Thesis submitted for the Degree of Doctor of Medicine in the University of the Witwatersrand, Johannesburg / The interest of the biochemist in para-aminobenzoic acid is very recent and, indeed, only goes back about five years, but in this time quite a voluminous literature has accumulated on the biological aspects and importance of this aniline derivative. Attention was originally focussed on it indirectly as a result of the intensive research devoted to the understanding of the mode of action of the various sulphonamides, which were shown during the last decade to be very powerful chemothera-peutic agents against many bacteria. Fildes (1940, propounded the hypothesis that p-aminobenzoic acid was an essential meta-bolite for bacteria, that it was normally associated with an enzyme system in the bacterial cell, and that sulphanilamide, being structurally similar to p-aminobenzoic acid, was capable in sufficient concentration of displacing p-aminobenzoic acid from its enzyme and stopping this essential line of metabolism. Fildes further suggested that a substance which was found to be an essential metabolite for bacteria would also be essential in the animal kingdom, so that such a substance might be found to act as a vitamin in the higher animals and even in man. In 19U1 interest in p-aminobenzoic acid was intensified with the announcement by Ansbacher (19U1J that p-eminobenzoic acid was actually a vitamin and should be included in the vita¬min B complex. In this thesis, studies on the absorption and excretion of p-aminobenzoic acid are reported, the estimation of p-amino- bensoic acid being based on its property of antagonising the Bulphonamides. Evidence is presented that p-arainobenzoic acid la excreted ae p-acetylaminobenzoic acid, and that its conjuga- tion with the acetyl radical probably takeB place in the liver. Further it is suggested that the experiments performed do not lend support to the view that p-aminobenzolc acid is a vitamin for man. Finally the various physiological effects of p-aminobenzoic acid are discussed and an attempt is made to gauge its function in the living organism. Preliminary experiments indicating a new, hitherto unreported, role of p-aminobenzoic acid are re¬corded, namely its ability in large doses to increase the re¬sistance of animals to disease. / IT2017

No / Investigations of structural reactivity, molecular interactions and vibrational characterization of pharmaceutical drugs are helpful in understanding their behaviour. The aim of this study is to determine the molecular, electronic and chemical properties of the antibiotic drug nitrofurantoin (NF), after cocrystallisation with 3-aminobenzoic acid (3ABA) and to understand how those changes lead to variation of properties in the cocrystal NF–3ABA. NF–3ABA formation is explained by stabilization via the hydrogen-bond network between NF and 3ABA molecules. It is thoroughly characterized by IR, Raman and CP-MAS solid-state 13C NMR techniques, along with quantum chemical calculations. The results of IR, Raman, and 13C NMR analyses showed that imide N–H23 and C12[double bond, length as m-dash]O of NF interact with the acid C[double bond, length as m-dash]O and –OH groups in 3-ABA, respectively. Therefore the IR, Raman, and 13C NMR spectra verified the formation of N–H⋯O and O–H⋯O hydrogen bonds. To study hydrogen bonding interactions theoretically in NF–3ABA, two functionals B3LYP and wB97X-D have been used. A comparison is made between the results obtained by B3LYP and those predicted at the wB97X-D level. It is found that wB97X-D is best applied density functional theory (DFT) functional to describe the hydrogen bonding interactions. The strength and nature of hydrogen bonding in NF–3ABA have been analysed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. To validate the results obtained by QTAIM theory and to study the long-range forces, such as van der Waals interactions, the steric effects in NF–3ABA, the reduced density gradient (RDG) and the isosurface have been plotted using Multiwfn software. QTAIM and isosurface analysis suggested that the hydrogen bonding interactions present in NF–3ABA are moderate in nature. The calculated HOMO–LUMO energy gap shows that NF–3ABA is more active than NF and 3ABA. Chemical reactivity descriptors are calculated to understand the various aspects of pharmacological sciences. Chemical reactivity parameters show that NF–3ABA is softer and chemically more reactive than NF. The results suggest that cocrystals can be a feasible alternative for positively changing the targeted physicochemical properties of an active pharmaceutical ingredient (API). / Royal Society of Chemistry for the mobility grant (2015/17); DST (New Delhi) under the DST purse programme; UGC under the BSR meritorious fellowship scheme; DST, India under the Indo-Brazil project

