Batrachotoxin time-resolved absorption and resonance FT-IR and raman biospectroscopy and density functional theory (DFT) investigation of vibronic-mode coupling structure in vibrational spectra analysis: A spectroscopic study on an anti-gum cancer drug

Gum cancers are cancers that arise from the gum. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of gum cancers: basal-cell gum cancer (BCC), squamous-cell gum cancer (SCC) and melanoma. Batrachotoxin (BTX) is an anti-gum cancer extremely potent cardiotoxic and neurotoxic steroidal alkaloid found in certain species of beetles, birds, and frogs. Batrachotoxin was derived from the Greek word βάτραχος bátrachos "frog". StructurallyAbstract


Introduction
Gum cancers are cancers that arise from the gum. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of gum cancers: basal-cell gum cancer (BCC), squamous-cell gum cancer (SCC) and melanoma. Batrachotoxin (BTX) is an anti-gum cancer extremely potent cardiotoxic and neurotoxic steroidal alkaloid found in certain species of beetles, birds, and frogs. Batrachotoxin was derived from the Greek word βάτραχος bátrachos "frog". Structurally-related chemical compounds are often referred to collectively as batrachotoxins. It is an extremely poisonous alkaloid. In certain frogs this alkaloid is present mostly on the gum. Such frogs are among those used for poisoning darts. Batrachotoxin binds to and irreversibly opens the sodium channels of nerve cells and prevents them from closing, resulting in paralysis-no antidote is known. Density Functional Theory (DFT) is one of the most powerful calculation methods for electronic structures [5][6][7]. Numerous results have been previously studied and indicate successful use of these methods [8][9][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][12][13][14][15][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 .

Details of calculations
All calculations of molecular orbital in the base of ab are performed by Gaussian 09. In calculation process, the structure of Batrachotoxin 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 are 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 399 (K).
C-H stretching vibrations in single replacement of benzene cycles are usually seen in band range of 3203-3453 cm -1 . Weak Raman bands are at 3192 cm -1 and 3205 cm -1 . C-C stretching mode is a strong Raman mode at 1202 cm -1 . Raman weak band is seen at 1676 cm -1 , too. Bending mode of C-H is emerged as a weak mode at 1401 cm -1 and 1200 cm -1 and a strong band at 1284 cm -1 in Raman spectrum. Raman is considerably active in the range of 1203-1453 cm -1 which 1196 cm -1 indicates this issue.
C-H skew-symmetric stretching mode of methylene group is expected at 3188 cm -1 and its symmetric mode is expected at 3002 cm -1 . Skew-symmetric stretching mode of CH 2 in Batrachotoxin has a mode in mid-range of Raman spectrum at 3103-3223 cm -1 . When this mode is symmetric, it is at 3098 cm -1 and is sharp. The calculated wavenumbers of higher modes are at 3066 cm -1 and 3096 cm -1 for symmetric and skew-symmetric stretching mode of methylene, respectively.
Scissoring vibrations of CH 2 are usually seen at the range of 1530-1584 cm -1 which often includes mid-range bands. Weak bands at 1543 cm -1 are scissoring modes of CH 2 in Raman spectrum. Moving vibrations of methylene are usually seen at 1472 cm -1 . For the investigated chemical in the current study, these vibrations are at 1342 cm -1 were calculated using density functional theory. Twisting and rocking vibrations of CH 2 are seen in Raman spectrum at 918 cm -1 and 1191 cm -1 , respectively, which are in good accordance with the results at 902 cm -1 and 1167 cm -1 , respectively.
In a non-ionized carboxyl group (COOH), stretching vibrations of carbonyl [C=O] are mainly observed at the range of 1843-1891 cm -1 . If dimer is considered as an intact constituent, two stretching vibrations of carbonyl for symmetric stretching are at 1743-1788 cm -1 in Raman spectrum. In the current paper, stretching vibration of carbonyl mode is at 1800 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 1370 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 1050 cm -1 of Raman spectrum. The stretching mode of C-O (H) emerges as a mid-band of Raman spectrum at 1250 cm -1 .  Heidari A (2019) Batrachotoxin time-resolved absorption and resonance FT-IR and raman biospectroscopy and density functional theory (DFT) investigation of vibronic-mode coupling structure in vibrational spectra analysis: A spectroscopic study on an anti-gum cancer drug

Conclusion and summary
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 Batrachotoxin. 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.  Heidari A (2019) Batrachotoxin time-resolved absorption and resonance FT-IR and raman biospectroscopy and density functional theory (DFT) investigation of vibronic-mode coupling structure in vibrational spectra analysis: A spectroscopic study on an anti-gum cancer drug  (1)