Introduction

Pyrazines, also known as p-diazines (or 1,4-diazines, Scheme 1), are compounds containing a symmetrical (D 2h) aromatic heterocycle C4H4N2. In nature, there are many substituted pyrazines that carry substituents at one or more of the four ring carbon atoms. The substituents include oxygenated functional groups like alkoxy groups and acyl groups or sulfur-containing thiol or sulfide groups. Only among alkylpyrazines (containing only carbon and hydrogen substituents) ca. 70 different compounds of that type have been identified in nature [1, 2]. The diversity of structures and roles pyrazine derivatives play in living organisms began to arouse the interest of researchers. The pyrazine derivatives have numerous prominent pharmacological effects: aspergillic acid, hydroxyaspergillic acid and other antibiotics of similar structure possess antibacterial activities [1–5]. Emimycin (3-hydroxypyrazine N-oxide), first isolated from Streptomyces, has been found a potent and selective inhibitor of the growth and nucleic acid synthesis in Toxoplasma gondii in human fibroblasts. Sulfonamides with pyrazine moiety are known to have high antibacterial activity [6]. Derivatives such as phenazine are well known for their antitumor, antibiotic and diuretic activities. Synthetic pyrazine derivatives exhibit a wide variety of pharmacological properties, including hypoglycemic [7–10] and diuretic [11–13] action. Pyrazinamide and its morpholino-methylene derivative act as tuberculostatic agents [14, 15]. Structural modifications of the pyrazine ring substituents in these compounds cause modulation in their biological activity [12, 16–20]. Nicotinic and isonicotinic amidrazones are also reported in the literature as antibacterial agents [16, 21]. They also act as diuretic [22] and antimycotic [23]. Tetramethylpyrazine (also known as ligustrazine) is reported to scavenge superoxide anion and decrease nitric oxide production in human leukocytes [24].. For its active cardiovascular properties such as anti-platelet activity and free radical scavenging [25–27], ligustrazine has been used for the treatment of cardiovascular diseases (CVDs) in the clinic [28–30].

Scheme 1
scheme 1

General structure of diazines

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Pyrazines, synthesised chemically or biologically, are also used as flavoring additives. The pyrazine motif is observed in a large number of compounds that are responsible for the unique flavor and aroma of several foodstuffs and wines [31, 32]. Orally administered substituted pyrazines are rapidly absorbed from the gastrointestinal tract and excreted [33]. It is reported in the literature that absorption of pyrazine derivatives is optimal at intestinal pH (ca. 6–7) [3, 5]. The high incidence of pyrazine derivatives from the flavors of food systems and their effectiveness at very low concentrations has aroused a great interest in perfume industry [34]. Pyrazine ring is present in condensed azine dyes, for example, eurhodines, indulenes and safranines [35]. Nowadays, the pyrazine ring is a part of many polycyclic compounds of biological and/or industrial significance; examples are quinoxalines, phenazines and bio-luminescent natural products pteridines, flavins and their derivatives.

Compounds containing the quinoxaline fragment, such as Diquat, Propaquizafop and Quizalofop-ethyl, are very useful herbicides and have been used to control aquatic macrophytes [36]. While Diquat’s activity consists mostly in its interaction with the photosystem I and via subsequent formation of free radicals, the two latter were shown to inhibit acetylCoA carboxylase [37, 38]. Nakamura et al. [39] synthesized sixty-six 2,3-dicyano-5-substituted pyrazines and measured their herbicidal activities against barnyard grass in pot tests to clarify the relationship between chemical structure and activity. The activity of 59 derivatives showed parabolic dependence on the hydrophobic substituent parameter at the 5-position of the pyrazine ring, indicating that the compounds should pass through a number of lipoidal–aqueous interfaces to reach a critical site for biological activity. It was found that the moiety of 2,3-dicyanopyrazine is essential for herbic ideal activity, and the 5-substituent on the pyrazine ring plays an important role in determining the potency of this activity and that para-substituted phenyl derivatives show undesirable effects on the potency of the activity at the ultimate site of herbicidal action. The results indicated that the structure of the substituted dicyanopyrazine moieties is an important function for the herbicidal activity and that the activity of these compounds is determined by the hydrophobic and steric parameters of substituents at the pyrazine ring. Similarly, Doležal et al. [40] prepared a series of substituted N-phenylpyrazine-2-carboxamides and diazachalcones. The most effective herbicide from the series was 6-chloro-N-(5-chloro-2-hydroxyphenyl)-pyrazine-2-carboxamide (IC50 = 8 μmol). The inhibitory activity of ortho-hydroxyl substituted derivatives was greater than that of their para-hydroxyl substituted isomers. An important lesson from the above mentioned studies comes from the fact that even subtle modifications of the studied pyrazine analogues have a high impact on the biological activity of a given compound. It is the time to conduct further studies aimed at rationalizing the biological activities found in order to develop more effective and clinically interesting compounds.

