INTRODUCTION

Pyridines are important heterocyclic organic compounds in chemistry and especially in biochemistry. They are given by the closed formula C5H5N and are found in the structure of many important compounds and ligands. Over the past decade, thousands of scientific articles have been published on pyridine, its derivatives and metal complexes due to their biological and chemical significance. 3-Fluoropyridine (C5H4FN, 3‑FP), 3-chloropyridine (C5H4ClN, 3-CP), and 3‑bromopyridine (C5H4BrN, 3-BP) are important pyridine derivatives which show bioactivity similar to pyridine. Due to their biological and pharmacological significance, many studies have been made on these molecules, their derivatives and metal complexes [1–3]. The first detailed examination of the vibrational frequencies of 3-FP, 3-CP, and 3-BP molecules was made by Green et all. and the results obtained were published in 1963 [4]. In some studies, it has been determined that derivatives of these molecules exhibit antidepressant and antibacterial properties [5, 6]. On the other hand, many studies have recently been published on the spectroscopic properties of these three structures. Boopalachandran and Laane [7] studied the spectroscopic and structural properties of 2-FP and 3-FP. In 2011, Akalin and Akyüz [8] studied the structure and vibrational properties of free 3-CP and its Zn(II) complexes using spectroscopic methods. Later, Boopalachandran [9] made some researches on vibrational frequencies and structures of 2-CP, 3-CP, 2-BP, and 3-BP.

Although many studies published on the structure and spectroscopic properties of 3-FP, 3-CP, and 3-BP molecules are found in the literature, there is no detailed study on the structural and vibrational properties of these molecules in solvent environments. Examination of solvent effects on molecular structures is very important for computational chemistry applications. Solvents play a very effective role in chemical reactions and can seriously change the structural and vibrational properties of any molecule [10]. In addition, the investigation of solvent effects is pharmacologically important because they can significantly affect the extent of transport, transport, and extent of absorption of living organisms [11].

In this study, solvent effects on the structural and vibrational properties of 3-FP, 3-CP, and 3-BP molecules have been investigated in detail in order to overcome the deficiencies found in the literature. These properties of the molecules have been theoretically investigated in different dielectric media such as benzene (C6H6, \(\mathcal{E}\) = 2.27), toluene (PhMe, \(\mathcal{E}\) = 2.37), chloroform (CHLF, \(\mathcal{E}\) = 4.71), dichloromethane (DCM, \(\mathcal{E}\) = 8.93), ethanol (EtOH, \(\mathcal{E}\) = 24.85), dimethylsulfoxide (DMSO \(\mathcal{E}\) = 46.83), and water (H2O, \(\mathcal{E}\) = 78.36) in addition to the investigations carried out in a vacuum (\(\mathcal{E}\) = 1.00) environment.

COMPUTATIONAL METHODS

The DFT/B3LYP method and the 6-311++G(d,p) basis set was used for calculate all examined physical and chemical properties of the 3-FP, 3-CP, and 3-BP molecules. All calculations were done on a PC using Gaussian03 [12] and Gaussview [13] programs. Optimizations of 3-FP, 3-CP, and 3-BP molecules was performed in different solvent environments such as vacuum, C6H6, PhMe, CHLF, DCM, EtOH, DMSO, and H2O. The vibrational frequencies were computed in the solvent environments from the optimized structures. In addition, the vibrational frequencies are scaled by 0.98 for 0–1800 cm–1 range, 0.96 for 1800–3600 cm–1 range [14]. The VEDA4 program [15] were used to characterize the fundamental vibrational modes. Also, entropy and heat capacity values at different temperatures are obtained in solvent environments by using vibrational frequencies.

The electronic properties of the molecules in vacuum and solvent media are calculated from considering total energies and Koopmans’ theorem, ionization potential I = –EHOMO and electron affinity A = ‒ELUMO can be described. Parr et al. [16] explained to chemical potential as μ = (EHOMO+ ELUMO)/2, chemical hardness as η = (ELUMO– EHOMO)/2 and finally electrophilicity as ω = μ2/2η.

