Conformational and FTIR analyses of 2,3-dimethoxyphenylboronic acid 2,3-dimetoksifenilboronik asit molekülünün konformasyon ve FTIR analizi

Öz The experimental and theoretical investigations of solvent effect on conformational structure and the hydroxyl stretching vibration of 2,3-dimethoxyphenylboronic acid (2,3-dmpba; C6H3(OCH3)2B(OH)2) molecule were studied by Fourier transform infrared (FTIR) spectroscopy and density functional theory (DFT). Calculations were performed by four conformational isomers of the title compound in eighteen different organic solvents by the polarizable continuum model (PCM). Scaled quantum mechanical (SQM) method was performed for the vibrational analysis. Most stable conformational isomer of the compound is independent of the solvent effect. Results of SQM method are very successful in determining the solvent effect on vibrational frequency. Experimental and theoretical findings from the present search will be useful to understand structural characteristics of phenylboronic acid derivatives. 2,3-dimetoksifenil boronik asit molekülünün (2,3-dmpba; C6H3(OCH3)2B(OH)2) konformasyonel yapısı ve hidroksil (OH) gerilmeleri titreşimi üzerindeki çözücü etkisi Fourier dönüşümlü kızılötesi spektroskopisi (FTIR) ve yoğunluk fonksiyonel teorisi (YFT) ile birlikte hem deneysel hem de teorik olarak araştırılmıştır. Hesaplamalar polarize süreklilik modeli (PCM) kullanılarak on sekiz farklı organik çözücüde ve bileşiğin dört konformasyonel izomeri üzerinde odaklanmıştır. Titreşim analizleri için skalanmış kuantum mekanik model (SQM) kullanılmıştır. Ele alınan molekülün en kararlı konformasyonel izomeri çözücü etkisinden bağımsızdır. SQM metodu titreşim frekansları üzerindeki çözücü etkisini belirlemede oldukça başarılıdır. Bu çalışmadan elde edilen deneysel ve teorik tüm bulgular fenil boronik asit türevlerinin yapısal karakteristiklerini anlamada faydalı olacaktır.


Introduction
Boronic acid is a compound related to boric acid in which one of the three hydroxyl groups is replaced by an alkyl or aryl group. Boron and boronic acid-based include large number of potentials of related application in medicine, biology, material science and supramolecular or analytical chemistry [1]- [2]. A variety of typical properties of boronic acids enable them to be well suitable for practices in biomedicine [2]. Polymers including boronic acid have a wide range of uses in various biomedical applications such as management of HIV, obesity, diabetes, and cancer [3].

Experimental
2,3-dmpba was commercially obtained from Sigma Aldrich and chloroform, methanol, ethanol and dichloromethane solvents were procured from Merck. FTIR spectrum of free and solid 2,3-dmpba wereoptimi reported via Potassium Bromide (KBr) pellet technique by Perkin Elmer Frontier FT-IR spectrophotometer at a resolution of 2 cm -1 . Infrared spectra of 2,3-dmpba in solutions were recorded by a deuterated triglycine sulfate detector. Concentrations of 2,3-dmpba in the pure solvents ranged from 0.28 to 0.31 mol/l. Solvents of 25 µl were placed between CaF2 windows whose cell thickness was 12 µm.

Calculational details
Many possible conformational isomers could be proposed for 2,3-dmpba molecule. However, the discussion in this research is limited to cis-cis (CC), cis-trans (CT), trans-cis (TC) and transtrans (TT) forms ( Figure 1). Gaussian 09 was used for all calculations [30]. The optimized molecular structures were viewed with the GaussView program [31]. Calculations were performed by DFT method at B3LYP/6-31++G** in the gas phase and solutions. PCM model was employed to assess the solvent effect [32]. After, optimization processes were repeated with no geometric constraints until imaginary frequencies were not seen, calculations were performed for vibrational frequency under the same theory. Harmonic vibrational frequencies were scaled according to 0.955 [33] and SQM [34], [35]. Mole fractions for the isomers were calculated as given before [36], [37].

Results and discussion
Optimization energies of four isomers of the compound in eighteen different solvents are given in Table 1  Solvation is the process of interaction between solvent and solute molecules and is in part due to the attraction of a charge for a dipole. If the solute has polarity, solvent molecules will be thus drawn to the solute molecules. The greater the polarity of the solvent, the more the attraction is and therefore the more close attraction of the solvent molecules to the solute molecules is. Thus more electrostatic work is performed and so is more energy lost by the system, which inevitably turns more stable [38]. As seen from Table 1 and Figure 2, since dielectric constant of the solvent increases for the all forms, the molecule becomes more stable.
According to direction of various substituents in the gas phase, 3,4-dichloro [18], 2,4-dimethoxy [19], 2,3-difluoro [21] and 3,5-difluoro phenylboronic acid [23] prefer to CT form whereas the CC conformer is the most stable for 2,6-dimethoxy phenylboronic acid [20]. Optimized relative energies and mole fractions for all forms of 2,3-dmpba in different medium are listed in Table 2. Computed optimize energies indicate that the CT form is more stable than CC, TC and TT forms by 7.77-9.57 kcal/mol, 9.11-10.63 kcal/mol and 10.10-13.97 kcal/mol correspondingly. According to results of mole fraction computations of isomers, the title molecule prefers to CT conformational isomer with the probability of 100% for all medium ( Table 2). Table 3 presents the calculated lengths of hydroxyl bond and dipole moments of 2,3-dmpba, from which the OH bond lengths in CT form are seen to exhibit a linear correlations with the hydroxyl stretching frequencies of the compound as R 2 =0.99484 (C) and 0.99554 (T). Dipole moment of the compound increases gradually by solvent polarity. It is in agreement with the literature. However, it is inversely proportional with the hydroxyl stretching frequencies. As seen from Figure 3, there is good and linear correlation between OH stretching frequencies and dipole moments (R 2 =0.99466). Length of OH bond increases as the polarity of the solvent does. Hydroxyl stretching frequency should therefore decrease. It follows from Table 3 that this requirement is significantly fulfilled for the compound and OH frequencies decreases by increases in the bond lengths (R 2 =0.99956). Hydroxyl stretching frequencies are inversely proportional to the polarity of the solvent (Figure 2).
In Table 4, theoretical OH stretching vibrations scaled by literature coefficient and SQM are also given together with their experimental values. Correlation values between the experimental and computed vibrational frequencies are found to be 0.76684 for scaling factor and 0.99872 for SQM. The biggest difference between the experimental and theoretical frequencies is 133 cm -1 for scaling factor in literature and 29 cm -1 for SQM. Hence, there is a poor agreement between the theoretically scaled frequencies by scaling factor of the B3LYP/6-31++G** and those obtained experimentally. However, the predicted values by SQM show a good correlation with experimental data and this method constitutes a reliable complement the understanding of vibrational bands of the investigated compound.    OH 1 (C) and OH 2 (C) are scaled frequencies by 0.955 [33] and SQM [34,35].

Conclusions
Theoretical and experimental works have been performed by using DFT and FTIR to investigate solvent effect on the structure and hydroxyl stretching vibration of 2,3-dmpba as phenylboronic acid derivatives. There is no solvent effect on conformational isomers of the compound. Solvent induced OH frequencies are inversely proportional with the dipole moment, bond length and dielectric constant. Unscaled and scaled frequencies by B3LYP/6-31++G** have poor correlations with experimental data whereas SQM results are in excellent agreement and it is very successful in revealing the dielectricinduced solvent effect on the vibrational frequency.

Acknowledgements
This work was supported by Research Fund of the Ege University (Project Number: 2016-FEN-032).