Synthesis, antibacterial and computational studies of Halo Chalcone hybrids from 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one

https://doi.org/10.1016/j.jics.2021.100051Get rights and content

Highlights

  • Synthesis and Characterisation of Halo containing Chalcones.

  • Valuable insights into Molecular properties of six synthesized Chalcones.

  • HOMO-LOMO energy difference and descriptors of Chemical reactivity are predicted.

  • Electronic and Vibrational Properties were analyzed Experimentally and Theoretically.

  • Antimicrobial studies.

Abstract

In an endeavor to develop antibacterial agents, a series of six 1,4-benzodioxan-6-yl substituted chalcone derivatives were synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one with fluoro and chloro substituted aromatic aldehydes. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR spectroscopic techniques. The density functional theory (DFT) calculations were performed using the B3LYP functional with the 6-31G(d,p) basis set for the optimization of molecular geometries and frequency calculations. The CAM-B3LYP functional with a 6-31G(d,p) basis set was used in time-dependent density functional theory (TD-DFT) calculations for the electronic absorption studies. Optimized geometries, frontier molecular orbitals, and global reactivity descriptors' specifications were computed and addressed. The simulated electronic absorption spectra were recorded in the gas phase and dichloromethane (DCM) solvent. The electronic configurations, oscillator strengths, and excited state energies were also discussed. The theoretical UV–Vis and IR vibrational analyses were equated with the experimental findings for the assignment of absorption bands. The synthesized chalcones were evaluated for in vitro antibacterial activities against two Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram negative bacteria (Escherichia coli and Proteus vulgaris). The DFT simulations were correlated with the antibacterial findings and it was discovered that they were highly helpful in the designing antibacterial agents and to establish the structure–activity relationship. Theoretical calculations are in good correlation with the in vitro antibacterial results.

Introduction

Due to the excellent pharmacological exercises, the chalcones of both natural and synthetic origin have received ample attention. Continuing through the worldwide reports in every database of various recorded and awarded patents of medicinal interest, an exceedingly strong understanding is that the researchers have deeply tried to transform the concealed natural and traditional pharmacological information into advanced medications. The rapid increase in antibiotic resistance has become a notorious global epidemic, and chalcone derivatives have been seen as one of the sets of compounds that fascinate this serious public health issue for the advancement of pharmaceuticals [[1], [2], [3]]. Chalcones belong to a class of flavonoids and are widely distributed in plants such as fruits, vegetables, tea, and spices [[4], [5], [6]]. Natural and synthetic forms of chalcones are found to show various important bioactivities including anticancer [7], antimicrobial [8], antioxidant [9], anti-inflammatory [10], antitubercular [11], anti-angiogenic [12], anti-breast cancer [13]. In view of its appreciative antimicrobial activity, the chalcone framework has been utilized for chemical alteration to discover novel derivatives with improved pharmacological profiles. The majority of the chalcone moieties have produced profound interest owing to the fact that their biological properties and characteristic conjugated molecular framework and subsequently are in the focal point of consideration of drug designing. Chalcones are natural biocides and are notable intermediates in the synthesis of different heterocyclic scaffolds [14,15].

Chalcone compounds have a typical 1,3-diaryl-2-propen-1-one chemical skeleton, also known as chalconoid, which occurs as trans and cis isomers, with a thermodynamically more stable trans isomer. For clinical use, many chalcone-based compounds have been endorsed. Metochalcone, for example, was introduced as a choleretic treatment, while sofalcone was previously seen as an anti-ulcer and mucoprotective drug [[16], [17], [18]]. Conventionally chalcones can be synthesized by Claisen-Schmidt condensation; the condensation reaction between aromatic aldehydes and aromatic ketones to form α,β-unsaturated aromatic enone pharmacophore. The presence of α,β-unsaturated keto function in chalcones can undergo conjugate addition into an essential protein with a nucleophilic group, thereby conferring antimicrobial activity. Chalcones containing heterocyclic ring systems of nitrogen, oxygen, or sulphur have improved pharmacological activity. With the widespread benefits of halogenated organic compounds bearing heterocyclic ring system, we have directed our investigation in the synthesis of chalcone derivatives adhered to a heterocyclic ring containing an oxygen atom.

The field of DFT has captivated researchers because of its wide applications in structural chemistry. Utilizing DFT, several noteworthy structural parameters could be speculated [[19], [20], [21]]. The molecular properties like molecular structure, bond lengths, and bond angles and spectroscopic properties like UV–Vis, FT-IR, Raman, and NMR have been largely explored by using the DFT method with appropriate functional and basis set [[22], [23], [24], [25]]. It has been reported that the DFT approach using B3LYP functional with suitable basis set predicts the UV–Vis and vibrational spectroscopic properties in right agreement with the experimental spectroscopic data [[26], [27], [28], [29], [30], [31]]. The assignment of absorption bands and, as a result, the prediction of electronic and chemical properties of molecules are observed to be appropriate using the B3LYP functional with a 6-31G(d,p) basis set [[32], [33], [34], [35], [36]]. DFT has been used to research these obligatory facets in the computational study of synthesized molecules. Most notably, DFT simulations have previously been used to anticipate biological activities [[37], [38], [39]]. By considering all these important aspects of biologically active chalcones and computational chemistry we present here the combined study on synthesis, antibacterial and computational investigation of chloro and fluoro bearing chalcones derived from 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one. In the context of the study, this is the first report on the combined exploration of antibacterial and DFT studies of the synthesized chalcones.

Section snippets

Chemistry

All the chalcone derivatives synthesized (3a–3f) via the Claisen–Schmidt condensation reaction were characterized by FT-IR, 13C NMR, and 1H NMR spectroscopy, and the findings were correlated with literature data. The structures of the synthesized chalcones are given in Table 1 and their abbreviations are used for the discussion of data presented in the current research work. For compound DBDCPP-3 containing 2,6-dichlorobenzaldehyde moiety, the highest yield (95%) was obtained, whereas compound

Conclusions

In conclusion, this work reports the synthesis, computational and antibacterial studies of six chalcone derivatives derived from 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one. The synthesized compounds were obtained in good to excellent yields. The structures were affirmed using FT-IR and NMR spectral analysis. The 1HNMR study revealed a trans configuration for the olefinic double bond. The B3LYP functional with 6–31G(d,p) basis set was used to perform DFT calculations for the optimization

General remarks

The chemicals (Make-SD fine chemicals and Avra synthesis) with high purity were purchased from the Sigma laboratory, Nashik, and were utilized accordingly. On the Shimadzu spectrometer, the FT-IR spectra of the synthesized compounds were recorded using a KBr disc technique. The NMR analysis was performed on advanced multinuclear FT-NMR Spectrometer model. In chloroform-d, the compounds were dissolved. Chemical shifts were recorded in ppm using tetramethylsilane (TMS) as an internal standard.

Compliance with ethical standards

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Authors acknowledge central instrumentation facility, Savitribai Phule Pune University, Pune for NMR and CIC, KTHM College, Nashik for FT-IR spectral analysis. Authors would also like to thank Arts, Science and Commerce College, Manmad for permission and providing necessary research facilities. Authors would like to express their sincere and humble appreciation to Prof. (Dr.) Arun B. Sawant for Gaussian study. Prof. Mahesh Patil is gratefully acknowledged for the antibacterial studies. Dr.

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