 10.1002/cmdc.201100334. [DOI] [PubMed] [Google Scholar]
  9. El-Sabbagh O. I.; Shabaan M. A.; Kadry H. H.; Al-Din E. S. New octahydroquinazoline derivatives: synthesis and hypotensive activity. Eur. J. Med. Chem. 2010, 45, 5390–5396. 10.1016/j.ejmech.2010.08.064. [DOI] [PubMed] [Google Scholar]
  10. Fattorusso C.; Campiani G.; Kukreja G.; Persico M.; Butini S.; Romano M. P.; Altarelli M.; Ros S.; Brindisi M.; Savini L.; Novellino E.; Nacci V.; Fattorusso E.; Parapini S.; Basilico N.; Taramelli D.; Yardley V.; Croft S.; Borriello M.; Gemma S. Design, synthesis, and structure–activity relationship studies of 4-quinolinyl-and 9-acrydinylhydrazones as potent antimalarial agents. J. Med. Chem. 2008, 51, 1333–1343. 10.1021/jm7012375. [DOI] [PubMed] [Google Scholar]
  11. Musad E. A.; Mohamed R.; Saeed B. A.; Vishwanath B. S.; Rai K. M. L. Synthesis and evaluation of antioxidant and antibacterial activities of new substituted bis (1, 3, 4-oxadiazoles), 3, 5-bis (substituted) pyrazoles and isoxazoles. Bioorg. Med. Chem. Lett. 2011, 21, 3536–3540. 10.1016/j.bmcl.2011.04.142. [DOI] [PubMed] [Google Scholar]
  12. Liu W.-Y.; Li H.-Y.; Zhao B.-X.; Shin D.-S.; Lian S.; Miao J.-Y. Synthesis of novel ribavirin hydrazone derivatives and anti-proliferative activity against A549 lung cancer cells. Carbohydr. Res. 2009, 344, 1270–1275. 10.1016/j.carres.2009.05.017. [DOI] [PubMed] [Google Scholar]
  13. de Oliveira K. N.; Costa P.; Santin J. R.; Mazzambani L.; Bürger C.; Mora C.; Nunes R. J.; de Souza M. M. Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones. Bioorg. Med. Chem. 2011, 19, 4295–4306. 10.1016/j.bmc.2011.05.056. [DOI] [PubMed] [Google Scholar]
  14. Jain J.; Kumar Y.; Sinha R.; Kumar R.; Stables J. Menthone aryl acid hydrazones: a new class of anticonvulsants. J. Med. Chem. 2011, 7, 56–61. 10.2174/157340611794072689. [DOI] [PubMed] [Google Scholar]
  15. Khalid M.; Ali A.; Jawaria R.; Asghar M. A.; Asim S.; Khan M. U.; Hussain R.; Fayyaz ur Rehman M.; Ennise C. J.; Akram M. S. First Principles Study of Electronic and Nonlinear Optical Properties of A-D−π–A and D-A-D−π–A Configured Compounds Containing Novel Quinoline-Carbazole Derivatives. RSC Adv. 2020, 10, 22273–22283. 10.1039/D0RA02857F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maharramov A. M.; Mahmudov K. T.; Kopylovich M. N.; Pombeiro A. J.. Non-covalent interactions in the synthesis and design of new compounds; John Wiley & Sons: 2016. [Google Scholar]
  17. Ali A.; Khalid M.; Abid S.; Iqbal J.; Tahir M. N.; Raza A. R.; Zukerman-Schpector J.; Paixão M. W. Facile synthesis, crystal growth, characterization and computational study of new pyridine-based halogenated hydrazones: Unveiling the stabilization behavior in terms of noncovalent interactions. Appl. Organomet. Chem. 2020, 34, e5399 10.1002/aoc.5399. [DOI] [Google Scholar]
  18. Ali A.; Badawy M. E. I.; Shah R. A.; Rehman W.; Kilany Y. E.; Ashry E. S. H. E.; Tahir N. Synthesis, Characterization and In-Silico ADMET Screening of Mono- and Di-carbomethoxylated 6,6′-Methylenebis(2-cyclohexyl-4-methylphenol) and Their Hydrazides and Hydrazones. Der ChemicaSinica 2017, 8, 446–460. [Google Scholar]
