4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid, a newly synthesized amide with hydrophilic and hydrophobic segments: Spectroscopic characterization and investigation of its reactive properties

J. Serb. Chem. Soc. 83 (1) 1–18 (2018) JSCS–5054 UDC 547.572.3–304.2+547.261’451.64: 544.431.143:541.124.7+519.677 Original scientific paper 4-[(4-Acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid, a newly synthesized amide with hydrophilic and hydrophobic segments: Spectroscopic characterization and investigation of its reactive properties SHEENA Y. MARY1, EBTEHAL S. AL-ABDULLAH2, HAYA I. ALJOHAR2, BADIADKA NARAYANA3, PRAKASH S. NAYAK3, BALADKA K. SAROJINI4, STEVAN ARMAKOVIĆ5, SANJA J. ARMAKOVIĆ6#, CHRISTIAN VAN ALSENOY7 and ALI A. EL-EMAM2* 1Department of Physics, Fatima Mata National College, Kollam, Kerala, India, 2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia, 3Department of Studies in Chemistry, Mangalore University, Mangalagangothri, Mangalore 574199, India, 4Department of Studies in Industrial Chemistry, Mangalore University, Mangalagangothri, Mangalore 574199, India, 5University of Novi Sad, Faculty of Sciences, Department of Physics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia, 6University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad, Serbia and 7Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020, Antwerp, Belgium (Received 3 January, revised 17 March, accepted 16 May 2017) Abstract: The FT-IR and FT-Raman spectra of 4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid were recorded. The vibrational wave numbers were computed by DFT quantum chemical calculations and the vibrational assignments were realized using the potential energy distribution. The theoretically predicted geometrical parameters were in agreement with the XRD data. Determination and visualization of molecule sites prone to electrophilic attacks were performed by mapping the average local ionization energies (ALIE) to the electron density surface. Furthermore, determination of possible reactive centres of title molecule was realized by calculation of the Fukui functions. Intramolecular non-covalent interactions were also determined and visualized. In addition, prediction of molecule sites possibly prone to autoxidation was performed by calculation of the bond dissociation energies (BDE), while the stability of the title molecule in water was assessed by calculation of radial distribution functions (RDF) obtained after molecular dynamics (MD) simulations. * Corresponding author. E-mail: # Serbian Chemical Society member. https://doi.org/10.2298/JSC170103056M 1 Available on line at www.shd.org.rs/JSCS/ ________________________________________________________________________________________________________________________ (CC) 2018 SCS. 2 MARY et al. The docked title ligand compound forms a stable complex with insulin receptor kinase and gives a binding affinity of –10.2 kcal* mol-1. Keywords: DFT; ALIE; BDE; RDF; molecular docking. INTRODUCTION Copolymers containing both hydrophilic and hydrophobic segments are drawing considerable attention because of their possible use in biological systems. N-Substituted itaconamic acids are strongly amphiphilic molecules.1 Itaconic anhydride is an unsaturated organic dicarbonic anhydride with one carbonyl group conjugated to the methylene group and can be regarded as a substituted acrylic or methacrylic derivative and it can be obtained from renewable resources.2 Itaconic anhydride derivatives are useful for the synthesis of various biodynamic derivatives such as imides, oxazepine and oxobutanoic acid.3–6 Amide bonds, which play major roles in the elaboration and composition of biological systems, are the main bonds that link amino acid building blocks together to give proteins and these types of bonds are not limited to biological systems and are indeed present in a huge array of molecules including major marketed drugs. Amide derivatives were reported to possess anti-inflammatory,7–9 antitubercular,10,11 and anti-proliferative12 activities. Due to highly frequent use and improper disposal, pharmaceutical molecules significantly accumulate in all types of waters and exhibit harmful effects towards aquatic organisms.13,14 Additionally, these molecules are synthesized to be very stable and thus their removal is very difficult under natural conditions, while simultaneously, conventional procedures for their removal from water are not efficient.15,16 For the removal of pharmaceutical molecules from water, scientists have developed forced degradation procedures based on advanced oxidation processes.14,15,17–21 These efforts are tedious and time consuming and there is constant need for rationalization and optimization of these procedures. In this regard, DFT calculations and molecular dynamics (MD) simulations have been readily employed,22–25 since they are valuable for the prediction of the reactive properties of investigated molecules by relatively inexpensive computational experiments. Information on local reactivity properties obtained by molecular modelling principles is also valuable for the determination and validation of degradation mechanisms.15 In this work, a complete vibrational spectroscopic analysis of 4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid was performed by combining experimental and quantum chemical calculations, including molecular dynamics simulations. EXPERIMENTAL The title compound (C13H13NO4) was prepared in 87 % yield via the reaction of 3-methylidenedihydrofuran-2,5-dione with 4′-aminoacetophenone at room temperature as previously described.26 * 1 kcal = 4184 J Available on line at www.shd.org.rs/JSCS/ ________________________________________________________________________________________________________________________ (CC) 2018 SCS. SPECTROSCOPY OF 4-[(4-ACETYLPHENYL)AMINO]-2-METHYLIDENE-4-OXOBUTANOIC ACID AND REACTIVE PROPERTIES 3 The FT-IR spectrum of the title compound was recorded using KBr pellets on a DR/ /Jasco FT-IR spectrometer. The FT-Raman spectrum was obtained on a Bruker RFS 100/s instrument. Quantum chemical calculations The quantum chemical calculations of the title compound were performed with the Gaussian’09 program,27 using the B3LYP/6-311++G(d) (5D, 7F) basis set to predict the molecular structure and frequencies. A scaling factor of 0.9613 had to be used to obtain a considerably better agreement with the experimental data.28 The structural parameters with XRD data corresponding to the optimized geometry of the title compound (Fig. 1) are given in Table S-I of the Supplementary material to this paper. The assignments of the calculated frequencies were realized using Gaussview29 and GAR2PED30 software. Fig. 1. Optimized geometry of 4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid. The Jaguar 9.0 program31 was used for the DFT calculations and the Desmond program32-34 was used for the MD simulations, both as implemented in the Schrödinger Materials Science Suite 2015-4. The B3LYP exc (...truncated)