RESULTS AND DISCUSSIONS

Geometry Optimizations, Energetics, and Thermochemical Properties

The optimized molecular structures of 3-FP, 3‑CP, and 3-BP determined by the 6-311++G(d,p) basis set are given in Fig. 1. In addition, some calculated important geometric parameters of these three structures in different solvent environments are tabulated in Table 1 together with experimental values from similar structures in the literature [17, 18].

Fig. 1.
figure 1

Optimized molecular structures of 3-FP, 3-CP, and 3-BP in vacuum.

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Table 1. Selected experimental and calculated bond lengths and bond angles of 3-FP, 3-CP, 3-BP in different media
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The 3-FP, 3-CP, and 3-BP molecules are closed ring structures and the bonds in the ring plane are not expected to be affected much from the changing solvent environment, generally. For these three structures, the bond lengths expected to be most influenced by the changing solvent medium are 2C-11X (X = F, Cl, Br) outside the ring. As a matter of fact, if Table 1 is examined, the bonds outside the 2C-11X show only 0.001–0.002 Å changes from the vacuum medium to the solvent media while the 2C-11X bonds shows between 0.004 and 0.007 Å. In addition, Table 1 also shows that all calculated geometric parameters are well matched to experimental X-ray diffraction data from the literature.

As expected, there are dramatic differences in C‒H bond lengths. As noted in many studies in the literature the reason of this is that because of the low scattering factors of hydrogen atoms in X-ray diffraction, experimental bond lengths of C‒H bonds are shorter than the calculated ones. The 1C‒2C‒11F, 3C‒2C‒11F, 1C‒2C‒11Cl, 3C‒2C‒11Cl, 1C‒2C–11Br, and 3C‒2C‒11Br angles outside the ring were much more severely affected by the changing solvent environment, while very small changes were observed for the angles in the pyridine ring. There is a good agreement between the experimental values from the literature and the values calculated. Since small changes in molecular parameters can cause very serious shifts in the vibration frequencies, these changes in the bond parameters will be very important in studying the vibrational modes.

The calculated total energies and zero-point vibrational energies of 3-FP, 3-CP, and 3-BP structures were given in Table 2 at 298.15 K. As can be seen from the table, all three structures exhibited the same characteristic behavior in changing solvent environments. Decreases were observed in the total and zero-point vibrational energies of the structures as the solvent polarity increased. As a natural and expected result of solvent effects, all structures have a more stable structure in the solvent environments than in the vacuum environment. A dipole in the molecule will induce a dipole in the medium. The electric field applied to the solute by the solvent dipole will in turn interact with the molecular dipole to lead to net stabilization [19]. While there is not much difference between the ZPVE energies for the 3-FP, 3-CP, and 3-BP in the molecular structure, it appears that there is a very serious difference in total energies.

Table 2.   The calculated total energies (T.E. in Hartree) and zero-point vibrational energies (ZPVE in kcal/mol) of the structures in 298.15 K
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The calculated entropies and heat capacities of the structures at different temperatures and in different solvent media were also given in Table 3 to see the effects of temperature and environment changing. The thermochemical properties of the structures were severely affected by the solvent environment and the increased temperature. In calculating the thermal properties of any molecule, contributions come to partition function, entropy, internal energy and constant volume heat capacity from each vibrational mode. Each of the 3N – 6 (or 3N – 5 for linear molecules) vibrational modes has a characteristic vibrational temperature. Because these contributions originate from vibrations, the solvent-induced changes in vibrations alter the thermochemical properties [20].