  19. Frisch M. J.; Trucks G. W.; Schlegel H. B.; Scuseria G. E.; Robb M. A.; Cheeseman J. R.; Scalmani G.; Barone V.; Petersson G. A.; Nakatsuji H.; Li X.. Gaussian 09 citation; Gaussian Inc.: Wallingford, 2013. [Google Scholar]
  20. Tariq S.; Khalid M.; Raza A. R.; Rubab S. L.; de Alcântara Morais S. F.; Khan M. U.; Tahir M. N.; Braga A. A. C. Experimental and computational investigations of new indole derivatives: A combined spectroscopic, SC-XRD, DFT/TD-DFT and QTAIM analysis. J. Mol. Struct. 2020, 1207, 127803. 10.1016/j.molstruc.2020.127803. [DOI] [Google Scholar]
  21. Hanwell M. D.; Curtis D. E.; Lonie D. C.; Vandermeersch T.; Zurek E.; Hutchison G. R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminf. 2012, 4, 17. 10.1186/1758-2946-4-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Dennington R.; Keith T.; Millam J.. GaussView; Ver. 5.Semichem. Inc.:Wallingford CT,2009.
  23. O’boyle N. M.; Tenderholt A. L.; Langner K. M. Cclib: a library for package-independent computational chemistry algorithms. J. Comput. Chem. 2008, 29, 839–845. 10.1002/jcc.20823. [DOI] [PubMed] [Google Scholar]
  24. Zhurko G. A.; Zhurko D. A., ChemCraft; version 1.6. URL: http://www. chemcraftprog. com2009.
  25. Venkatesh G.; Govindaraju M.; Vennila P.. Experimental and theoretical spectral investigations of 5-chloro-ortho-methoxyaniline using FT-IR, FT-Raman and DFT analysis; NISCAIR-CSIR: India, 2016. [Google Scholar]
  26. Glendening E.; Reed A.; Carpenter J.; Weinhold F.. NBO; version 3.1; Gaussian. Inc.:Pittsburgh, PA, 2003.
  27. Muthu S.; Ramachandran G. Spectroscopic studies (FTIR, FT-Raman and UV–Visible), normal coordinate analysis, NBO analysis, first order hyper polarizability, HOMO and LUMO analysis of (1R)-N-(Prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine molecule by ab initio HF and density functional methods. Spectrochim. Acta, Part A 2014, 121, 394–403. 10.1016/j.saa.2013.10.093. [DOI] [PubMed] [Google Scholar]
  28. Liu J.-n.; Chen Z.-r.; Yuan S.-F. Study on the prediction of visible absorption maxima of azobenzene compounds. J. Zhejiang Univ., Sci., B 2005, 6, 584. 10.1631/jzus.2005.B0584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gunasekaran S.; Kumaresan S.; Arunbalaji R.; Anand G.; Srinivasan S. Density functional theory study of vibrational spectra, and assignment of fundamental modes of dacarbazine. J. Chem. Sci. 2008, 120, 315–324. 10.1007/s12039-008-0054-8. [DOI] [Google Scholar]
  30. Mulliken R. S. Electronic population analysis on LCAO–MO molecular wave functions. I. J. Chem. Phys. 1955, 23, 1833–1840. 10.1063/1.1740588. [DOI] [Google Scholar]
  31. Reed A. E.; Weinstock R. B.; Weinhold F. Natural population analysis. J. Chem. Phys. 1985, 83, 735–746. 10.1063/1.449486. [DOI] [Google Scholar]
  32. Varsányi G.Assignments for vibrational spectra of seven hundred benzene derivatives; Halsted Press: 1974, 1. [Google Scholar]
  33. Sathiyanarayanan D. N.Vibrational spectroscopy theory and application. New Age International Publishers: New Delhi: 2004, 424. [Google Scholar]