A renewed interest in the chemistry of pyrazine derivatives can be largely attributed to the major advances of chemotherapy, where heterocycles have been particularly prominent. Among the pyrazine-derived anticancer drugs, an epitome is a dipeptide Bortezomib, [(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl] boronic acid, a 20S proteasome complex inhibitor that acts by disrupting various cell signaling pathways, thereby leading to cell cycle arrest, apoptosis and inhibition of angiogenesis. The hallmark of bortezomib action is the inhibition of NF-κB, thereby interfering with NF-κB-mediated cell survival, tumor growth and angiogenesis [41] and has been applied in the treatment of cancer [42]. In the study of Kamal et al. [43], a series of oxindole derivatives of imidazo[1,5-a]pyrazines were prepared and evaluated for their anticancer activity against a panel of 52 human tumor cell lines derived from nine different cancer types: leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast. Among them one compound, namely 3-(E)-1-[3-(2-Fluorophenyl)imidazo[1,5-a]pyridin-1-yl]methylidene-2-indolinone, showed significant anticancer activity with GI50 values ranging from 1.54 to 13.0 μM. A series of fifty-one pyrazinyl derivatives have been synthesized by Rodrigues et al. [44] and evaluated for their activity against four cancer cell lines, exhibiting good cytotoxicity (IC50 ranging from 1.1 to 5.6 μg mL−1). Structure–activity relationship (SAR) analysis indicated that the hydroxyl group located in ortho position is critical for the biological activity of these compounds. The presence of hydroxyl groups on benzene ring plays an important role in the anticancer activity of this series, feature especially observed in disubstituted derivatives. The mentioned instances on new pyrazine-derived drug development give a clear notion, how important for the successful research is understanding of the SAR analysis approach.

In the frame of our previous works, we studied the effect of over 40 metal cations on the electronic system, physicochemical and biological properties of different ligands—derivatives of benzoic [45–49] acids. The complexations of aromatic carboxylic acids by metal cations change the electronic charge distribution within the aromatic ring and the carboxylate anion. So far, our studies showed that the effect of metal cation on the electronic structure of pyridine ring of pyridinecarboxylic acids depends on the position of nitrogen atom within the carboxylic acid structure. In this work, the effect of alkali metal cations on the electronic structure of derivatives of pyrazine was studied. We have studied the salts of pyrazine 2-carboxylic acid (2PCA) and pyrazine 2,3-dicarboxylic acid (2,3PDCA) alkali metal salts. A range of complementary methods were used to determine the effect of alkali metals on the changes in the distribution of electronic charge in the pyrazine ring of the analyzed acids. As part of the work, we also investigated the impact of alkali metals on the (thermal stabilization) of the 2-pyrazinecarboxylic and 2,3-pyrazinedicarboxylic acids. These studies also allowed, along with the elementary analysis, to determine the degree of hydration of the tested salts.

Experimental and theoretical calculations

Sample preparation

The alkali metal salt of 2-pyrazinecarboxylic (2PCA) and 2,3-pyrazinedicarboxylic acids (2,3PDCA) was prepared by dissolving appropriate weighed amount of particular acids in hot aqueous solution of alkali metal hydroxides in a stoichiometric ratio ligand/metal—1:1 for 2-pyrazinecarboxylates and 1:2 for 2,3-pyrazinedicarboxylates. To 1 mmol of 2-PCA 10 cm3 of 0.1 mol/L alkali metal hydroxide solution in water was added. The solutions were than heated in a shaker to ca 80°C for 1 h. Then, the solutions were left at RT for 24 h. Next, they were evaporated and dried at 50°C for 24 h. In order to obtain alkali metal salts with 2,3-pyrazinedicarboxylic acid, 0.1 mmol of acid was diluted in 20 mL of corresponding metal hydroxide (0.1 mol L−1). Salts of 2,3-pyrazinedicarboxylate acid were prepared analogically.