Controlling crystal polymorphism, the ability of a molecule to crystallise in different solid forms, is one of the grand, ongoing challenges in materials science. In the pharmaceutical industry particularly, where up to half of the active pharmaceutical active ingredients exhibit polymorphic behaviour, it is of paramount importance to rationalise the impact of experimental conditions, such as the nature of the solvent, on the obtainment of a specific c crystal form. As strategies for the selection of polymorphs is still, by and large, based on a trial-and-error approach, it is necessary to acquire a fundamental understanding of the factors controlling the formation of a speci fic solid-state structure during crystallisation from solution. During this doctoral research project, we have conducted a computer simulation study of the early stages of crystallisation of meta-aminobenzoic acid, an important model system in the investigation of polymorphic phenomena. This molecule can in fact form five different polymorphic forms whose selective crystallisation from solution chiefly depends on the nature of the solvent. Molecular models and computational chemistry methods, based on density functional theory and molecular dynamics, have been developed and applied to quantify the processes surrounding the crystallisation of meta-aminobenzoic acid: solvent-solute separation, solute aggregation and surface reactivity. The aim was to identify what controls, at the molecular level, the polymorphic selection process during crystallisation from solution of this important active pharmaceutical ingredient. The results show that the solvent play a signi cant role during the key stages of meta-aminobenzoic acid crystallisation by controlling both the kinetics and thermodynamics of solute desolvation, formation of prenucleation clusters and surface reactivity. This work represents a paradigm of the role of molecular processes during the early stages of nucleation in affecting polymorph selection during crystallisation from solution.

No description available.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...

In organic-inorganic hybrid compounds an organic and an inorganic component are combined to form either a coordination or an ionic material. Relevant to the current study are hybrid materials composed of an organic part that contains one or more functional groups, for example amine, amide or carboxylic acid functional groups, and a metal halide inorganic portion. These functional materials display a range of interesting and desired properties, as evidenced from numerous literature reports on their properties. In order to utilise these properties in applications, a detailed understanding of the way that the crystal structure influences the properties of a material is required. However, before this step can be achieved, it is necessary to obtain information on the structural trends of the materials, and to use the approach of crystal engineering to identify robust supramolecular synthons that may afford structural control and prediction. The aim of the current study was to investigate the synthesis and crystal structures of hybrid materials, both ionic and coordination, composed of divalent transition metal halides and the organic components 4-aminobenzoic acid, 4-aminobenzamide and isonicotinic acid, and to identify the structural trends and crystal engineering synthons displayed by these materials. A secondary objective was the preliminary identification of properties exhibited by selected materials, in order to decide on the suitability of the materials for detailed future property investigations. Part of the work describes the investigation of the structural characteristics of coordination materials prepared by the combination of the organic and inorganic components. Five novel crystal structures of coordination materials were determined, and these are compared with six related coordination structures reported in the literature. Two of the novel structures display interesting one-dimensional coordination polymers, one of which has never been reported previously in the literature. The molecular and structural characteristics of both the novel and the literature coordination structures are presented in detail, and this discussion includes a description of the coordination