Okadaic acid, C44H68O13, is a toxin produced by several species of dinoflagellates, and is known to accumulate in both marine sponges and shellfish. One of the primary causes of diarrhetic shellfish poisoning, Okadaic acid is a potent inhibitor of specific protein phosphatases and is known to have a variety of negative effects on cells. A polyketide, polyether derivative of a C38 fatty acid, Okadaic acid and other members of its family have shined light upon many biological processes both with respect to dinoflagellate polyketide synthesis as well as the role of protein phosphatases in cell growth. Parameters such as FT-IR and Raman vibrational wavelengths and intensities for single crystal Okadaic Acid are calculated using density functional theory and were compared with empirical results. The investigation about vibrational spectrum of cycle dimers in crystal with carboxyl groups from each molecule of acid was shown that it leads to create Hydrogen bonds for adjacent molecules. The current study aimed to investigate the possibility of simulating the empirical values. Analysis of vibrational spectrum of Okadaic Acid is performed based on theoretical simulation and FT-IR empirical spectrum and Raman empirical spectrum using density functional theory in levels of HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG**. Vibration modes of methylene, carboxyl acid and phenyl cycle are separately investigated. The obtained values confirm high accuracy and validity of results obtained from calculations [1-42].
Vibronic structure, Vibrational spectra analysis, Density Functional Theory (DFT), Okadaic acid, Non-Focal functions of becke, Correlation functions of Lee-Yang-Parr, Time-Resolved absorption and resonance, FT-IR and Raman biospectroscopy
Okadaic acid, C44H68O13, is a toxin produced by several species of dinoflagellates, and is known to accumulate in both marine sponges and shellfish. One of the primary causes of diarrhetic shellfish poisoning, Okadaic acid is a potent inhibitor of specific protein phosphatases and is known to have a variety of negative effects on cells. A polyketide, polyether derivative of a C38 fatty acid, Okadaic acid and other members of its family have shined light upon many biological processes both with respect to dinoflagellate polyketide synthesis as well as the role of protein phosphatases in cell growth. Density Functional Theory (DFT) is one of the most powerful calculation methods for electronic structures [5-7]. Numerous results have been previously studied and indicate successful use of these methods [8-10]. The theory is one of the most appropriate methods for simulating the vibrational wavenumbers, molecular structure as well as total energy. It may be useful to initially consider the calculated results by density functional theory using HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG** approach [11-16]. It should be noted that calculations are performed by considering one degree of quantum interference as well as polarization effects of 2d orbitals in interaction [17-47].
Okadaic acid is a tropical weed belonging to Toxins family. Amongst Toxins, Okadaic acid contains anti-fungal activity, acetylcholinesterase inhibitory activity, anti-oxidant activity [48-64], mast cell stabilization and membrane protection activity [65-92], anti-bacterial activity [93-127] and anti-cancer activity [128-145], anti-hyperglycemic an anti-hyperlipidemic effects [146-156] and anti-arthritic activity, immunomodulatory activity [157-173] and anti-diabetic activity [174-187]. Our earlier report stated that the Okadaic acid has high anti-oxidant activity [188-200]. The observations show that Okadaic acid can be used for pharmaceutical applications. In this view, Okadaic acid was taken and examined for its phytochemical and active principles in vitro anti-oxidant models and in silico approach for anti-histamine activity. Free radicals are atoms with unpaired electrons which can cause various diseases. Intake of vitamin E can reduce the problems associated with free radicals in the body [201-209]. The unpaired electrons of free-radical accumulation cause oxidative stress in the body. Oxidative stress causes cell damage leading to various health issues such as chronic disease, cancer, autoimmune disorders, aging, cataract, rheumatoid arthritis, cardiovascular diseases, neurodegenerative diseases, respiratory disorders [210-218] and also the induced oxidative stress causes bronchial contraction by the release of cyclooxygenase and lipoxygenase in the airway that leads to bronchial asthma in human [219-225]. Asthma is a chronic inflammatory lung disease that happens due to the respiratory infection triggered by the inhalation of allergens like tobacco smoke, air pollutants, genetic and environment factors [226-232] which leads to the release of histamine and leukotrienes from the mast cell in the lung. The high release of histamine due to allergic reactions is regulated by histamine H1 receptor [233-235]. Histamine affects the immune response and related functions in human through H1, H2, H3 and H4 receptors activation with their intracellular signals [236-238]. The present research work demonstrates the chemotaxonomy of such valuable plant, from the genus of Okadaic acid. In addition, pharmaceutical applications such as in vitro anti-oxidant and in silico anti-histamine activity of their active principles as natural remedy was examined.
