الفهرس 
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Abstract
The present work includes a kinetic and mechanistic study of the interactions of Ninhydrin and vanillin with some drugs containing an amino group in their pharmaceutical composition.
CHAPTER I, Introduction.
It contains an introduction to the thesis and includes a discussion of the importance of both Ninhydrin and vanillin in the detection of ammonia or amines, and each of them is widely used as a chemical reaction intermediate in the identification of compounds of pharmacological interest applicable to kinetic studies. Our current study suggests the kinetics and mechanistics of the interaction of ninhydrin and vanillin with ampicillin, baclofen and tranexamic acid in their pharmaceutical formulations.
This chapter also contains definitions of:
1- Ampicillin is a β-lactam antibiotic agent for parenteral use, it is an important drug in clinical practice, considering that it is used in many parts of the world for treating a variety of infectious diseases, as well as being recommended by the World Health Organization.
2- Baclofen (4-amino-3-p-chlorophenyl butyric acid) is a chemical analogue of γ-amino butyric acid and is widely used as a skeletal muscle relaxant in the treatment of spastic disorders.
3- Tranexamic acid (Trans-4-(amino methyl) cyclo hexane carboxylic acid) is a antifibrinolytic drug that reduces menstrual blood loss and is a possible alternative to surgery in menorrhagia, and has been used successfully to control bleeding in pregnancy.
CHAPTER II, Experimental.
It contains the chemicals, the preparation of the solutions used, the methods of preparation, as well as the method used for the kinetic and mechanical study. It also contains the methods used to analyze the results, as well as the laboratory equipment used in the study.
CHAPTER III, Results and discussion.
It contains and discusses the results, including the effect of various factors on the rate of reactions. This chapter consists of six parts:
Part (1)
The kinetics of Nin reaction with Amp has been studied in an aqueous acidic medium. The product of the reaction was examined spectroscopically using Nuclear magnetic resonance (1H-NMR) and Infrared spectra in addition to Ultra-performance liquid chromatography (UPLC). The reaction was monitored spectrophotometrically, with (0.1- 0.4) × 10-4 mol dm-3 of [Amp], (0.5-5.0) ×10-2 mol dm-3 [Nin] and (0.2 - 1.0) mol dm-3 ionic strength (I) over the (30-50) °C range of temperature. It is first order with respect to [Nin] and [Amp], decreases as pH increases in the range (4.70-6.04). The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The rate of the reaction follows the rate law d[Amp-Nin]/dt ={(k3+k2[H+])[Nin]}×[Amp].
Part (2)
Kinetics of the reaction of Nin with Bac has been studied spectrophotometrically in an aqueous acidic medium under pseudo order conditions over (30-50) oC range, (0.1- 0.4) × 10-4 mol dm-3 of [Bac], (0.5-5.0) ×10-2 mol dm-3 [Nin] and ionic strength (0.2 - 1.0) mol dm-3. The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The UV–visible spectroscopic measurements were carried out to confirm the coupling between Nin and Bac. The reaction is first order with respect to [Nin] and [Bac], decreases as pH increases in the range (3.90-5.06). The experimental rate law is consistent with a mechanism in which the protonated and deprotonated form of Nin are involved in the rate-determining step and the deprotonated species is the more reactive one. The product of the reaction was examined spectroscopically using nuclear magnetic resonance (1H-NMR) and infrared spectra (IR) in addition to an ultra-performance liquid chromatograph (UPLC). Density functional theory (DFT) was performed to search the geometries of the final product result from the reaction between Nin and Bac. Also, enthalpy of the reaction was calculated theoretically with DFT. Interaction region indicator (IRI) calculations is used to reveal chemical bonding and weak interaction in the coupled compound of Bac-Nin.
Part (3)
Reaction of Nin with TA has been studied kinetically in aqueous acidic medium. The product of the reaction was examined spectroscopically using Nuclear magnetic resonance (1H-NMR) and Infrared spectra in addition to Ultra-performance liquid chromatograph (UPLC). The reaction was monitored spectrophotometrically, with (0.1- 0.4) × 10-4 mol dm-3 of [TA], (0.5-5.0) ×10-2 mol dm-3 [Nin] and (0.2 - 1.0) mol dm-3 ionic strength (I) over the (35-55) oC range of temperature. It is first order with respect to [Nin] and [TA], decreases as pH increases in the range (4.50-5.63). An effect of catalyst on the rate of the reaction was studied. The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The rate of the reaction obeys the rate law d[TA-Nin]/dt ={k2 + (k4+k3[H+])[Nin]}×[TA]. The experimental rate law is consistent with a mechanism in which the protonated beside and unprotonated form of Nin are involved in the rate-determining step and the unprotonated species is the more reactive one. A for this reaction is the proposed mechanism was supported by an excellent isokinetic relationship between ∆H* and ∆S* for some Nin reactions.
Part (4)
The reaction of Van with Amp has been studied kinetically in an aqueous acidic medium. The product of the reaction was examined spectroscopically using Nuclear magnetic resonance (1H-NMR, 13C-NMR) and Infrared spectra in addition to Ultra-performance liquid chromatography (UPLC). The reaction was monitored spectrophotometrically, with (0.1-0.4)×10-4 mol dm-3 of [Amp], (0.5-5.0) ×10-2 mol dm-3 [Van] and (0.2 - 1.0) mol dm-3 ionic strength (I) over the (35-55) oC range of temperature. It is first order with respect to [Van] and [Amp], decreases as pH increases in the range (3.25-4.20). The effect of catalyst on the rate of the reaction was studied. The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The rate of the reaction obeys the rate law d[Amp-Van]/dt ={k2 + (k4+k3[H+])[Van]}×[Amp].
Part (5)
The reaction of Van with Bac has been studied kinetically in an aqueous acidic medium. The product of the reaction was examined spectroscopically using Nuclear magnetic resonance (1H-NMR, 13C-NMR) and Infrared spectra in addition to Ultra-performance liquid chromatography (UPLC). The reaction was monitored spectrophotometrically, with (0.1-0.4)×10-4 mol dm-3 of [Bac], (0.5-5.0) ×10-2 mol dm-3 [Van] and (0.2 - 1.0) mol dm-3 ionic strength (I) over the (40-60) oC range of temperature. It is first order with respect to [Van] and [Bac], decreases as pH increases in the range (3.60-4.66). The effect of catalyst on the rate of the reaction was studied. The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The rate of the reaction obeys the rate law d[Bac-Van]/dt = {k2 + (k4+k3[H+]) [Van]} ×[Bac].
Part (6)
The reaction of Van with TA has been studied kinetically in an aqueous acidic medium. The product of the reaction was examined spectroscopically using Nuclear magnetic resonance (1H-NMR, 13C-NMR) and Infrared spectra in addition to Ultra-performance liquid chromatography (UPLC). The reaction was monitored spectrophotometrically, with (0.1- 0.4) × 10-4 mol dm-3 of [TA], (0.5-5.0) ×10-2 mol dm-3 [Van] and (0.2 - 1.0) mol dm-3 ionic strength (I) over the (40-60) oC range of temperature. It is first order with respect to [Van] and [TA], decreases as pH increases in the range (3.12-4.26). The thermodynamics activation parameters involving ∆H* and ∆S* have been calculated. The rate of the reaction obeys the rate law d[TA-Van]/dt ={(k3+k2[H+]) [Van]} ×[TA].