INTRODUCTION

Sulfonamides together with various pharmacological agents with antibacterial, anti-carbonic anhydrase, diuretic, and hypoglycemic activities constitute a significant group of drugs. With the progressivity in the technology and analysis techniques, considerable influences of sulfonamides in living tissue have been elucidated. Sulfonamide and its derivatives have multifunctional chemistry and so interests are increasing has been made to synthesize the new Schiff base ligands and its complexes. [1]. The enzyme, which has the strongest inhibitory effect of sulfonamides, is known as carbonic anhydrase (CA). This enzyme is found in plants, animals and humans; it catalyzes the conversion of carbonic acid to carbon dioxide. Numerous studies have been conducted on the inhibition of carbonic anhydrase enzyme and the treatment of diseases such as diuretic, glaucoma, epilepsy, acute mountain sickness and obesity and cancer in recent years [2–8]. Additionally, Schiff bases and complexes from commercial drugs of sulfamethoxazole and sulfoxazoline have been investigated in terms of biological activity in many studies.

In our previous papers, different sulfonamides were synthesized and antimicrobial activities of the compounds were investigated [9–12]. Moreover, structural and spectroscopic properties of methanesulfonic acid hydrazide, [13] methanesulfonic acid 1-methylhydrazide [14] and some methanesulfonylhydrazone derivatives were also studied with the conformation analysis of them [15, 16]. In this paper, two new Schiff bases compound have been synthesized since the above-mentioned importance. Synthesized compounds were named as (2E)-2-[4-(dimethylamino)phenyl]-2-({4‑[(4-methanediidyl-5-methyl-2H-1λ3,2-oxazol-2-id-3-yl)sulfamoyl]phenyl}imino)ethane-1,1-diide (L1) and (2E)-2-({4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl}imino)-2-[4-(dimethylamino)phenyl]ethane-1,1-diide (L2). They were derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehyde. Synthesized compounds have been characterized by using elemental analyses, FT-IR and 1H–13C NMR methods. The theoretical vibrational modes and nonlinear optical (NLO) activity have been investigated by B3LYP/6-311G(d,p) level of theory. 1H and 13C NMR calculations of      the      compounds were performed with GIAO/DFT/B3LYP/6-311G(d,p) methods in CDCl3.

EXPERIMENTAL

Synthesis and Spectroscopic Measurements of the Compounds

The general method of synthesis of Schiff bases is as follows. To a solution of 4-dimethylaminobenzaldehyde in 20 mL super dry ethanol sulfisoxazole/sulfamethoxazole was added and was stirred at room temperature for 15 min followed by reflux for 24 h. Yellow-orange precipitate appeared and was filtered, washed with ethanol (3 × 15 mL). The product was dried and crystallized from ethanol at. For both of the compounds, experimental mid-IR spectra were recorded on Perkin Elmer Spectrum 100 FT-IR spectrometer with ATR (Attenuated total reflection) equipment at 4000–400 cm–1 region. The C, H, N, and S analyses of the compounds were done on a LECO CHNS 9320 analyzer. Elemental analysis results are presented in Table 1.

Table 1.   The C, H, N, and S analyses of the compounds
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COMPUTATIONAL METHOD

The molecular geometry optimizations, nonlinear optical (NLO) activity and vibrational modes were computed by with the help of the Gaussian 09 [17] and Gaussview [18] visualization program. The 6-311G(d,p) basis set was used for the all calculations. The geometries were fully optimized without any constraint with the help of an analytical gradient procedure implemented within the Gaussian 09. The molecular structures of the compounds were given in Fig. 1. Vibrational modes and NLO activity were calculated using optimized structures. The fundamental vibrational modes were characterized by their PED (potential energy distribution) obtained by using the VEDA4 program [19]. The calculated frequencies were scaled by 0.9668 to correct the differences between the recorded and calculated data. In the calculation to 1H and 13C NMR chemical shifts in CDCl3, the GIAO method was used.

Fig. 1.
figure 1

The molecular structures of L1 and L2 in vacuum.

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RESULTS AND DISCUSSIONS

Conformational Analysis of the Compounds

In this study, the synthesized compounds are conformationally non-rigid molecules with internal rotation. In this case, these molecules can exist in the form of several conformers and so it is necessary to describe the conformational composition of the compounds. In Fig. 2, it is seen four stable conformers of L1 and L2. The total energy calculated for the most stable structure of L1 is –1579.1352 Hartree. For the most stable structure of L2, the total molecular energy was calculated as –1618.4549 H. The energy differences calculated for each of the conformations are given in Fig. 2 as kcal/mol. For L1, the energy differences between the conformations have been calculated as 2.53, 2.55, and 4.22 kcal/mol, respectively, for L2, as 1.87, 1.88, and 2.88 kcal/mol. The energies of the second and third conformers are quite close to each other. All calculations and investigations in the following sections of the paper are made for the most stable versions.