All calculations of molecular orbital in the base of ab are performed by Gaussian 09. In calculation process, the structure of Okadaic Acid molecule (Figure 1) is optimized and FT-IR and Raman wavenumbers are calculated using HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG** base. All optimized structures are adjusted with minimum energy. Harmonic vibrational wavenumbers are calculated using second degree of derivation to adjust convergence on potential surface as good as possible and to evaluate vibrational energies at zero point. In optimized structures considered in the current study, virtual frequency modes are not observed which indicates that the minimum potential energy surface is correctly chosen. The optimized geometry is calculated by minimizing the energy relative to all geometrical quantities without forcing any constraint on molecular symmetry. Calculations were performed by Gaussian 09. The current calculation is aimed to maximize structural optimization using density functional theory. The calculations of density functional theory is performed by HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG** function in which non-focal functions of Becke and correlation functions of Lee-Yang-Parr beyond the Franck-Condon approximation are used. After completion of optimization process, the second order derivation of energy is calculated as a function of core coordination and is investigated to evaluate whether the structure is accurately minimized. Vibrational frequencies used to simulate spectrums presented in the current study are derived from these second order derivatives. All calculations are performed for room temperature of 414 (K).
Analysis of vibrational spectrum of Okadaic Acid is performed based on theoretical simulation and FT-IR empirical spectrum and Raman empirical spectrum using density functional theory in levels of HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG**. Vibration modes of methylene, carboxyl acid and phenyl cycle are separately investigated.
C-H stretching vibrations in single replacement of benzene cycles are usually seen in band range of 3225-3475 cm-1. Weak Raman bands are at 3214 cm-1 and 3227 cm-1. C-C stretching mode is a strong Raman mode at 1199 cm-1. Raman weak band is seen at 1673 cm-1, too. Bending mode of C-H is emerged as a weak mode at 1423 cm-1 and 1222 cm-1 and a strong band at 1306 cm-1 in Raman spectrum. Raman is considerably active in the range of 1225-1475 cm-1 which 1218 cm-1 indicates this issue.
C-H skew-symmetric stretching mode of methylene group is expected at 3210 cm-1 and its symmetric mode is expected at 3024 cm-1. Skew-symmetric stretching mode of CH2 in Okadaic Acid has a mode in mid-range of Raman spectrum at 3125-3245 cm-1. When this mode is symmetric, it is at 3120 cm-1 and is sharp. The calculated wavenumbers of higher modes are at 3088 cm-1 and 3118 cm-1 for symmetric and skew-symmetric stretching mode of methylene, respectively.
Scissoring vibrations of CH2 are usually seen at the range of 1555-1606 cm-1 which often includes mid-range bands. Weak bands at 1565 cm-1 are scissoring modes of CH2 in Raman spectrum. Moving vibrations of methylene are usually seen at 1494 cm-1. For the investigated chemical in the current study, these vibrations are at 1364 cm-1 were calculated using density functional theory. Twisting and rocking vibrations of CH2 are seen in Raman spectrum at 940 cm-1 and 1214 cm-1, respectively, which are in good accordance with the results at 924 cm-1 and 1189 cm-1, respectively.
In a non-ionized carboxyl group (COOH), stretching vibrations of carbonyl [C=O] are mainly observed at the range of 1865-1913 cm-1. If dimer is considered as an intact constituent, two stretching vibrations of carbonyl for symmetric stretching are at 1765-1810 cm-1 in Raman spectrum. In the current paper, stretching vibration of carbonyl mode is at 1822 cm-1 which is a mid-range value.
Stretching and bending bands of hydroxyl can be identified by width and band intensity which in turn is dependent on bond length of Hydrogen. In dimer form of Hydrogen bond, stretching band of O-H is of a strong Raman peak at 1392 cm-1 which is due to in-plain metamorphosis mode. Out-of-plain mode of O-H group is a very strong mode of peak at 1074 cm-1 of Raman spectrum. The stretching mode of C-O (H) emerges as a mid-band of Raman spectrum at 1272 cm-1.
Lattice vibrations are usually seen at the range of 0-575 cm-1. These modes are induced by rotary and transferring vibrations of molecules and vibrations and are including Hydrogen bond. Bands with low wavenumbers of Hydrogen bond vibrations in FT-IR and Raman spectrum (Figure 2) are frequently weak, width and unsymmetrical. Rotary lattice vibrations are frequently stronger than transferring ones. Intra-molecular vibrations with low wavenumbers involving two-bands O-H …O dimer at 113 cm-1, 218 cm-1 and 274 cm-1 are attributed to a rotary moving of two molecules involving in-plain rotation of molecules against each other.
Calculations of density functional theory using HF/6-31G*, HF/6-31++G**, MP2/6-31G, MP2/6-31++G**, BLYP/6-31G, BLYP/6-31++G**, B3LYP/6-31G and B3LYP6-31-HEG** levels were used to obtain vibrational wavenumbers and intensities in single crystal of Okadaic Acid. Investigation and consideration of vibrational spectrum confirm the formation of dimer cycles in the investigated crystal with carboxyl groups from each Hydrogen molecule of acid protected from adjacent molecules. The calculated vibrational spectrum which obtains from calculations of density functional theory is in good accordance with recorded empirical values which indicates successful simulation of the problem. The obtained results indicate that the results obtained from theoretical calculations are valid through comparing with empirical recorded results.
Authors are supported by an American International Standards Institute (AISI) Future Fellowship Grant FT1201009373517. We acknowledge Ms. Isabelle Villena for instrumental support and Dr. Michael N. Cocchi for constructing graphical abstract figure. We gratefully acknowledge Prof. Dr. Christopher Brown for proofreading the manuscript.