Investigation of molecula structure - chirality relationship of ephedrine and pseudoephedrine drug using thermal analyses and mass spectrometry techniques combined with MO-calculations

Two diastercoisomers ephedra drugs namely; ephedrine [eph.] and pseudoephedrine [psi-eph.] hydrochloride, have been investigated for their chirality using thermal analysis [TA] measurement [TG/DTA] and electron ionization mass spectrometry [EI-MS] at 70 eV. Monte Carlo conformational search technique was used for exploration of conformational space of ephedrine and psi-eph., using Amber force field molecular mechanics method. MO-calculations were performed using semi-empirical PM3 procedure on the obtained conformational sample for investigation of the different molecular properties. The calculations include bond length, bond order, charge distribution, ionization energy and heat of formation, in neutral and positively charged forms for the two drugs. The effect of diastereoisomerism on thermal analysis decomposition behavior of these drugs was studied. The obtained data confirmed the chirality and declared the structure reactivity relationship of these drugs

Structure investigation of piroxicam and tenoxicam using thermal analyses, mass spectrometry and semi-empirical MO calculations

Steroidal and non-steroidal anti-inflammatory agents such as oxicam group [e.g. piroxicam [Pir] and tenoxicam [Ten] were investigated using thermal analyses [TA] measurements [TGA, DTGA, DTA and DDTA] in comparison with El mass spectral [MS] fragmentation at 70 eV. Semi-emperical molecular orbital [MO] calculations have been carried out using PM3 described by Stewart on Pir and Ten both as neutral molecules and the corresponding positively charged molecular ions. These calculations included molecular geometries such as bond length, bond order, bond strain, atomic charge distribution and hybridization, and heat of formation of these drugs. Thermal analyses reveal a high response of Pir and Ten to temperature variation with a cleavage of six bonds in aliphatic side chains around O, S, and N heteroatom, leaving aromatic radicals as final products, which become volatile at high temperature. TA mostly involved fragmentation of SO2 gas molecule at first followed by C, N, and O containing fragments as CH3CN, CHO, NHCONHCO, and NHCO. The MS fragmentations indicate the presence of the same final products as given by TA technique. Mass fragmentation pathways refer to the loss of more or less the same fragments via cleavage of seven bonds of Pir and nine bonds of Ten molecular ions, in parallel and many consecutive steps as explained by geometries values calculated by MOC. These may refer to the instability of Pir and Ten molecular ions in comparison with their neutral forms. This instability is explained by comparison of the calculated partial charges on their atoms and/or their heat of formation values. The best pathway in both TA and MS techniques is that starts with the loss of SO2 gas molecule and followed by the loss of HCO and CH3CN molecules. The partial charge values and the stereo structures of ionic and neutral form refer to a distinct phenomenon of collection of voluminous charge density on SO2 group covering in space most atoms behind. It is explained by the highest electron withdrawing abilities of the heteroatom, two O and S in this group as a result of their high electro negativities. This rationalized the starting of fragmentation process in TA and MS with the loss of SO2 gas molecules. Therefore, a MOC was applied to declare both TA and MS observations

Investigation of malonanilide and its dinitro-isomers using thermal analyses, mass spectrometry and semi-empirical MO calculation

In this paper malonanilide compound [M 1], and its dinitro-isomers [M 2 - M 4] compounds were investigated. The evaluation has been performed using thermal analyses [TA] measurements in comparison with electron ionization [EI] mass spectral [MS] fragmentation. Knowledge gained from experimental work was combined with theoretical calculations for neutral molecules, using the Modified Neglect of Diatomic Overlap [MNDO] semi-empirical MO calculations. The theoretical calculations include molecular geometry, bond order, charge distribution and heats of formation. For all the studied compounds, the major fragmentation pathways in TA and MS [including intermediates] is a CO-CH 2 bond rupture, followed by ketene [COCH 2] loss to form the nitroaniline structure. The MNDO procedure provides a basis for fine distinction among sites of initial bond cleavage, which is crucial to the rationalization of subsequent fragmentation of the molecule. Also, the thermal behavior decomposition due to ortho effect for o,o-dinitromalonanilide is discussed in terms of experimental and the MO calculations