Fig. 2.
figure 2

Conformational structures and energy differences of L1 and L2 in vacuum.

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Vibrational Modes of the Compounds

L1 molecule has 47 atoms and 135 vibrational modes, L2 has 50 atoms and 144 vibrational modes. They belongs to the point group C1. Experimental and simulated mid-IR spectra of the compounds were given in Figs. 2 and 3. The selected some important experimental and theoretical vibrational frequencies and IR intensities of the compounds were also given in Tables 2 and 3 together the with PED % assignments.

Fig. 3.
figure 3

(a, с) Experimental and (b, d) calculated mid-IR spectra of L1 (a, b) and of L2 (с, d).

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Table 2.   Selected experimental and calculated vibrational modes of L1 (ν, cm–1)
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Table 3.   Selected experimental and calculated vibrational modes of L2 (ν, cm–1)
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It is seen from Table 1 that both structures have N‒H stretching modes. These vibrations were observed at 3282vw for L1 and calculated at 3432 cm–1. For L2, it was recorded at 3382 cm–1 and calculated at 3454 cm–1. The main reason for the differences between the calculated and experimental results for both structures is that the calculations are made for a single molecule isolated in the gas phase but the experimental measurements are made in the solid phase and there are too many intermolecular interactions [20].

C–H stretching modes were observed between 2860–3150 cm–1 in experimental IR spectra for both structures and these modes were calculated between 2890–3156 cm–1 in accordance with experimental results. C–C and C=C stretching vibrations were calculated in the range of 1530–1627 cm–1. These modes are in the range of 1530–1650 cm–1 in the experimental spectra. In the literature, these bands are observed between 1400 and 1625 cm–1 [21]. These modes are supported by the literature. In previous studies performed, S–O stretching modes have been shown in the range of 1100–1150 cm–1 [22]. In this study, while the S–O stretching mode of L1 was calculated as two bands in 1117 and 1126 cm–1, this mode was calculated as overlapped in 1262 cm–1 for L2. We think that the reason for differences between calculated modes for the two structures is that the placement and position of the isoxazole ring of L2 are different from that of L1. Because of this position difference, intermolecular interactions are different for both samples and there are serious differences between the vibration modes. The other important stretching vibrational modes are the N–C stretchings. N–C stretching modes for L1 were calculated alone at 1627 and 1340 cm–1. In addition, they were calculated at 1600, 1510, and 1486 cm–1 in combination with C–C and H–C–C vibrations. In the experimental spectrum, respectively, 1615w, 1333m, 1602w, 1509m, and 1492m were labeled. L2 for, these modes were calculated alone at 1344 cm–1 and were calculated at 1627, 1562 cm–1 with the combinations of C–C. These bands were observed at 1336s, 1650m, and 1578m in the experimental spectrum. It is also seen from the table that all of the stretching, bending and torsional modes calculated are good agreement with experimental results.

NMR Studies

The NMR spectra (1H–13C) of L1 and L2 were measured and interpreted in DMSO. Theoretical NMR calculations were performed with B3LYP/6-311G(d,p) level of theory in DMSO phase. Isotropic shielding tensors of 13C were changed into chemical shifts by using a linear relationship suggested by Blanco et al. [23]. A similar relationship proposed by Silva et al. [24] was used to obtain chemical shifts for 1H. The computed chemical shift values fit well with experimental values. The experimental and calculated chemical shift values are shown in Table 4. The 13C NMR and 1H NMR spectrums of the Schiff bases in DMSO are given in Fig. 4.

Table 4.   The experimental and theoretical 1H and13C NMR chemical shifts (δ, ppm) for ligands
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Fig. 4.
figure 4

(a, с) 1H NMR of L1 (a), L2 (c); (b, d) 13C NMR of L1 (b), L2 (d).