  34. Rittner R.; Ducati L. C.; Tormena C. F.; Fiorin B. C.; Braga C. B. Conformational preferences for some 5-substituted 2-acetylthiophenes through infrared spectroscopy and theoretical calculations. Spectrochim. Acta, A 2011, 79, 1071–1076. 10.1016/j.saa.2011.04.021. [DOI] [PubMed] [Google Scholar]
  35. Arshad M. N.; Birinji A. S.; Khalid M.; Asiri A. M.; Al-Amry K. A.; Aqlan F. M. S.; Braga A. A. C. Synthesis, spectroscopic, single crystal diffraction and potential nonlinear optical properties of novel pyrazoline derivatives: Interplay of experimental and computational analyses. Spectrochim. Acta, A 2018, 202, 146–158. 10.1016/j.saa.2018.04.069. [DOI] [PubMed] [Google Scholar]
  36. Liu Q.; Xu X.; Fang D.; Zheng J. Infrared study on solvent–solute interactions of 2-acetylthiophene in binary mixtures. Spectrochim. Acta, A 2004, 60, 397–400. 10.1016/S1386-1425(03)00237-3. [DOI] [PubMed] [Google Scholar]
  37. Thanigaimani K.; Arshad S.; Khalib N. C.; Razak I. A.; Arunagiri C.; Subashini A.; Sulaiman S. F.; Hashim N. S.; Ooi K. L. A new chalcone structure of (e)-1-(4-bromophenyl)-3-(napthalen-2-yl) prop-2-en-1-one: Synthesis, structural characterizations, quantum chemical investigations and biological evaluations. Spectrochim. Acta, A 2015, 149, 90–102. 10.1016/j.saa.2015.04.028. [DOI] [PubMed] [Google Scholar]
  38. Haress N. G.; El-Emam A. A.; Al-Deeb O. A.; Panicker C. Y.; Al-Saadi A. A.; Van Alsenoy C.; War J. A.; Srivastava S. K. Vibrational spectroscopic and molecular docking study of 2-benzylsulfanyl-4-[(4-methylphenyl)-sulfanyl]-6-pentylpyrimidine-5-carbonitrile, a potential chemotherapeutic agent. Spectrochim Acta, A 2015, 137, 569–580. 10.1016/j.saa.2014.08.112. [DOI] [PubMed] [Google Scholar]
  39. Suresh M.; Bahadur S. A.; Athimoolam S. Synthesis, growth and characterization of a new hydrogen bonded organic tosylate crystal: l-alaninium p-toluenesulfonate for second order nonlinear optical applications. J. Mater. Sci. Mater. 2016, 27, 4578–4589. 10.1007/s10854-016-4334-7. [DOI] [Google Scholar]
  40. Amiri S. S.; Makarem S.; Ahmar H.; Ashenagar S. Theoretical studies and spectroscopic characterization of novel 4-methyl-5-((5-phenyl-1, 3, 4-oxadiazol-2-yl) thio) benzene-1, 2-diol. J. Mol. Struct. 2016, 1119, 18–24. 10.1016/j.molstruc.2016.04.053. [DOI] [Google Scholar]
  41. Stolarczyk M.; Bryndal I.; Matera-Witkiewicz A.; Lis T.; Królewska-Golińska K.; Cieślak M.; Kaźmierczak-Barańska J.; Cieplik J. Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives. Acta Crystallogr., Sect. C: Struct. Chem. 2018, 74, 1138–1145. 10.1107/S2053229618012706. [DOI] [PubMed] [Google Scholar]
  42. Ali A.; Khalid M.; Marrugo K. P.; Kamal G. M.; Saleem M.; Khan M. U.; Concepción O.; de la Torre A. F. Spectroscopic and DFT/TDDFT insights of the novel phosphonate imine compounds. J. Mol. Struct. 2020, 1207, 127838. 10.1016/j.molstruc.2020.127838. [DOI] [Google Scholar]