Measurement and calculation

The FT-IR spectra were recorded with an Alfa (Bruker) spectrometer within the range of 400–4000 cm−1. Samples in the solid state were measured in KBr matrix pellets and ATR technique. FT-Raman spectra of solid samples were recorded in the range of 400–4000 cm−1 with a MultiRam (Bruker) spectrometer. The resolution of the spectrometer was 1 cm−1. The 1H and 13C NMR spectra of D2O solution of studied compounds were recorded with a Bruker Avance II 400 MHz unit at room temperature. TMS was used as an internal reference. To calculate optimized geometrical structures of 2-pyrazinecarboxylic and 2,3-pyrazinecarboxylic acid and lithium, sodium and potassium salts, quantum–mechanical method was used: density functional (DFT) hybrid method B3LYP with non-local correlation provided by Lee–Young–Parr expression. All calculations were carried out with functional base 6-311++G(d,p). Calculations were performed using the Gaussian09 package [50]. Experimental spectra were interpreted in terms of calculated at DFT method in B3LYP/6-311++G(d,p) level and literature data [51]. Theoretical wavenumbers were scaled according to the formula: ν scaled = 0.98·ν calculated for B3LYP/6-311++G(d,p) level method [52] Chemical shifts (δ i) were calculated by subtracting the appropriate isotopic part of the shielding tensor (σ i) from that of TMS (σ TMS): δ i = σ TMS − σ i (ppm). The isotropic shielding constants for TMS calculated using the DFT method at the same level of theory were equal to 31.8201 ppm and 182.4485 ppm for the 1H nuclei and the 13C nuclei, respectively. The electronic charge distribution was calculated with natural bond orbital (NBO) [53] at B3LYP/6-311++G(d,p) level of theory. The HOMA [54] and Bird I 6 [55] aromaticity indices were calculated for theoretical structures. The products of dehydration and decomposition processes were determined from the TG curves. Thermogravimetric analysis (TG) was performed on a Mettler Toledo Star TGA/DSC1 unit. Argon was used as a purge gas (20 mL min−1). Samples between 2 and 4 mg were placed in aluminum pans and heated from 50 to 850 °C with a heating rate of 10 °C min−1.

Results and discussion

Thermal study and elemental analysis

Alkali metal salts of the pyrazino 2-carboxylic acid 2,3-pyrazine dicarboxylic acids were dried for 24 h at 50 °C. The degree of hydration of the salt defined on the basis of thermogravimetric and elemental analysis was limited. Sodium, potassium and rubidium 2-pyrazinecarboxylates and sodium 2,3-pyrazinecarboxylate were anhydrous. For other salts, the degree of hydration ranged from 0.5 to 1.5 H2O per molecule (Tables 1, 2; Fig. 1). Dehydration of the salts studied takes place in a single step (for all the hydrated salts). The press of thermal decomposition of both ligands is a single step press occurring at similar temperatures. 2,3-Pyrazinecarboxylic acid decomposes at about 210 °C, and 2-pyrazinecarboxylic acid at about 230 °C. Thermal decomposition of the salts studied takes place in several stages. The products of the first stage of the lithium salts decomposition are lithium carbonates and organic carbon residues formed during the decomposition of the aromatic ring (Tables 1, 2; Figs. 1, 2). For both ligands, press takes place at the same temperature of 350–450 °C. Further heating of lithium salts leads to combustion of organic carbon residue. The final product of this decomposition step is lithium carbonate (at a temperature of about 850 °C for 2-pyrazinecarboxylate (Fig. 1) and 750 °C for 2,3-pyrazinedicarboxylate (Fig. 2). The sodium 2-pyrazinecarboxylic probably undergoes thermal decomposition into sodium carbonate at a temperature higher than 850 °C (outside the test temperature range). Intermediate product of this decomposition is a mixture of sodium carbonate and residual organic carbon from the decomposition of the pyrazine ring (this product is formed in the temperature range of 500–600 °C). Thermal decomposition of sodium 2,3-pyrazinedicarboxylate yields a mixture of sodium carbonate and organic carbon, which decompose to sodium carbonate at a temperature above 850 °C. The final decomposition product of potassium 2,3-pyrazinedicarboxylate is potassium carbonate (formed at a temperature above 800 °C). The intermediate product is a mixture of potassium carbonate and residual organic carbon from the decomposition of the pyrazine ring (this product is formed in the temperature range of 350–490 °C).

