Synthesis, spectroscopic characterization, X-Ray analysis, and DFT-HF calculations of 5-ethoxymethyl-8-hydroxyquinoline

5-EMQ was synthesized according to the method described by Mishra et al. (2005). The obtained product (Scheme 1) was characterized by IR and ¹H, ¹³C NMR methods, the spectral data are shown in Table 1.

Melting points were determined on an automatic electrothermal IA 9200 digital melting point apparatus in capillary Mp: 78–80 °C. ¹H NMR spectra were recorded on a Bruker 300 WB spectrometer at 300 MHz for solutions in Me₂SO-d₆. Chemical shifts are given as δ values with reference to tetramethylsilane (TMS) as internal standard. Infrared spectra were recorded from 400 to 4000 cm⁻¹ on a Bruker IFS 66v Fourier transform spectrometer using KBr pellets. Mass spectrum was recorded on THERMO Electron DSQ II.

High quality powder X-ray diffraction measurements were performed with an Inel CPS120 powder diffractometer (Debye–Scherrer geometry, transmission mode). The sample was introduced into 0.5 mm diameter Lindemann glass capillary. The latter was rotated around its axis in order to minimize preferential orientations of the crystallites and to obtain reflections with exploitable intensities. The time of acquisition was set to 8 h approximately for a good signal-to-nose ratio. Monochromatic Cu-Kα₁ radiation (λ = 1.54056 Å) was selected with asymmetric focusing incident-beam curved quartz monochromator, the generator power was set to 40 kV and 25 mA. The diffracted lines were collected on a 4096 channel detector over an arc of 120° and centered on the sample. External calibration using the Na₂Ca₂Al₂F₁₄ (NAC) cubic phase mixed with silver behenate was performed using cubic spline fittings.

Geometrical data of the molecule in ground state was optimized by density functional theory (DFT) and Hartree–Fock (HF) methods with 6-311G(d,p) basis set, using Gaussian 03 program package at room temperature (Frisch et al. 2004). These methods are more used, actually, to study chemical and biochemical phenomena within a large variety of molecules (Prasad et al. 2013; Li et al. 2014). Because they can reach exactitude similar to other methods as ab initio in less time and less expensive from the computational point of view, on the other hand, they offers similar accuracy for middle sized and large systems.

The chemical structure of the compound deduced from its IR, ¹H, ¹³C and NMR spectra was confirmed by X-ray analysis. Thermal analysis was performed with Perkin-Elmer DSC-7 apparatus using heating rates of 10 K min⁻¹ revealed no solid–solid phase transition between room temperature and the melting point. The melting point temperature (Mp = 351.8 K) was in good agreement with that measured by using digital melting point apparatus (Electrothermal IA 9200) and enthalpy of melting was equal to ∆H = 21.136 kJ/mol.

The crystal structure was determined with materials studio modeling 5.5 (http://​accelrys.​com/​products/​materials-studio). First, the pattern was indexed by means of the peak picking option of the software package and using the X-cell algorithm (Neumann 2003). Then, a Pawley profile-fitting procedure (Pawley 1981) was applied including refined cell parameters, experimental profile fitting with pseudo-Voigt function, zero shift and asymmetry Finger-Cox-Jephcoat function. Distances, angles and torsions in the molecule were obtained via energy-minimization calculations using the Dreiding force field (Mayo et al. 1990). Then, a Monte-Carlo approach was carried out in the direct space to solve the structure (Serbezov et al. 2013) moving the molecule as a rigid-body and allowing the change of the chain torsion angles. Rwp agreement factor of 4.78 % is reached after Rietveld refinement (Rietveld 1969). Describing a good agreement between the measured and calculated spectra for 5-EMQ molecule at 295 K (Fig. 1).

The molecular structure is represented in Fig. 2a. Relevant crystallographic data are summarized in Table 2. The parameters in the CIF form are available as Electronic Supplementary Information from the Cambridge Crystallographic Database Centre (1029560).

The molecule exibited non-planar structure, the dihedral angle calculated between the methylquinolin-8-ol group and other part of the molecule is 77.08° (Fig. 2b).

The stabilized crystal packing is mainly governed by hydrogen bonds (Fig. 3) and π–π stacking interactions (Fig. 4). The intramolecular hydrogen bonds observed in the structure involves the OH functional group, this latter presents strong interactions in many solvents, modify physical properties at room temperature (Kadiri et al. 1994; Cazeau-Dubroca 1991) and enhancing the biological activity of the molecule. Weak intra and intermolecular hydrogen bonds O–H···N and C–H···O types are detected in the structure involving adjacent molecules in different plans, with a gap from 0.638 Å (Fig. 3b). Selected distances (Å) and angles (°) describing the hydrogen bonds are reported in Table 3.