geometry, the molecular geometry, packing trends, hydrogen bonding interactions and aromatic interactions. A comparison study across the three families of organic components in which the structural trends, hydrogen bonding interactions, aromatic interactions, ligand geometry and coordination modes are compared, is included. The results of the synthesis of the coordination materials by means of a mechanochemical method are presented, and the products afforded by this method are compared with those prepared via solution crystallisation. Finally, the results of preliminary studies of the thermal and electronic propertries of the materials are presented and interpreted. The combination of the hybrid components as cations and anions to form ionic materials yielded nine novel structures, and these were compared with five related ionic structures reported in the literature. The novel structures include three polar structures that contain the 4-ammoniumbenzamide cation, and to our knowledge no structures containing this cation have ever been reported in the literature, hence a significant contribution to the structural knowledge of perhalometallate salts of 4-ammoniumbenzamide is made by this study. In addition two novel structures display interesting one-dimensional and two-dimensional polymeric anions, respectively, are reported. The discussion of the novel and literature ionic structures includes a description of the molecular geometry of each of the components, the identification of packing trends, and an analysis of the hydrogen bonding and aromatic interactions occurring in the structures. The structures of all three families of organic components are compared, and trends in structural type, anion geometry, water inclusion, hydrogen bonding and functional group recognition are presented. In addition, a detailed analysis of robust crystal engineering synthons occurring in these structures is presented. Lastly the results of preliminary property investigations of the thermal and electronic properties of the materials are presented and discussed / Dissertation (MSc)--University of Pretoria, 2011. / Chemistry / unrestricted

Yes / Investigations of structural reactivity, molecular interactions and vibrational characterization of pharmaceutical drugs are helpful in understanding their behaviour. The aim of this study is to determine the molecular, electronic and chemical properties of the antibiotic drug nitrofurantoin (NF), after cocrystallisation with 3-aminobenzoic acid (3ABA) and to understand how those changes lead to variation of properties in the cocrystal NF–3ABA. NF–3ABA formation is explained by stabilization via the hydrogen-bond network between NF and 3ABA molecules. It is thoroughly characterized by IR, Raman and CP-MAS solid-state 13C NMR techniques, along with quantum chemical calculations. The results of IR, Raman, and 13C NMR analyses showed that imide N–H23 and C12[double bond, length as m-dash]O of NF interact with the acid C[double bond, length as m-dash]O and –OH groups in 3-ABA, respectively. Therefore the IR, Raman, and 13C NMR spectra verified the formation of N–H⋯O and O–H⋯O hydrogen bonds. To study hydrogen bonding interactions theoretically in NF–3ABA, two functionals B3LYP and wB97X-D have been used. A comparison is made between the results obtained by B3LYP and those predicted at the wB97X-D level. It is found that wB97X-D is best applied density functional theory (DFT) functional to describe the hydrogen bonding interactions. The strength and nature of hydrogen bonding in NF–3ABA have been analysed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. To validate the results obtained by QTAIM theory and to study the long-range forces, such as van der Waals interactions, the steric effects in NF–3ABA, the reduced density gradient (RDG) and the isosurface have been plotted using Multiwfn software. QTAIM and isosurface analysis suggested that the hydrogen bonding interactions present in NF–3ABA are moderate in nature. The calculated HOMO–LUMO energy gap shows that NF–3ABA is more active than NF and 3ABA. Chemical reactivity descriptors are calculated to understand the various aspects of pharmacological sciences. Chemical reactivity parameters show that NF–3ABA is softer and chemically more reactive than NF. The results suggest that cocrystals can be a feasible alternative for positively changing the targeted physicochemical properties of an active pharmaceutical ingredient (API). / V. R. Vangala acknowledges the financial support of the Royal Society of Chemistry for mobility grant (2015/17).