Table 1 Elemental analysis and thermogravimetric analysis for lithium, sodium, potassium, rubidium and cesium 2-pyrazinecarboxylates
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Table 2 Elemental analysis and thermogravimetric analysis for lithium, sodium, potassium, rubidium and cesium 2,3-pyrazinedicarboxylates
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Fig. 1
figure 1

Curves of thermal decomposition (TG and DTG curves) of alkali metal salts with 2-pyrazinecarboxylic acid (2PCA)—left diagrams and 2,3-pyrazinedicarboxylic acid (2,3PDCA)—right diagrams

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Fig. 2
figure 2

Curves of thermal decomposition (TG and DTG curves) of alkali metal salts with 2,3-pyrazinedicarboxylic acid (2,3PDCA)

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In the case of potassium 2-pyrazinecarboxylate, the final product of degradation is potassium carbonate (at a temperature of 850 °C). An intermediate product is a mixture of potassium carbonate and organic carbon. The process of thermal decomposition of 2-pyrazinecarboxylate rubidium occurs in two stages. In the first stage taking place at a temperature of from 340 to 390 °C, a mixture of rubidium carbonate and organic carbon is formed (Fig. 1), and the second step yields rubidium carbonate (at a temperature of from 390 to 850 °C). The intermediate product of decomposition of rubidium 2,3-pyrazinedicarboxylate is a mixture of rubidium carbonate and residual organic carbon from the decomposition of the pyrazine ring (this product is formed in the temperature range of 350–400 °C). Further heating leads to unidentified products (Fig. 2).

The decomposition process of the cesium 2-pyrazinecarboxylate gives a mixture of cesium carbonate and carbon, which decomposes in the next step of heating, yielding probably the cesium oxide, Cs2O.

Also, heating of cesium salt of 2,3-pyrazine dicarboxylic acid also gave a mixture of cesium carbonate and organic carbon; nevertheless, further heating leads to the formation of other products that could not be identified (unknown stable breakdown products—probably the cesium oxide, Cs2O).

Comparing the curves of the thermal decomposition of the alkali metal salt of either acid, we observed that salts of 2-pyrazinecarboxylic acid decomposed at a slightly higher temperature than the salts of 2,3-pyrazinedicarboxylic acid. For all of the alkali metal salts of both ligands, thermal decomposition occurred yielding an intermediate product that was a mixture of alkali metal carbonate and organic carbon residues formed during decomposition of an aromatic acid. It was also observed that in the case of cesium salt, the carbonates formed were unstable and underwent further degradation at temperatures above 430 °C (2PCA acid salt) and above 700 °C (salt of 2,3PDCA).