In addition to the hydrogen bond, the crystal packing structure of 5-EMQO shows π–π stacking interactions between 8-quinolinol rings on adjacent molecules (Fig. 4a). Those contacts may stabilize the structure, with ring centroid to ring centroid distance of 3.473 Å (Fig. 4b). This value is similar to the values reported for other π–π interactions (Shi et al. 2007; Zawadzka et al. 2012).

Figure 5a shows an optimized calculated structure of the compound. In Table 4 we report the most optimized structural parameters (bond distances, angles and torsions) obtained from crystal structure data (1), optimized by DFT (B3LYP) (2) and by HF (3), in accordance with the atom numbering scheme given in Fig. 2a. The global minimum energy obtained by DFT and HF structure optimization is calculated as −18244.67 and −18131.48 eV respectively. The dipole moment is equal to 3.0245 Debye.

The C–C bonds lengths optimized with both methods are in a fairly good agreement with the corresponding bond lengths obtained from X-ray analysis, however slight differences on C–C bond lengths may be noticed between DFT(B3LYP) and the HF calculations. The biggest gap between calculation and experience is observed for C(3)–C(4), C(7)–C(8) and C(9)–C(10) bonds at HF method, values are 0.045, 0.056 and 0.050 Å respectively. For the rest of bond lengths type, the highest difference between crystal structure and calculation is observed for the N(1)–C(2) bond with a value of 0.04 and 0.06 Å for DFT and HF methods respectively. Generally the HF method underestimate some bond lengths by Inclusion of the electron correlation which makes this bond shorter because of the increased resonance in the correlated wave function (Arici et al. 2005; Lakshmi et al. 2011; Zawadzka et al. 2015; Kosar and Albayrak 2011). As a result, the DFT method for bond lengths is much closer to experimental data.

The calculated bond angles values obtained with DFT and HF are very similar, but compared to crystal data some discrepancies appears for C(2)–N(1)–C(6) and C(9)C(10)–O(11) with a difference of 5.28° for DFT method and 5.34° for HF method, respectively. Concerning torsion angles, we presented in Table 3 only those with notable discrepancies between X-ray data and the two calculations (DFT and HF) methods. The Azine ring appears a little distorted with smaller C(6)–N(1)–C(2)–C(3), C(2)–N(1)–C(6)–C(5), N(1)–C(2)–C(3)–C(4) torsion angles and bigger C(2)–C(3)–C(4)–C(5), C(3)–C(4)–C(5)–C(6), C(4)–C(5)–C(6)–N(1) torsion angles (Table 4), comparing values from DFT and HF methods to the crystal data. The highest difference corresponds to the C(7)–C(12)–O(13)–C(14) torsion angle with the value of 77.1(13)° in the crystal structure and −178.6° and −178.4° respectively for DFT and HF calculations. The discrepancies between calculated and experimental structural parameters are related to the fact, that calculations refer to the isolated molecule, contrarily experimental results which correspond to interacting molecules in the crystal lattice where intra and intermolecular interactions with the neighboring molecules are present (Kavitha et al. 2010; Ghiasi et al. 2014; Pournamdari et al. 2012).

Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are been computed using B3LYP level 6-311(d,p) of DFT. Figure 5b shows the patterns of the HOMO and LUMO of 5-EMQO. The HOMO–LUMO gap is 4.463 eV. The HOMO energy shows the ability of giving an electron, whereas, the LUMO energy represents the ability of gaining an electron (Pournamdari et al. 2012). In many recent works, the energy gap between HOMO and LUMO has been used to prove the bioactivity from intra molecular charge transfer and to explain the chemical reactivity of the molecule (Fukui 1982; Gunasekaran et al. 2008).

The charge distribution on different atoms (C, N and O) for molecule obtained by using X-ray analysis data B3LYP methods and HF methodes is plotted in Fig. 6. Results obtained by these two methods are similar. This distribution depending on the electronegativity of atoms; the most negative are those present at nitrogen and oxygen atoms. The values obtained from DFT calculations are in fairly agreement with crystal structure. The most negative values are those that are present at nitrogen and oxygen: N1, O11 and O13. It has to be noticed that the carbon atom attached to oxygen and nitrogen atoms: C2, C6, C10, C12 and C14 in both X-ray and B3LYP are electron deficient atoms possessing positive electronic charge due to the oxygen and nitrogen electronegativity . Remaining carbon atoms possess negative electronic charge. Except some discrepancies about C4 and C5 which possess a different electronic charge in DFT calculation, this deviation is probably due to the fact that the intermolecular hydrogen bonding interaction C3–H3–O13 in the crystalline state are dominant influencing the charge distribution in C4 and C5. Furthermore, the DFT calculation refers to the isolated molecule where the intermolecular interactions with the neighboring molecules are absent. This distribution within the molecule and the high dipole moment explain the notable polarization given by the small HOMO-LUMO energy calculated. The molecule will exhibit a significant degree of intramolecular charge transfer from the electron donor section to the electron acceptor section.