Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
Molecular structure and spectroscopic analysis of homovanillic acid and its sodium salt – NMR, FT-IR and DFT studies
Graphical abstract
Molecular electrostatic potential map (MEP) for homovanillic acid and sodium homovanillate.
Introduction
Homovanillic acid or 4-hydroxy-3-methoxyphenylacetic acid (HVA) has been investigated by various researches because of its biological activities. It is metabolite of dopamine one of the catecholamines, which are important natural molecules containing a catechol ring, which act as neurotransmitters or hormones [1]. HVA concentrations in human plasma are often employed in routine clinical examinations to assess dopamine metabolism in order to find the relation between kind of metabolite in plasma and different parameters of aggression. Several methods were used to determine such metabolites. Raggi et al. analyzed real plasma samples from volunteers under experimentally induced psychological stress using HPLC determination [2]. Symptoms associated with low urinary level of HVA include depression, sleep disturbances, anxiety and fatigue. Assessment of this metabolite in urine may serve as a useful indicator of early exposure to urban pollutants. Homovanillic acid due to its structure with several functional groups and its clinical importance as a neurotransmitter metabolism marker was chosen as template for investigation by Dineiro et al. [3]. They examined the formation of complexes between the template and the two monomers methacrylic and 2-trifluoromethacrylic acids as possible functional monomers for the imprinting of homovanillic acid. Molecularly imprinted polymers have remarkable recognition properties of great interest in a range of applications from an analytical point of view [3]. According to Luliński et al. HVA could be marker in the bioanalysis of catecholamines [4]. Small organic acids play an important role, because of they able to interact and/or penetrate biological membranes [5]. These interactions are dependent on their structure. Molecular structure of 4-hydroxy-3-methoxyphenylacetic acid was determined earlier by Okabe et al. [6]. As observed in catecholamines the HVA molecule has the carboxyl side chain oriented perpendicular to the phenyl-ring plane. Homovanillic acid molecules form a dimer with hydrogen bond between the carboxyl groups. Some data of spectroscopic and computational analyses of HVA were given by Förner and Badawi [7]. They reported molecular structure parameters obtained using DFT-B3LYP and ab initio MP2 methods with the 6-311G** basis set. HVA was described as molecule with non-planar structure in which OH and OMe groups attached to the aromatic ring are coplanar with the ring (COH and COC bond systems are in the same plane as the aromatic ring), because a stabilizing hyperconjugation interaction between the aromatic π system of the ring and the lone pairs of the oxygen atoms can take place. The vibrational assignments of the normal modes were made on the basis of normal-coordinate analysis and the calculated and experimental IR and Raman spectra [7]. Authors compared obtained results with their previous data of phenylacetic acid molecule as parent compound [8].
Phenylacetic acid and alkali metal phenylacetates were also the subject of our previous research [9]. In this paper the influence of sodium ion on molecular structure of free homovanillic acid is studied. The assessment of the electronic charge distribution in sodium 4-hydroxy-3-methoxyphenylacetate molecule will let to predict the kind of deformation of the electronic system of acid molecule occurring under the influence of metal. It will also permit to make more precise interpretation of mechanism by which sodium affects the biochemical properties of homovanillic acid.
Section snippets
Experimental
Homovanillic acid (from Acros Organic) was used without further purification. Sodium homovanillate was prepared by dissolving the powder of homovanillic acid in the water solution of sodium hydroxide (Aldrich) in a stoichiometric ratio. The mixed solution was slowly condensed at 70 °C to about 30% of starting volume. Then the solution was left at the room temperature for 24–48 h until the sample crystallized in the solid-state. The remaining solvent was removed by drying under reduced pressure at
Calculated geometrical structure
The density functional hybrid method B3LYP with 6-311++G** basis set was used to calculate optimized geometrical structures of studied compounds. Ten various structures of homovanillic acid were taken into account. Energies (in kJ/mol) of analyzed conformations of homovanillic acid related to the conformation I (of the lowest energy) are presented in Fig. 1, the corresponding values of dipole moment are shown in Fig. S1 (in Supplementary material). The bond lengths and the angles between bonds
Conclusions
The spectroscopic characteristic (NMR IR and Raman spectra) for homovanillic acid and sodium homovanillate was done. Good correlation between experimental and theoretical IR, 1H and 13C NMR spectra was noticed. In IR and Raman spectra different changes of bands were observed. The intensity and wavenumbers in sodium homovanillate spectra in the case of bands numbered as 1, 8b, 16b, 19a decrease in comparison to homovanillic acid, which shows disorder of the electron ligand. The chemical shifts
Acknowledgement
The project was funded by the National Science Center awarded by decision number DEC-2011/01/B/NZ9/06830.
References (25)
- et al.
J. Chromatogr. B
(1999) - et al.
Biosens. Bioelectron.
(2006) - et al.
J. Mol. Struct.
(2008) - et al.
Spectrochim. Acta A
(2011) - et al.
J. Mol. Struct.
(2013) - et al.
J. Mol. Struct. THEOCHEM.
(2006) - et al.
Tetrahedron
(2000) - et al.
Computational Chemistry and Molecular Modeling: Principle and Applications
(2008) - et al.
J. Chem. Phys.
(1993) - et al.
Magn. Reson. Chem.
(2007)
J. Sep. Sci.
Polym. Int.
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