IR and Raman study

Table 3 shows the wavenumbers and intensities of the bands present in IR spectra registered in the KBr matrix by ATR technique and as well those theoretically calculated by DFT (B3LYP-6-311++G**) and Raman spectra of 2-pyrazinecarboxylate and its salts with alkali metals. Table 4, in turn, shows the registered and calculated wavenumbers and intensities of the IR bands as well as the Raman spectra of 2,3-pyrazinedicarboxylate and alkali metal salts thereof. The experimental spectra were interpreted based on theoretical calculations and data presented in the literature [51]. The normal ring vibrations of aromatic acids and salts were assigned according to the Varsányi numbering [56]. Figure 3 shows the experimental spectrum recorded in KBr matrix and the Raman spectrum of 2-pyrazinecarboxylic acid and the chosen salt (of sodium). In the spectra of the salts, the characteristic vibrational bands of the carboxylate anion can be observed. These include asymmetric stretching vibration band of the carboxylate anion νasCOO− and symmetric stretching vibration band νsCOO−. For the salts of 2-pyrazinecarboxylate upon the coordination of the carboxyl group the alkali metal cation, there appears a single band of νasCOO− vibration, present in the studied salts in the wavenumber range: 1619–1615 cm−1 (IRKBr), 1631–1613 cm−1 (IRATR) and 1646–1617 cm−1 (Raman) and a single band of νsCOO− vibration present in the range of 1389–1381 cm−1 (IRKBr), 1385–1369 cm−1 (IRATR) and 1393–1382 cm−1 (Raman). There was also observed some single asymmetric and symmetric bending vibrations in the plane of the carboxylate anion βasCOO− and βsCOO− respectively at wavenumbers: 538–516 cm−1 (IRKBr), 548–517 cm−1 (IRATR) and 547–512 cm−1 (Raman) and 855–848 cm−1 (IRKBr), 854–840 cm−1 (IRATR) and 859–842 cm−1. In the spectra of alkali metal 2-pyrazinecarboxylates, there were also observed the symmetrical out-of-plane bending vibrations of the carboxylate anion γsCOO− in the ranges of: 807–795 cm−1 (IRKBr), 797–786 cm−1 (IRATR) and 799–786 cm−1 (Raman). The coordination of the alkali metal atom by the carboxyl group induces the formation of the carboxylate anion and the change in electron charge distribution within that group. Along with the change in an alkali metal atom in the salt (in the series Li–Na–K–Rb–Cs) the charge distribution and the degree of metal–ligand binding as manifested by changes in wavenumbers bands derived from the carboxylate anion vibration νsCOO− and νasCOO−. Change in the ionic character of bond is associated with the increase or decrease in the disparity of νsCOO− and νasCOO− band wavenumbers in the spectra of salt in the test series (parameter Δν = νasCOO − νsCOO−).

Table 3 Wavenumbers (cm−1), intensities and assignments of bands occurring in the IR (KBr, ATR and DFT) and Raman spectra of 2-pyrazinecarboxylic acid and lithium, sodium, potassium, rubidium and cesium 2-pyrazinecarboxylates
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Table 4 Wavenumbers (cm−1), intensities and assignments of bands occurring in the IR (KBr, ATR and DFT) and Raman spectra of 2,3-pyrazinedicarboxylic acid and lithium, sodium, potassium, rubidium and cesium 2,3-pyrazinedicarboxylates
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Fig. 3
figure 3

IRKBr (a, b) and Raman (c, d) spectra for 2-pyrazinecarboxylic acid (a, d) and sodium 2-pyrazinecarboxylate (b, c)

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We observed a decrease in the Δν the IR spectra are IRATR, IRKBr, Raman spectra in the studied salts in the series Li–Na–K–Rb–Cs. In the case of the IRKBr spectra, these changes were irregular in the studied series of metal salts. A similar effect was observed earlier in the case of alkali metal salts of other ligands, including 2-pyridinecarboxylic acid [57, 58]. We also observed the dependencies between some parameters of metals (including metal ion potential) and the values of the wavenumbers of carboxylate anion vibrations in the salts of the given metals with different ligands.

In the studied 2,3-pyrazinedicarboxylate alkali metal salts, the ratio of ligand to metal is 1:2. Both carboxyl groups of the ligand are substituted with an alkali metal. The spectra of these salts comprise each the two bands derived from symmetric stretching vibration νsCOO− carboxylate anion and two bands derived from asymmetric stretching vibration carboxylate anion νasCOO− (Fig. 4; Table 4). νasCOO− vibration bands appear at wavenumbers: 1641–1613 and 1600–1588 cm−1 (IRKBr), 1641–1612 and 1595–1585 cm−1 (IRATR) and 1631–1604 and 1604–1586 cm−1 (Raman). νsCOO− vibration bands appear at wavenumbers: 1398–1388 and 1361–1351 cm−1 (IRKBr), 1399–1389 and 1361–1351 cm−1 (IRATR) and 1401–1388 and 1366–1357 cm−1 (Raman). In the spectra of 2,3-pyrazinodicarboksylates of alkali metals, one can also observe two strands coming from asymmetric and symmetric in the plane bending vibrations of the carboxylate anion βasCOO− and βsCOO− and two symmetrical out-of-plane bending vibration bands of the carboxylate anion γsCOO− (Table 4). The wavenumbers of bands coming from the carboxylate anion vibrations change irregularly in the studied series of metal salts. The observed changes in the parameter Δν = νasCOO − νsCOO− for a series of 2,3-pyrazinedicarboxylates (Li–Na–K–Rb–Cs) are also irregular.