Le terme folate (vitamine B9) désigne une famille de molécules ayant une structure de base composée de 3 parties : un noyau pterine, un acide para-aminobenzoïque (pABA) et une chaine de glutamates. Le rôle de ces cofacteurs est de transporter des groupements monocarbonés. Ils interviennent dans de nombreuses réactions comme la synthèse des bases nucléiques, la synthèse de méthionine et la synthèse et le turnover de la S-adenosylmethionine,. Le folate est synthétisé chez les plantes et un grand nombre de micro-organismes dont les parasites du phylum des apicomplexes, tels que Plasmodium falciparum, et Toxoplasma gondii. Les enzymes impliquées dans cette voie de biosynthèse étant absentes chez l'homme, elles représentent des cibles herbicides, antibiotiques et antiparasitaires potentielles. Les inhibiteurs de la voie de biosynthèse du folate (tels que les sulfamides, analogues du pABA et inhibiteurs de la dihydroptéroate synthase, ou les inhibiteurs de la dihydrofolate réductase), sont souvent utilisés comme antibiotiques et antiparasitaires. Un problème majeur dans le traitement de ces maladies infectieuses est la résistance développée contre ces molécules, ce qui nécessite la recherche permanente de nouveaux médicaments. Le pABA est synthétisé en plusieurs étapes qui sont autant de cibles intéressantes pour développer de nouveaux inhibiteurs. Tout d'abord l'aminodeoxychorismate (ADC) synthase transforme le chorismate en ADC, puis dans une seconde étape, l'ADC est transformé en pABA par une ADC lyase. Chez les plantes supérieures et les parasites apicomplexes l'ADC synthase est une enzyme bifonctionnelle composée de deux grands domaines, un domaine glutamine amidotranferase (GAT) qui permet de produire le NH3 nécessaire à l'amination du chorismate, et un domaine ADC synthase (ADCS). Nous avons pu déterminer les paramètres cinétiques de la GAT-ADCS d'Arabidopsis. Nous avons constaté que ces deux domaines fonctionnent indépendamment, c'est-à-dire soit en présence de glutamine seule pour le domaine GAT (pas de chorismate), soit en présence de chorismate et de NH3 pour le domaine ADCS (pas de glutamine). Toutefois, le fonctionnement en tandem des deux domaines (tous les substrats sont présents) améliore les propriétés cinétiques (kcat) de chacun d'eux. Nos résultats montrent aussi que le NH3 produit par le domaine GAT et nécessaire à la synthèse de l'ADC n'est pas relargué dans le milieu extérieur mais canalisé (channeling) vers le domaine ADCS. Finalement, nous avons observé que l'ADC, produit final de la réaction, retro-inhibe le domaine ADCS en absence d'ADC lyase. Pris dans son ensemble, nos résultats indiquent que l'amination du chorismate est l'étape la plus limitante de la synthèse du pABA,.. Des expériences de criblage à haut débit nous ont permis d'identifier une molécule, la rubreserine, qui inhibe in vitro le domaine GAT de l'ADC synthase d'Arabidopsis avec un Ki autour de 8 µM. Nous avons observé que cette molécule inhibe la croissance de plantules d'Arabidopsis thaliana et la prolifération des parasites Toxoplasma gondii et Plasmodium falciparum avec des IC50 respectif de 65 µM, 20 µM et 1.2 µM. Chez Arabidopsis, la concentration en folate des cellules traitées est abaissée d'environ 40% par rapport au contrôle, une diminution qui n'a plus lieu en présence de pABA. L'ajout de pABA et de 5-formyltetrahydrofolate dans les milieux de culture d'Arabidopsis ou de Toxoplasma supprime en grande partie l'inhibition de croissance liée à la rubreserine, ce qui montre bien la connexion entre rubreserine et voie de biosynthèse du folate. Avec Toxoplama gondii, la rubreserine apparait plus efficace que les sulfamides pour bloquer l'invasion et la prolifération de ces parasites dans les fibroblastes humains. Ces résultats valident la GAT-ADCS comme cible anti-folate et montrent que la rubreserine a des propriétés anti-parasitaires intéressantes. / The term folate (vitamin B9) is a family of molecules with a basic structure composed of 3 parts: a core pterin, a para amino benzoic acid (PABA) moiety and a chain of glutamate. The role of these cofactors is to carry one-carbon groups. They are involved in many reactions such as