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In the 1H NMR spectrum of L1; H1, H4, H12, and N(CH3)2 protons appeared at 1.63, 1.04, 8.41, and 3.83–2.95 ppm were calculated at 1.77, 1.07, 8.78, and 3.64–2.76 ppm. A signal were also observed at δ = 9.65 ppm of the N–H-group (calculated at 9.47 ppm). Signals in the range of δ = 6.26–7.75 ppm region belong to aromatic Ar–H protons. In 13C-NMR spectra of L1; C1, C4, C12, and N(CH3)2 carbon signals are assigned at 10.76, 6.26, 190.30, and 19.00 ppm (calculated 10.90, 6.11, 190.44, and 19.22 ppm), respectively. Signals in the range of δ = 104.70–162.36 ppm region belong to aromatic Ar–C carbons.

In the 1H NMR spectrum of L2; H1, H12, and N(CH3)2 protons appeared at 2.28, 8.38, and 3.02–2.89 ppm were calculated at 2.19, 8.38, and 3.02–2.91 ppm. A signal were also observed at δ = 11.32 ppm of the of the N–H-group (calculated at 10.88 ppm). Signals in the range of δ = 6.06–7.79 ppm region belong to aromatic Ar–H protons. In 13C-NMR spectra of L2; C1, C12, and N(CH3)2 carbon signals are assigned at 10.56, 190.30, and 12.48 ppm (calculated 10.67, 191.27, and 12.78 ppm), respectively. Signals in the range of δ = 95.73–162.75 ppm region belong to aromatic Ar–C carbons.

Nonlinear Optical Properties (NLO)

The optical properties of matter can be expressed as the response of the electrons to the electric field. As it is known, the electric field component of the light sent to the material poles that substance. The polarity of an atom or molecule is a measure of how easily the nucleus and electrons can shift from their equilibrium states. The reaction of an isolated molecule against an applied external electric field results in a reshaping of the dipole moment of the molecule:

$${{\mu }_{t}} = {{\mu }_{0}} + {{\alpha }_{{ij}}}{{E}_{i}} + {{\beta }_{{ijk}}}{{E}_{i}}{{E}_{j}} + \ldots ,$$
((1))

where μ is called the permanent dipole moment of the molecule, α is the linear polarizability, βijk is first order hyperpolarizability tensor components. First order hyperpolarizability is quantities that affect the nonlinear optical performance of matter. The mean polarizability 〈α〉 is defined as [25]:

$$\left\langle \alpha \right\rangle = 1{\text{/}}3({{\alpha }_{{xx}}} + {{\alpha }_{{yy}}} + {{\alpha }_{{zz}}}).$$

The calculation of first order hyperpolarizability from output given as follows [26]:

$$\begin{gathered} {{\beta }_{{{\text{tot}}}}} = [{{({{\beta }_{{xxx}}} + {{\beta }_{{xyy}}} + {{\beta }_{{xzz}}})}^{2}} + {{({{\beta }_{{yyy}}} + {{\beta }_{{yzz}}} + {{\beta }_{{yxx}}})}^{2}} \\ + \;{{({{\beta }_{{zzz}}} + {{\beta }_{{zxx}}} + {{\beta }_{{zyy}}})}^{2}}{{]}^{{1/2}}}. \\ \end{gathered} $$
((3))

The calculated dipole moment μ, mean polarizability 〈α〉, first order hyperpolarizability βtot are reported in the Table 5.

Table 5.   The electric dipole moment (μ, D), the mean polarizability (〈α〉 × 1024, esu) and the first hyperpolarizability (βtot × 1033, esu) of L1 and L2
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First order hyperpolarizability of L1 and L2 was computed to be 75.23 × 10–30 and 42.18 × 10–30 esu, respectively. Urea is reference molecule for classification of good NLO organic molecules. It found that, the first order hyperpolarizabilities of L1 and L2 are 201.79 and 113.14 times larger than that of urea (0.3728 × 10–30 esu), respectively. According to evaluated results, the L1 and L2 present large nonlinear optical activity and are candidate molecules for nonlinear optical applications.

CONCLUSION

As a result of this study, the following decisions were obtained. Two new Schiff bases compounds L1 and L2 were synthesized and their structures were elucidated using elemental analysis and spectroscopic methods. Estimated structures of synthesized compounds were drawn in 3D and optimizations were performed. Based on optimized structures, theoretical vibrational modes, 1H and 13C NMR and NLO calculations were done. The all calculated parameters were compared with the experimental ones and the structures of the compounds have clarified. Intermolecular hydrogen bond interactions causes serious differences between calculated and experimental N–H stretching vibrational modes. The first order hyperpolarizabilities of L1 and L2 are 201.79 and 113.14 times larger than that of urea (0.3728 × 10–30 esu). The compounds present large nonlinear optical activity.