Table 3.   The calculated thermochemical properties of the structures in different temperatures and in different media (cal/(mol K))
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Vibrational Modes and Assignments

Vibrational spectroscopy is a very important instrument for molecular structure studies. Since the vibrations of the atoms forming the molecules cause a characteristic vibration band, very useful information about the molecular structure can be obtained using vibrational spectroscopy. As mentioned in the introduction of this paper, there are many studies in the literature about vibrational properties for 3-FP, 3-CP, and 3-BP molecules. Therefore, experimental IR spectra of these molecules were taken from the literature [21]. In this study, the vibrational frequencies and intensities of 3-FP, 3-CP, and 3-BP were calculated to be very well compatible with the experimental values. In addition, the effects of solvent environments on vibrational frequencies and intensities have been examined in detail. The 3-FP, 3-CP, and 3-BP structures have 11 atoms, and since they are not linear, there are 3N – 6 = 33 vibration modes (N is the number of atoms). The selected experimental and calculated vibrational modes of 3-FP are given in the Table 4.

Table 4.   Selected experimental and calculated vibrational modes of 3-FP
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Table 4 clearly shows that C–H vibrations are very seriously affected by the changing solvent environment. Also, when Table 4 is examined, it is seen that the vibrational frequencies and intensities calculated in the vacuum environment are very close to the experimental values. The deviations between the experimental and calculated frequencies ranges from 1–21 cm–1 for the 0–1800 cm–1 region. The solvent environment caused significant shifts in all vibration frequencies and in their intensities. The strongest band seen in the experimental spectrum is 1235 s and this mode is calculated as the strongest IR mode at 1221 cm–1. This mode has assigned as F–C and C–C stretching vibration. This band is the band most affected by the solvent environment, at the same time. The vibrational modes that are least affected by the changing solvent environment are the H–C–C–N, H–C–C, and F–C–C–T torsional modes. Solvent-induced changes at 3000–3100 cm–1, where C–H stretching modes are observed, are much greater than at other sites.

In the Table 5, selected experimental and calculated vibrational modes of 3-CP are given. For the 3‑CP structure, Table 5 shows that the vibrations in the C–H region are severely affected by the solvent medium. Also, the environment in which the calculated C–H stretching vibrations are most compatible with the experimental values is the vacuum. When Table 5 is examined, it is seen that the band calculated at 1096 cm–1 in vacuum and experimentally at 1107 cm–1 is the strongest vibrational mode. It is mainly caused by the Cl–C stretching vibration. This mode is also one of the vibrational modes most affected by the solvent medium. The strong bands observed at 702, 795, 1012, and 1411 cm–1 in the experimental spectrum correspond to calculated strong bands at 703, 792, 1011, and 1421 cm–1, respectively.

Table 5.   Selected experimental and calculated vibrational modes of 3-CP
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Table 6 shows the vibration modes of 3-BP. As in other structures, the strongest vibrational in 3-BP is mode 13, which contains the Br–C stretching vibration. Since the Br atom in the 3-BP structure is a heavier atom than Cl and F in the other structures, it is an expected result that the solvent effects on this structure are more limited. For other constructions, up to 26 cm–1 shifts were observed from the vacuum to the water medium in frequencies, while 4 cm–1 shifts occurred for the 3-BP structure.

Table 6.   Selected experimental and calculated vibrational modes of 3-BP
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The common result obtained in the study of vibrational modes, as in the comparison of experimental and calculated geometric parameters, is that the changing solvent environment has less influence on the movements of the atoms and bonds in the plane of the ring. Changing solvent environment have much more serious effects on the vibrations of C–H and C‒X (X = F, Cl, Br) atoms. Tables 4–6 confirm these results. Changes in vibration modes are important when moving from gas to solution.

HOMO–LUMO Energies and Chemical Reactivity

In this study, we have also computed the highest occupied molecular orbital (HOMO) energies, lowest unoccupied molecular orbital (LUMO) energies and their energy gaps for 3-FP, 3-CP, and 3-BP. HOMO and LUMO energies are important parameters in computational chemistry because they help define many physical and chemical properties. The energy gap between HOMO–LUMO is a considerable parameter in determining molecular electrical transport properties. the energy of the HOMO is directly related to the ionization potential, and LUMO energy is directly related to the electron affinity. This is also used by the frontier electron density for estimating the most reactive position in p-electron systems and also explains several types of reaction in conjugated system [22].