the synthesis of nucleic acids, the synthesis of methionine and the synthesis and turnover of S-adenosylmethionine. Folate is synthesized in plants and many micro-organisms including parasites of the Apicomplexa phylum such as Plasmodium falciparum and Toxoplasma gondii. Several enzymes involved in the pathway are absent in humans, and so they are potential targets for herbicide, antibiotic and antiparasitic drugs. Inhibitors of folate biosynthesis (such as dihydropteroate synthase inhibitors, or inhibitors of dihydrofolate reductase), are often used as antibiotics and pesticides. A major problem in treating these infectious diseases is the resistance developed against these molecules, which requires a constant search for new drugs. pABA is synthesized in several steps which are all attractive targets for developing new inhibitors. First the aminodeoxychorismate (ADC) synthase converts chorismate into ADC, and then, in a second step, the ADC is converted to pABA by an ADC lyase. In higher plants and apicomplexan parasites the ADC synthase is a bifunctional enzyme composed of two main domains: a glutamine amidotranferase (GAT) domain that produces NH3, and an ADC synthase domain (ADCS) that catalyzes the amination of chorismate. We determined the kinetic parameters of the Arabidopsis GAT-ADCS. We found that these two domains function independently, that is to say either in the presence of glutamine alone for the GAT domain (no chorismate) or in the presence of chorismate and NH3 for the ADCS domain (no glutamine). However, the tandem operation of the two domains (all substrates are present) improves the kinetic properties (kcat) of each one. Our results also show that the NH3 produced by the GAT domain and required for the synthesis of ADC is not released into the surroundings but rather channeled to the active site of ADCS. Finally, we observed that ADC, the final product of the reaction, retro-inhibits the ADCS domain in the absence of ADC lyase. Taken together, our results indicate that the amination reaction of chorismate is the most limiting step of the synthesis of pABA. Using high-throughput screening approaches we have identified a molecule, rubreserine, which inhibits in vitro the GAT domain of Arabidopsis GAT-ADCS with a Ki value around 8 µM. We observed that this molecule inhibits the growth of Arabidopsis thaliana seedlings and the proliferation of Toxoplasma gondii and Plasmodium falciparum parasites with respective IC50 of 65 µM, 20 µM and 1 µM. In Arabidopsis, the concentration of folate in rubreserine-treated cells is lowered by about 40% compared to controls, a decrease that is suppressed in the presence of pABA. The addition of pABA and 5-Formyltetrahydrofolate in the culture media of Arabidopsis and Toxoplasma partly reverses the growth inhibition due to rubreserine, which shows the connection between the drug and folate biosynthesis. Rubreserine appears more effective than sulfa-drugs to block the invasion and proliferation of Toxoplasma gondii in human fibroblasts. These results validate the GAT-ADCS as an anti-folate target and show that rubreserine has interesting anti-parasitic properties.

A molécula de ácido orto-aminobenzóico tem sido intensamente empregada como sonda fluorescente no estudo de peptídeos e membranas e o entendimento dos efeitos de solvente sobre suas propriedades espectroscópicas apresenta grande interesse científico. Neste trabalho realizamos um estudo experimental e cálculos DFT sobre alterações nos espectros de absorção e emissão da sonda em solução aquosa, em função do pH do meio. Examinamos também o seu derivado 2-amino-N-metil benzamida (o-Abz-NHCH3) e as mudanças espectrais na interação com micelas de SDS. Resultados de experimentos de titulação mostraram-se coerentes com a existência de três estados de protonação para o-Abz à medida em que o pH torna-se ácido, resultantes da protonação dos grupos amino e carboxila, de modo semelhante ao que ocorre com aminoácidos. Para cada estado de protonação, realizamos cálculos de otimização de geometria e verificação de mínima energia com a teoria DFT utilizando diferentes funcionais e conjuntos de bases para orbitais atômicos. Partindo