Research Article
Experimental and theoretical spectroscopic studies in relation to molecular structure investigation of para chloro, para fluoro and para nitro maleanilinic acids

https://doi.org/10.1016/j.compbiolchem.2018.08.006Get rights and content

Highlights

  • This research deals with preparation and structure characterization of three novel maleanilic acid derivatives.

  • Their structures had been characterized by Elemental, FT-IR, Raman XRD and Thermal Analyses.

  • These practical data are compared and confirmed at DFT/B3LYP/6-311++G(d,p) level of theory.

  • Their biological activities and Cytoxicity against cancer cells were performed.

Abstract

In the present work novel para chloro, para fluoro and para nitro maleanilic acid derivatives were prepared and investigated using FT-IR, thermal analyses (TA) measurements (TGA/DTG and DTA) in comparison with mass spectral (MS) fragmentation at 70 eV. The crystallographic structures of studied compounds were investigated by X-ray diffraction (XRD). The vibrational frequencies and the corresponding normal modes were evaluated at the optimized geometry. Vibrational modes were analyzed using GAUSSVIEW software. Experimental FT-IR and Raman spectra of the three newly prepared derivatives, namely, (E) – oxo -4- ((4- nitro phenyl) amino)-4- oxobut-2-enoic acid (p-NMA), (E) -4- ((4- chloro phenyl)amino)-4- oxobut -2- enoic acid (p-ClMA), (E) -4- ((4- fluoro phenyl) amino)- 4- oxobut -2- enoic acid (p-FMA) were compared with the theoretically calculated one. FT-IR and the observed vibrational frequencies were assigned; thermal analysis and mass spectrum measurements of the maleanilic acid derivatives were recorded and discussed. The computational calculations were carried out by DFT - B3LYP method with 6-311++G(d,p) basis sets and the corresponding results were tabulated. The alternations of structures of p-FMA, p-ClMA and p-NMA due to the subsequent substitutions were investigated. This correlation between experimental and theoretical calculations provided a good confirmation of the proposed structures of the newly prepared compounds. The derivatives were found to be highly effective against Hepatocellular carcinoma cells > Breast carcinoma cells > colon carcinoma cells. It was recognized, that cancer cells over expression promotes tumorigenic functions; can be suppressed by p-NMA > p-FMA > p-ClMA inhibitors.

Graphical abstract

Graphical correlation between HOMO and LUMO values three derivatives-maleanilic acid molecules calculated at DFT/B3LYP/6-311++G(d,p) level of theory

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Introduction

Many publications regarding the synthesis of maleanilic acids using equimolar of aniline or its derivatives with maleic anhydride in the presence of solvents were performed (Cava et al., 1961; Khan et al., 2009; Gowda and Mahendra, 2007; Vukovic et al., 1999; Roth, 1978; Ryttel and Makromol, 1999). Different solvents can be used, ether, acetic acid, acetone, nitro benzene, chloroform or mixed solvents such as equal volume of ethyl alcohol and water. N-substituted maleanilic acid derivatives can be used to prepare the maleimides, which are an important class of substrates for biological as chemical probes of protein structure (Corrie, 1994). It can be used as protective and curative fungicides (Fujinami et al., 1972). In polymer chemistry they can be used as photo initiators for free-radical polymerization (Body et al., 2006; Griffiths et al., 1981; Morder, 1987; Rich et al., 1975; Keller and Rudinger, 1975; Nath et al., 2001; Gielen, 2002; Chandrasekhar et al., 2002). They can also be used as monomers in poly-maleimides or their copolymers synthesis. The computational chemistry (Mulholland and Dundas, 2018) is rapidly growing using home computers and getting faster; which can be used for the interpretation of experimental results (Mura et al., 2002). Therefore this paper is mainly focused on studying molecular structure- reactivity relationship of maleanilic acid- derivatives via investigation of their decomposition mechanisms using thermal (TA) in comparison with the theoretical molecular orbital calculations. Thermogravimetric (TG/DTG) analysis is used to provide quantitative information on weight losses due to decomposition as a function of time and temperature. This work involved structure studies of halogen and nitrogen N-substituted maleanilinic acid by spectroscopic techniqes, also included a correlation between, mass spectral fragmentation and thermal analysis degradation of the selected derivatives. The experimental results obtained are also correlated with the theoretical data of MOCS to identify the weakest bonds broken during both mass and thermal studies. Knowing this structural session of bonds can be used to decide the active sites of this derivative responsible for its chemical and biological properties.

Section snippets

Materials and procedures

All chemicals were purchased from Arcos, Oxford and Merck Chemical Co. (Germany). Maleic anhydride, p-Fluoroaniline, p-Chloroaniline and p-Nitroaniline were used as received. Three N-maleanilic acids were prepared according to the procedures reported in the literature (Saedi, 2013). Aniline derivative of 12.75 g (0. 1 mol) was mixed and ground at room temperature with maleic anhydride 9.8 g (0. 1 mol) in an agate mortar. During crunching processes greenish-yellow color products appeared. The

Elemental analyses (EA) of N-substituted maleanilic acids

A series of three n-substituted Maleanilinic acid derivatives (I-III) were prepared by reaction between solid maleic anhydride (MA) and various solid N-substituted anilines at room temperature by solvent-less procedure. The prepared Maleanilinic acids are depicted in Scheme 1 . The synthetic method used to prepare the series is simple, clean, economic and nearly quantitative of high yields (Table 1).

The elemental analysis of the prepared compounds and their analytical parameters are given in

Conclusion

In the present investigation, these derivatives have always been of great interest; because of their importance and anticancer activities and method for their preparation is simple, clean, economic and nearly quantative or high yield. FT-IR and Raman spectra of the maleanilinic acid p-NMA, p-ClMA and p-FMA are recorded and the observed vibrational frequencies are assigned depending upon their expected region. The variation in Raman reactivity frequencies calculations were compared with FT-IR

Acknowledgments

The authors acknowledge the supports via providing chemicals, wears, instrumental measurements and lab space presented by Ministry of Military production Laboratories and Chemistry Department, Faculty of Science, Cairo University

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