Fig. 4
figure 4

IRKBr (a, b) and Raman (c, d) spectra for 2,3-pyrazinedicarboxylic acid (a, d) and sodium 2,3-pyrazinedicarboxylate (b, c)

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Analyzing the values of wavenumbers and intensities of the bands derived from the vibration of the aromatic ring in the salts of 2PCA and 2,3PDCA acids, one can find a number of characteristic differences as compared to the spectra of ligands. Some of the bands present in the spectra of acids disappear for salts. Wavenumbers and intensities of most of the bands decrease in the salts in relation to the ligand. The disappearance of the bands, decrease in the intensity of the bands derived from the aromatic system and its shift toward lower wavenumbers in the IR and Raman spectra of the salts, compared to the spectrum of acid result from the decreased force constants and polarization of C–H and C–C chemical bonds in the ring. This is related to the perturbation of the electron charge distribution in the aromatic ring of the ligand upon the interaction of the alkali metal with the carboxyl group. From our previous works [57, 59, 60], it follows that the alkali metals disturb the electron system of the aromatic ring in a number of ligands, e.g., benzoic, salicylic and pyridinecarboxylic acids, as well as acids containing five-membered heterocyclic rings.

In the IRKBr, IRATR and Raman spectra of 2-pyrazinecarboxylates, as compared with the acid, one observes a disappearance of the band 7b associated with the vibration of the CH groups of the aromatic ring. The wavenumbers of several bands in the spectra of the salt decrease. These are the bands numbered: 20b, 8a, 8b, 19a, 19b, 18b, 6b, 16b (in the IRKBr spectra), 20b, 8b, 19b, 5, 11, 6a, 6b (in the IRATR spectra) and 20a, 8a 8b, 19b, 11, 6b, 16b (in the Raman spectra). It was also observed that the wavenumbers of some bands derived from the vibration of the aromatic ring increase in the salts, compared to the spectrum of the ligand. These bands are: 20a, 9a, 14, 13, 18a (in the IRKBr spectra), 20a, 13, 18a (in the IRATR spectra) and 14, 18a (in the Raman spectra). The IRKBr, IRATR and Raman spectra of the salts there occurred a deformation vibration band of the aromatic ring (labeled 4), which was absent in the spectrum of the acid. In the Raman spectra of the salts appeared bands marked with numbers 19a and 6a, which were not observed in the spectrum of the acid.

In the studied series of the alkali metal salts of 2-pyrazinecarboxylate, wavenumbers of many aromatic ring bands decrease regularly in the order Li–Na–K–Rb–Cs. These include the bands 8a, 8b, 19a, 19b, 9a, 18a (in the IRKBr and IRATR spectra) and 8a, 19b, 18a (in the Raman spectra). Based on the analysis of changes in the wavenumber ranges of an aromatic ring of 2-pyrazinecarboxylate, and salts thereof it can be concluded that alkali metals disturb the electronic system of the acid, and that the degree of perturbation increases in the studied series in the order Li–Na–K–Rb–Cs.

As compared to the free acid, in the spectra of the salt of 2,3-pyrazinedicarboxylate multiple bands derived from the vibration of the aromatic ring disappeared. These bands are indicated by numbers: 20a, 8a, 8b, 19a, 6a, 18b, 5, 4 (in the IRKBr spectra), 20a, 8a, 5, 4 (in the IRATR spectra) and 20a, 8a, 4, 6 (in the Raman spectra). Observed was a decrease in the wavenumbers of an aromatic ring vibration. These bands are indicated by numbers: 9a, 18a, 1 (in the IRKBr spectra), 8b, 19a, 9a, 18a, 14, 1 (in the IRATR spectra) and 20b, 8b, 19a, 18a, one (in the Raman spectra). Wavenumber of some vibrations of the aromatic ring increased in salts with respect to the ligand (lane 13 and 11 present in the IRKBr, IRATR and Raman spectra).

Changes in the aromatic ring vibration wavenumbers in the studied series of 2,3PDCA acid salts occur irregularly in the direction Li–Cs. In general, in instances of salts with monocarboxylic acids, these changes are regular in the series Li–Na–K–Rb–Cs (for example: 2-pyrazinecarboxylate [this work], 2-pyridinecarboxylates [48], 3-pyridinecarboxylates and 4-pyridinecarboxylates [47]. Based on changes in wavenumber and intensity of the aromatic ring vibration bands in the salts as compared to the ligand, it can be concluded that alkali metals disturb the electron charge distribution in the aromatic ring of 2,3-pyrazinedicarboxylic acid. The effect of alkali metals on the electron charge distribution (decrease in the charge distribution) in the pyrazine ring is much greater in the case of a dicarboxylic acid salt (2PCA) than for the monecarboxylate acid (2,3PDCA).