das geometrias de menor energia, com a teoria TD-DFT (B3LYP/311++G(d,p)) fizemos cálculos das transições eletrônicas. A melhor concordância com os resultados experimentais foi obtida com a molécula na forma aniônica. Na comparação dos resultados da posição espectral da transição de mais baixa energia, no processo de absorção ótica, observamos uma diferença relativa de 0,6%. Para a fluorescência otimizamos e verificamos a geometria do estado excitado e obtivemos as energias de transição vertical com o método TD-DFT (B3LYP/Def2-TZVP) com o qual tivemos um resultado de lambda = 407nm considerado satisfatório quando comparado com o valor experimental lambda= 394nm. Nas formas neutra e catiônica, as diferenças relativas entre os cálculos e os experimentos foram maiores, chegando a 11% na posição da banda de fluorescência da molécula neutra. Usando simulações de Dinâmica Molecular conseguimos estimar quantas moléculas de água se distribuem em torno do o-Abz. Os resultados mostram que, embora exista um número parecido de moléculas de água solvatando a molécula nas formas aniônica e catiônica, há uma redução na quantidade de ligações de hidrogênio realizadas pela protonação catiônica em relação à aniônica. O modelo utilizado para simular o o-Abz-NH(CH3) em micelas de SDS apresentou resultados satisfatórios com erro relativo entre 0,7\\% e 0,9%, no entanto são necessárias outras abordagens computacionais e experimentais para indicar em qual região a molécula se encontra na micela, dando assim mais confiabilidade e uma melhor interpretação aos resultados. / The ortho-aminobenzoic acid is a molecule largely employed as a fluorescent probe in peptide and membrane studies. The solvent dependence of its spectroscopic properties deserves great interest and we describe here results of experimental measurements and computational calculations by \\textit and Molecular Dynamics methods about spectroscopic and solvation properties of the molecule in aqueous medium at different pH values. We also examined the derivative 2-amino-N-methyl-benzamide (o-Abz-NHCH3), investigating the spectral modifications in its interaction with SDS micelles. The results of titration experiments could be interpreted as originated from three protonation states for o-Abz: in neutral pH and above, both carboxy and amine groups are deprotonated, and the molecule is in the anionic form. Decreasing the pH, protonation of amino group or carboxy renders the molecule neutral (pK = 5.0) and at low pH both groups are protonated and the molecule is in the cationic form (pK = 2.3). Geometry optimization and determination of energy minima were performed with the molecule in each protonation state using Density Functional Theory (DFT) with different functionals and basis set for atomic orbitals. Eletronic transitions were calculated from lowest energy geometry using TD-DFT (B3LYP/311++G(d,p)). The best agreement with experimental results were obtained for the anionic molecule: we observed a relative difference of 0.6\\% for the lowest energy optical transition. From the optimized geometry of the excited state the vertical transition was calculated with TD-DFT (B3LYP/Def2-TZVP), and the emission was predicted to occur at 407nm, a reasonable result compared with the experimental value or 394nm. For the molecule in neutral or cationic state, the relative differences between experimental and calculation results were greater, amounting to 11\\% for the fluorescence band in the neutral species. From Molecular Dynamics simulation we estimated the number of water molecules distributed aroud the o-Abz molecule. The results show that, although there is similar number of water molecules solvating the o-Abz in anionic and cationic state, there is a decrease in the amount of hydrogen bond in the cationic molecule. The simulation of the derivative o-Abz-NHCH3 in SDS micelles by implicit solvent methods gave results comparable to the experimental ones, with relative deviations lower than 1\\%. It should be noted that further study should be carried out in order to have a better knowledge about the location of the probe in the micelle, and to afford a beter interpretation of the results.