In Table 7 calculated dipole moments and chemical reactivities of the structures in different dielectric media are seen. It is seen that increasing the dielectric constant causes regular change in HOMO and LUMO energies. Similarly, the dipole moments of the structures increases regularly with increasing dielectric constant. Larger dipole moments cause greater stabilization in solution phase. At the same time, changing solvent polarity directly affects chemical reactivity in Table 7. The HOMO–LUMO contour maps of 3-FP, 3-CP, and 3-BP were given in Fig. 2. The positive parts are represented in red and negative parts are represented in green color. Moreover, for the 3-FP, HOMO shows bonding character between 1C–2C–3C and 4C–5C–6N atoms. LUMO shows bonding character between 2C–1C–8H, 5C–4C–9H, and 7H–3C atoms. For the 3-CP and 3-BP, the same bonding and antibonding characters are available. In Fig. 2, it is noticeable that 11Cl and 11Br atoms are positive while 11F1 is negative. The energy gap between HOMO–LUMO decreases from 3-FP to 3‑BP.

Table 7.   Calculated chemical reactivity (eV) and dipole moments of the structures in different media
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Fig. 2.
figure 2

HOMO–LUMO contour maps and energy gaps of 3-FP, 3-CP, and 3-BP in vacuum.

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Molecular Electrostatic Potential

Molecular electrostatic potential (MEP) maps are drawings that visualize the distribution of charge on the molecule in three dimensions. These maps give the shape, size and charge distribution of a molecule. Generally, the red regions in the map give low electrostatic potential energy and low electronegativity, while the blue regions symbolize high electrostatic potential energy and high electronegativity. MEP maps also provide important information about the nature of molecular bonds. They say a lot about the difference in electronegativity.

To predict reactive sites of electrophilic and nucleophilic attack for 3FP, 3-CP, and 3-BP, MEPs were calculated and in Fig. 3, molecular electrostatic potential surface contour maps of 3FP, 3-CP, and 3‑BP in vacuum and water media are drawn. As can see from the Fig. 3, full red or full blue colors are dominant on the MEP map. Particularly, nitrogen atoms of the molecules have mostly red regions and hydrogen atoms have blue colors, which indicates that the difference in electronegativity is high. As expected, positive charge densities are localized on hydrogen atoms. Cl and Br atoms have gray colors while the F atom has yellow region. In this case, we can say that negative charge density is localized on F atom.

Fig. 3.
figure 3

Molecular electrostatic potential surface contour maps of 3FP, 3-CP, and 3-BP in vacuum and water media.

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CONCLUSIONS

In this study, for the 3-fluoro-, 3-chloro-, 3-bromopyridine, some physical and chemical properties have been examined in vacuum, C6H6, PhMe, CHLF, DCM, EtOH, DMSO, and H2O media. Total energies, optimized molecular structures, entropies and heat capacities at different temperatures, HOMO–LUMO energies and chemical reactivities were calculated. The vibrational frequencies of the structures in vacuum and solvent environments were calculated and compared with the experimental data from the literature. In addition, molecular electrostatic potential maps for 3-FP, 3-CP, and 3-BP were drawn and atomic charges were determined. The following conclusions were reached at the end of the study.

• It has been determined that the changing solvent environments has limited effects on the molecular parameters of these three structures. Particularly, the bond lengths and bond angles remaining in the ring planes are little affected by the changing solvent media. However, the calculated molecular parameters are quite compatible with the experimental data available in the literature.

• The increased polarity of the environment and the increased temperature increase the entropy and heat capacities of the structures.

• The calculated vibrational frequencies and intensities for the three structures are very compatible with the experimental data from the literature. Although the changing solvent environments has little effect on the molecular structures, they have serious effects on vibration frequencies and their intensities. Especially, C–H vibrations are greatly influenced by environments changes.

• The changing solvent environments also change the electron affinities, ionization potentials, global hardness, chemical potentials, electrophilicity and dipole moments for 3-FP, 3-CP, and 3-BP.