NMR study

Chemical shifts of the proton signals in 1H NMR spectra of alkali metal 2-pyrazinecarboxylates (H2: 8.90–9.01, H3: 8.45–8.62, H4: 8.29–8.54) display lower values than those for acids (values: H2: 9.19, H3: 8.84, H4: 8.79) (Table 5). Pyrazine aromatic ring system is disturbed due to the changes in the electron density around the protons of the aromatic ring upon substituting the alkali metal atom to the carboxyl group of the acid. Chemical shift values decrease toward Li–Na–K–Rb. In the case of cesium salt, the mentioned values are similar to those of the sodium salt. A 1H NMR spectrum was registered for 2,3-pyrazinedicarboxylate and its lithium salt. The spectra of the other salts of 2,3-pyrazinedicarboxylate were not registered, due to the very poor solubility of these salts in the available solvents. A comparison of the spectra of 2,3-pyrazinedicarboxylate and its lithium salt implies that lithium disturbs the aromatic ring charge distribution (Table 6). Proton chemical shift values (in experimental 1HNMR spectra for lithium 2,3-pyrazinedicarboxylate: H3, H4: 8.85) are lower in salt than in acid (H3, H4: 8.27). Theoretical calculations show that in the case of sodium and potassium salts chemical shift values are also lower than the corresponding chemical shifts for protons in the ligand. It is therefore concluded that the alkali metals disturb the electron system of the aromatic ring of 2,3-pyrazinedicarboxylate. Effect of alkali metals on the electronic charge distribution is higher in the case of 2,3-pyrazinecarboxylate. Changes in the chemical shifts of protons in the salts of a ligand are greater for 2,3-pyrazinedicarboxylates than 2-pyrazinecarboxylates. This is evidenced both by chemical shift values that were determined experimentally and those theoretically calculated.

Table 5 Values of the chemical shifts [ppm] in the spectra of 1H and 13C NMR of 2-pyrazinecarboxylic acid (2-PCA) and its salts determined experimentally and by a theoretical GIAO/B3LYP/6-311++G** method
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Table 6 Values of the chemical shifts [ppm] in the spectra of 1H and 13C NMR of 2-pyrazinedicarboxylic acid (2,3PDCA) and its salts determined experimentally and by a theoretical GIAO/B3LYP/6-311++G** method
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After substituting the alkali metal atom in the carboxyl group of 2-pyrazinecarboxylate a slight increase can be seen in chemical shifts of carbon of the carboxyl group in the 13C NMR spectra due to the decrease in the electron density around the carbon atom of the carboxyl group. Much more pronounced changes were observed in the chemical shifts of atoms of an aromatic ring. In the 2-pyrazinecarboxylates, the electron density on the carbon atoms numbered C1, C2, and C3 (Fig. 5a) increases in relation to that of the ligand, what is observed as a decrease in the chemical shifts in the spectra of 13C-NMR. The electron density at the C4 atom decreases—an increase is observed in 13C chemical shift values in the salts in relation to the acid. Changes in chemical shifts of carbons for 2-pyrazinecarboxylates of alkali metals with respect to 2-pyrazinecarboxylic acid indicate that alkali metals disturb the electron charge distribution in the aromatic ring of the ligand. An increase in the perturbation of the electron charge distribution was observed along the series Li–Na–K–Rb. A comparison of the chemical shifts in the spectra of 13C-NMR implies that the effect of cesium on the electron charge distribution of 2-pyrazinecarboxylic acid is similar to that of sodium (similar chemical shifts in the salts of sodium and cesium), which was confirmed by the proton spectra of the studied compounds.

Fig. 5
figure 5

Numbering of the atoms in the 2-pyrazinecarboxylic acid (a) and 2,3-pyrazinedicarboxylic acid (b)

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Significant changes in the chemical shifts of carbons in the 13C NMR spectrum were observed in the case of lithium substitution to the carboxyl groups of 2,3-pyrazinedicarboxylate. The values of the chemical shifts of atoms indicated C1 and C2 (Fig. 5b) decrease (indicating an increase in the electron density) and the remaining atoms of the aromatic ring increase (decrease in electron density). Changes in chemical shifts of carbons in the NMR spectra of the salt with respect to the ligand calculated theoretically are greater for alkali metal 2,3-pyrazinedicarboxylates than for 2-pyrazinecarboxylates.

