Vibrational Spectra of [(3-chloro phenyl) Piprazine 1-yl]-3-[oxy (3-acetamidazole Phenyl) Propane]: A Highly Potent Hypertensive Drug

INTRODUCTION

(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania.Chemical Formula of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) isC23H29N3O2S2Tiotixene acts primarily as a highly potent antagonist of the dopamine D2 and D3 receptors (subnanomolar affinity). It is also an antagonist of the histamine H1, α1-adrenergic, and serotonin 5-HT7 receptors (low nanomolar affinity), as well as of various other receptors to a much lesser extent (lower affinity). It does not have any anticholinergicactivity.[3] Antagonism of the D2 receptor is thought to be responsible for the antipsychotic effects of tiotixene. Thiothixene is a thioxanthine used as an antipsychotic agent. Its effects are similar to the phenothiazine antipsychotics. Thiothixene is a thioxanthene derivative and a dopamine antagonist with antipsychotic property. Thiothixene blocks postsynaptic dopamine receptors in the mesolimbic system and medullary chemoreceptor trigger zone, thereby decreasing dopamine activity leading to decreased stimulation of the vomiting center and psychotic effects, such as hallucinations and delusions. In addition, this agent blocks the D2 somatodendritic autoreceptor, thereby increasing dopamine turnover. Thiothixene possesses weak affinity for the histamine H1 and alpha-adrenergic receptors. Dual action hypotheses have suggested that antipsychotic compounds may show a stimulating effect at low doses and an antipsychotic effect at higher doses. The clinical literature of thiothixene in adult schizophrenic patients was reviewed in an attempt to correlate optimal dose with chosen indices of the dual action hypothesis. Activation and side effects of CNS stimulation correlated highly with each other and with dosage; a significant negative regression line on optimal dose was seen. Overall efficacy did not correlate with dosage or with activation-stimulation, but showed the presence of an antipsychotic component at least equal to standard antipsychotics. The method employed seems Antipsychotics, also known as neuroleptics or major tranquilizers, are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. They are increasingly being used in the management of non-psychotic disorders. Antipsychotics are usually effective in relieving symptoms of psychosis in the short term. Psychosis is an abnormal condition of the mind that results in difficulties telling what is real and what is not. Symptoms may include false beliefs and seeing or hearing things that others do not see or hear. Other symptoms may include incoherent speech and behavior that is inappropriate for the situation. There may also be sleep problems, social withdrawal, lack of motivation, and difficulties carrying out daily activities.Antipsychotic drugs such as haloperidol and chlorpromazine tend to block dopamine D2 receptors in the dopaminergic pathways of the brain. This means that dopamine released in these pathways has less effect. (9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) using Gauss view program packages at the Becke3-Lee-Yang-Parr (B3LYP) level with standard 6-31G basis set.DFT computational codes are used in practise to investigate the structural, magnetic and electronic properties of molecules, materials and defects. DFT calculations allow the prediction and calculation of material behaviour on the basis of quantum mechanical considerations, without requiring higher order parameters such as fundamental material properties. DFT computational methods are applied for the study of systems to synthesis and processing parameters. In such systems, experimental studies are often encumbered by inconsistent results and non-equilibrium conditions. Examples of contemporary DFT applications include studying the effects of dopants on phase transformation behaviour in oxides, magnetic behaviour in dilute magnetic semiconductor materials.

DFT is supported by many quantum chemistry and solid state physics software packages, often along with other methods.Optimized geometrical structure of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene);

The vibrational frequencies of the solid phase FT-IR and FT-Raman spectra of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) were recorded in the regions 3500-500 and 3500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) were obtained by the Restricted Hartree-Fock (RHF) density functional theory (DFT) with complete relaxation in the potential energy surface using 6-31G basis set. The harmonic vibrational frequencies for(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) were calculated and the scaled values have been compared with experimental values of FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The harmonic vibrational wave numbers and intensities of vibrational bands of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) with its cation and anion were calculated and compared with the neutralThiothixene. The DFT calculated HOMO and LUMO energies shows that charge transfer occurs within the molecule. DFT calculations allow the prediction and calculation of material behavior on the basis of quantum mechanical considerations, without requiring higher order parameters such as fundamental material properties.