  43. Srnec M.; Solomon E. I. Frontier molecular orbital contributions to chlorination versus hydroxylation selectivity in the non-heme iron halogenase SyrB2. J. Am. Chem. Soc. 2017, 139, 2396–2407. 10.1021/jacs.6b11995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Khalid M.; Ali A.; De la Torre A. F.; Marrugo K. P.; Concepcion O.; Kamal G. M.; Muhammad S.; Al-Sehemi A. G. Facile Synthesis, Spectral (IR, Mass, UV– Vis, NMR), Linear and Nonlinear Investigation of the Novel Phosphonate Compounds: A Combined Experimental and Simulation Study. ChemistrySelect 2020, 5, 2994–3006. 10.1002/slct.201904224. [DOI] [Google Scholar]
  45. Khalid M.; Ali A.; Adeel M.; Din Z. U.; Tahir M. N.; Rodrigues-Filho E.; Iqbal J.; Khan M. U. Facile preparation, characterization, SC-XRD and DFT/DTDFT study of diversely functionalized unsymmetrical bis-aryl-α, β-unsaturated ketone derivatives. J. Mol. Struct. 2020, 1206, 127755. 10.1016/j.molstruc.2020.127755. [DOI] [Google Scholar]
  46. Khan B.; Khalid M.; Shah M. R.; Tahir M. N.; Khan M. U.; Ali A.; Muhammad S. Efficient Synthesis by Mono-Carboxy Methylation of 4,4′-Biphenol, X-ray Diffraction, Spectroscopic Characterization and Computational Study of the Crystal Packing of Ethyl 2-((4′-hydroxy-[1,1′-biphenyl]-4-yl)oxy)acetate. ChemistrySelect 2019, 4, 9274–9284. 10.1002/slct.201901422. [DOI] [Google Scholar]
  47. Tariq S.; Raza A. R.; Khalid M.; Rubab S. L.; Khan M. U.; Ali A.; Tahir M. N.; Braga A. A. C. Synthesis and structural analysis of novel indole derivatives by XRD, spectroscopic and DFT studies. J. Mol. Struct. 2020, 1203, 127438. 10.1016/j.molstruc.2019.127438. [DOI] [Google Scholar]
  48. Hussain A.; Khan M. U.; Ibrahim M.; Khalid M.; Ali A.; Hussain S.; Saleem M.; Ahmad N.; Muhammad S.; Al-Sehemi A. G.; Sultan A. Structural parameters, electronic, linear and nonlinear optical exploration of thiopyrimidine derivatives: A comparison between DFT/TDDFT and experimental study. J. Mol. Struct. 2020, 1201, 127183. 10.1016/j.molstruc.2019.127183. [DOI] [Google Scholar]
  49. Fukui K. Role of frontier orbitals in chemical reactions. Science 1982, 218, 747–754. 10.1126/science.218.4574.747. [DOI] [PubMed] [Google Scholar]
  50. Parr R. G.; Donnelly R. A.; Levy M.; Palke W. E. Electronegativity: the density functional viewpoint. J. Chem. Phys. 1978, 68, 3801–3807. 10.1063/1.436185. [DOI] [Google Scholar]
  51. Parr R. G.; Pearson R. G. Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 1983, 105, 7512–7516. 10.1021/ja00364a005. [DOI] [Google Scholar]
  52. Lesar A.; Milošev I. Density functional study of the corrosion inhibition properties of 1, 2, 4-triazole and its amino derivatives. Chem. Phys. Lett. 2009, 483, 198–203. 10.1016/j.cplett.2009.10.082. [DOI] [Google Scholar]
  53. Chattaraj P. K.; Giri S.; Duley S.; et al. Chem. Rev. 2011, 111, PR43–PR75. 10.1021/cr100149p. [DOI] [PubMed] [Google Scholar]
  54. Parr R. G.; Szentpály L. v.; Liu S. Electrophilicity Index. J. Am. Chem. Soc. 1999, 121, 1922–1924. 10.1021/ja983494x. [DOI] [Google Scholar]
  55. Koopmans T. Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den einzelnen Elektronen eines Atoms. Physica 1934, 1, 104–113. 10.1016/S0031-8914(34)90011-2. [DOI] [Google Scholar]