Aromaticity and NBO analysis

Upon the substitution of the alkali metal atom to the carboxylic group of 2-pyrazinecarboxylic, and 2,3-pyrazinedicarboxylic acids, the aromaticity of the pyrazine ring decreased. Calculated HOMA aromaticity indices and Bird’s I 6 indices display the lower values for the salt in comparison with the ligands (Table 7). Comparing the ligand of Table 7, we found that alkali metals have much greater impact on the aromaticity change (decrease in the aromaticity index values) of 2,3-pyrazinedicarboxylic acid than of the 2-pyrazinecarboxylic acid.

Table 7 Aromaticity indices (HOMA, GEO, EN) and Bird’s index (I 6) for 2PCA, 2,3PDCA and their salts (lithium, sodium, potassium) (calculated for the structure optimized in B3LYP/6-311++G**)
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The values of the electronic charges in ligands (2PCA and 2,3PDCA) and their salts of lithium, sodium and potassium were calculated using NBO (natural bond orbital method). Upon the substitution of the alkali metal atom in the carboxyl group of 2PCA, a change in the charge distribution of electron on the carbon of the carboxyl group and the aromatic ring occurred (Fig. 6). An increase in the value of the electron charge with respect to the carboxylic acid group occurred on the oxygen atoms in the carboxylate anion of salts. A small increase in the value of electron charge was calculated by NBO (B3LYP/6-311++G**), for the nitrogen atoms in the pyrazine ring of 2PCA salts with respect to that of the ligand. The electronic charge on the carbon atoms No C2, C3 and C4 increases, while it decreases on the C1 atom. The changes in the charge values occur along the 2PCA–Li–Na–K series. The electronic charge on aromatic protons of lithium, sodium and potassium 2-pyrazinecarboxylates increases as compared with the ligand. Similar changes were observed in the experimental 1H-NMR spectra—chemical shifts were reduced in a series 2PCA–Li–Na–K–Rb–Cs, which implies the increasing values of electron density on the aromatic protons.

Fig. 6
figure 6

Electron charge distribution calculated by NBO in B3LYP/6-311++G** for 2-pyrazinecarboxylic (a) acid and lithium (b), sodium (c) and potassium (d) 2-pyrazinecarboxylates

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The electronic charge on nitrogen atoms in the pyrazine ring in lithium, sodium and potassium 2,3-pyrazinedicarboxylate increases significantly with respect to the ligand (Fig. 7). The values of electronic charge on the aromatic ring carbons of the 2,3PDCA salts also vary from the value for the ligand. These changes in the alkali metal 2,3-pyrazinedicarboxylates are greater than in the 2-pyrazinecarboxylates.

Fig. 7
figure 7

Electron charge distribution calculated by NBO in B3LYP/6-311++G** for 2,3-pyrazinedicarboxylic acid (a) and lithium (b), sodium (c) and potassium (d) 2,3-pyrazinedicarboxylates

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Conclusions

On the basis of experimental and theoretical calculations, it was found that:

  1. 1.

    Comparing the curves of the thermal decomposition of the alkali metal salt of studied acids one can conclude that salts of 2-pyrazinecarboxylic acid have a higher thermal stability than the salts of 2,3-pyrazinedicarboxylate.

  2. 2.

    Spectroscopic (IR, Raman and NMR) data showed that alkali metals disturb the electronic system of the aromatic ring of ligands, (of 2-pyrazinecarboxylate, and 2,3-pyrazinedicarboxylate). The degree of perturbation increases in the studied series salts in order: Li–Na–K–Rb–Cs.

  3. 3.

    Experimental studies showed that alkali metals to much greater extent impact on the electronic charge distribution of 2,3-pyrazinedikarboxylic than of 2-pyrazinecarboxylic acid.

  4. 4.

    Theoretical calculations (aromaticity index values, the charge distribution by NBO) performed for geometrically optimized structures confirm the results of experiments on the effect of alkali metals on the electron charge distribution of ligand.