Infrared and Raman spectra of different crystalline forms of the same organic compound can be used to identify a pure crystal form and quantify a mixture of two forms. Many organic compounds have one or more crystalline or polymorphic forms. The observed differences in the spectra of different polymorphs include changes in frequencies, relative intensities, band contours and the number of bands.The IR and Raman spectra of (9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) an antipsychotics compound have been computed performing density functional theory calculations at the B3LYP/6‐31G(d) level of theory. In Vibrational spectroscopy the infrared and Raman spectra of optimized geometrical structure of pharmaceutical

of intensities. Then the following figures show the calculated IR and Raman spectra of Optimized geometrical structure(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide(Thiothixene) .These calculations were done by using B3LYP/6˗31G methods.

Dipole moment, the measure of the electrical polarity of a system of chargesThe electric dipole moment is a measure of the separation of positive and negative electrical charges within a system, that is, a measure of the system's overall polarity.Bond dipole moment of Optimized geometrical structural compound is the measurement of polarity of a chemical bond and also known as the mathematical product of the separation of the ends of a dipole and the magnitude of the charges. The dipole moment creates by unequal sharing of electron in optimized geometrical molecules by their atoms. Dipole moment and energy of the medically active compound[(3-chloro phenyl) piprazine 1-yl]-3-[oxy (3-acetamidazole phenyl) propane] is shown in following table:- (1 Debye = 3.34*10-30 cm.) (1 a.u. of energy = 1hartree = 4.360 × 10−18 J. = 27.211eV = 2625kJ/mol = 627.5kcal/mol.)

The most important orbitals in a molecule are the frontier molecular orbitals, called highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO).These orbitals determine the way the molecule interacts with other species. The frontier orbital gap helps characterize the chemical reactivity and kinetic stability of the molecule. A molecule with a small frontier orbital gap HOMO and LUMO are types of molecular orbitals. The acronyms stand for "highest occupied molecular orbital" and "lowest unoccupied molecular orbital", respectively. The energy difference between the HOMO and LUMO is termed the HOMO–LUMOgap. HOMO and LUMO are sometimes called frontier orbitalsin frontier molecular orbital theory. The difference in energy between these two frontier orbitals can be used to predict the strength and stability of transition metal complexes, as well as the colors they produce in solution. Energy levels of the frontier molecular orbital‘s especially HOMO, LUMO as well as their spatial distributions are important parameters for determining the optoelectronic properties. The density plot of the HOMO and LUMO of(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide (Thiothixene) is calculated at B3LYP/6-31G level of theory and are shown in Figure;

The energy gap between HOMO and LUMO has been used to prove the bioactivity from intramolecular charge transfer. The energy gap measures the kinetic stability of the molecules. The The HOMO and LUMO energy calculated by B3LYP /6-31G method as shown below in table:-

In molecular geometry, bond length or bond distance is the average distance between nuclei of two bonded atoms in a molecule. It is a transferable property of a bond between atoms of fixed types, relatively independent of the rest of the molecule. Molecular geometries can be specified in terms of bondlengths, bond angles and torsional angles. The bond length is defined to be the average distance between the nuclei of two atoms bonded together in any given molecule. A bond angleis the angle formed between three atoms across at least two bonds. The such as bond lengths, bond angle are the optimized structural parameters , so these parameters were determined at B3LYP level theory with 6-31G basis set and they are presented in a table, which is given below –

C12-C11 1.51816 C11-O16 1.24664

H13-C12-H14 107.697 O16-C11-N9 123.027 C3-C4-H7 119.556 H58-C55-C2 111.611

C4-C5-H8 120.453 C2-C1-C6 119.179 S17-C18-H19 107.241 C21-C24-H26 109.164 H40-C39-N37 108.632 C42-N38-C48 113.035 H47-C45-N37 108.630 N38-C27-C29 120.829 Cl59-C30-C28 117.785 H36-C34-C32 121.700 C29-C32-C34 121.394

Thus, the Simulation report of[(3-chloro phenyl) piprazine 1-yl]-3-[oxy (3-acetamidazole phenyl) propaneis on progress. It will be reported very soon.

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Micromolecular and Biophysics Laboratory, Department Of Physics, Dr. Shakuntala Mishra National and Rehabilitation University, Mohan Road, Lucknow