  56. Sert Y.; Sreenivasa S.; Doǧan H.; Mohan N. R.; Suchetan P. A.; Ucun F. Vibrational frequency analysis, FT-IR and Laser-Raman spectra, DFT studies on ethyl (2E)-2-cyano-3-(4-methoxyphenyl)-acrylate. Spectrocrim. Acta, A. 2014, 130, 96–104. 10.1016/j.saa.2014.03.061. [DOI] [PubMed] [Google Scholar]
  57. Parr R. G.; Yang W.. International series of monographs on chemistry 16: Density-functional theory of atoms and molecules; Oxford University Press: New York, 1989. [Google Scholar]
  58. Lawal M. M.; Govender T.; Maguire G. E.; Kruger H. G.; Honarparvar B. Idefined chemical concepts: the problem of quantification. Int. J. Quantum Chem. 2017, 118, e25497. [Google Scholar]
  59. Murugavel S.; Velan V. V.; Kannan D.; Bakthadoss M. Synthesis, crystal structure analysis, spectral investigations, DFT computations, Biological activities and molecular docking of methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene) sulfonamido] methyl}-3-(4-fluorophenyl) prop-2-enoate, a potential bioactive agent. J. Mol. Struct. 2016, 1108, 150–167. 10.1016/j.molstruc.2015.11.047. [DOI] [Google Scholar]
  60. Sun Y.-X.; Hao Q.-L.; Wei W.-X.; Yu Z.-X.; Lu L.-D.; Wang X.; Wang Y.-S. Experimental and density functional studies on 4-(3, 4-dihydroxybenzylideneamino) antipyrine, and 4-(2, 3, 4-trihydroxybenzylideneamino) antipyrine. J. Mol. Struct. 2009, 904, 74–82. 10.1016/j.theochem.2009.02.036. [DOI] [Google Scholar]
  61. Murugavel S.; Velan V. V.; Kannan D.; Bakthadoss M. Experimental and computational approaches of a novel methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene) sulfonamido] methyl}-3-(4-chlorophenyl) prop-2-enoate: A potential antimicrobial agent and an inhibition of penicillin-binding protein. J. Mol. Struct. 2016, 1115, 33–54. 10.1016/j.molstruc.2016.02.084. [DOI] [Google Scholar]
  62. Geskin V. M.; Lambert C.; Brédas J.-L. Origin of high second-and third-order nonlinear optical response in ammonio/borato diphenylpolyene zwitterions: the remarkable role of polarized aromatic groups. J. Am. Chem. Soc. 2003, 125, 15651–15658. 10.1021/ja035862p. [DOI] [PubMed] [Google Scholar]
  63. Peng Z.; Yu L. Second-order nonlinear optical polyimide with high-temperature stability. Macromolecules 1994, 27, 2638–2640. 10.1021/ma00087a039. [DOI] [Google Scholar]
  64. Breitung E. M.; Shu C.-F.; McMahon R. J. Thiazole and thiophene analogues of donor– acceptor stilbenes: molecular hyperpolarizabilities and structure– property relationships. J. Am. Chem. Soc. 2000, 122, 1154–1160. 10.1021/ja9930364. [DOI] [Google Scholar]
  65. Tsutsumi N.; Morishima M.; Sakai W. Nonlinear optical (NLO) polymers. 3. NLO polyimide with dipole moments aligned transverse to the imide linkage. Macromolecules 1998, 31, 7764–7769. 10.1021/ma9803436. [DOI] [Google Scholar]
  66. Balachandran V.; Lakshmi A.; Janaki A. Vibrational spectroscopic studies and natural bond orbital analysis of 4, 6-dichloro-2-(methylthio) pyrimidine based on density functional theory. Spectrochim. Acta, A 2011, 81, 1–7. 10.1016/j.saa.2011.02.011. [DOI] [PubMed] [Google Scholar]
  67. Williams D. J.; Prasad P.. Introduction to nonlinear optical effects in molecules and polymers; Wiley: New York, 1990. [Google Scholar]

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