A molécula de ácido orto-aminobenzóico tem sido intensamente empregada como sonda fluorescente no estudo de peptídeos e membranas e o entendimento dos efeitos de solvente sobre suas propriedades espectroscópicas apresenta grande interesse científico. Neste trabalho realizamos um estudo experimental e cálculos DFT sobre alterações nos espectros de absorção e emissão da sonda em solução aquosa, em função do pH do meio. Examinamos também o seu derivado 2-amino-N-metil benzamida (o-Abz-NHCH3) e as mudanças espectrais na interação com micelas de SDS. Resultados de experimentos de titulação mostraram-se coerentes com a existência de três estados de protonação para o-Abz à medida em que o pH torna-se ácido, resultantes da protonação dos grupos amino e carboxila, de modo semelhante ao que ocorre com aminoácidos. Para cada estado de protonação, realizamos cálculos de otimização de geometria e verificação de mínima energia com a teoria DFT utilizando diferentes funcionais e conjuntos de bases para orbitais atômicos. Partindo das geometrias de menor energia, com a teoria TD-DFT (B3LYP/311++G(d,p)) fizemos cálculos das transições eletrônicas. A melhor concordância com os resultados experimentais foi obtida com a molécula na forma aniônica. Na comparação dos resultados da posição espectral da transição de mais baixa energia, no processo de absorção ótica, observamos uma diferença relativa de 0,6%. Para a fluorescência otimizamos e verificamos a geometria do estado excitado e obtivemos as energias de transição vertical com o método TD-DFT (B3LYP/Def2-TZVP) com o qual tivemos um resultado de lambda = 407nm considerado satisfatório quando comparado com o valor experimental lambda= 394nm. Nas formas neutra e catiônica, as diferenças relativas entre os cálculos e os experimentos foram maiores, chegando a 11% na posição da banda de fluorescência da molécula neutra. Usando simulações de Dinâmica Molecular conseguimos estimar quantas moléculas de água se distribuem em torno do o-Abz. Os resultados mostram que, embora exista um número parecido de moléculas de água solvatando a molécula nas formas aniônica e catiônica, há uma redução na quantidade de ligações de hidrogênio realizadas pela protonação catiônica em relação à aniônica. O modelo utilizado para simular o o-Abz-NH(CH3) em micelas de SDS apresentou resultados satisfatórios com erro relativo entre 0,7\\% e 0,9%, no entanto são necessárias outras abordagens computacionais e experimentais para indicar em qual região a molécula se encontra na micela, dando assim mais confiabilidade e uma melhor interpretação aos resultados. / The ortho-aminobenzoic acid is a molecule largely employed as a fluorescent probe in peptide and membrane studies. The solvent dependence of its spectroscopic properties deserves great interest and we describe here results of experimental measurements and computational calculations by \\textit and Molecular Dynamics methods about spectroscopic and solvation properties of the molecule in aqueous medium at different pH values. We also examined the derivative 2-amino-N-methyl-benzamide (o-Abz-NHCH3), investigating the spectral modifications in its interaction with SDS micelles. The results of titration experiments could be interpreted as originated from three protonation states for o-Abz: in neutral pH and above, both carboxy and amine groups are deprotonated, and the molecule is in the anionic form. Decreasing the pH, protonation of amino group or carboxy renders the molecule neutral (pK = 5.0) and at low pH both groups are protonated and the molecule is in the cationic form (pK = 2.3). Geometry optimization and determination of energy minima were performed with the molecule in each protonation state using Density Functional Theory (DFT) with different functionals and basis set for atomic orbitals. Eletronic transitions were calculated from lowest energy geometry using TD-DFT (B3LYP/311++G(d,p)). The best agreement with experimental results were obtained for the anionic molecule: we observed a relative difference of 0.6\\% for the lowest energy optical transition. From the optimized geometry of the excited state the vertical transition was calculated with TD-DFT (B3LYP/Def2-TZVP), and the emission was predicted to occur at 407nm, a reasonable result compared with the experimental value or 394nm. For the molecule in neutral or cationic state, the relative differences between experimental and calculation results were greater, amounting to 11\\% for the fluorescence band in the neutral species. From Molecular Dynamics simulation we estimated the number of water molecules distributed aroud the o-Abz molecule. The results show that, although there is similar number of water molecules solvating the o-Abz in anionic and cationic state, there is a decrease in the amount of hydrogen bond in the cationic molecule. The simulation of the derivative o-Abz-NHCH3 in SDS micelles by implicit solvent methods gave results comparable to the experimental ones, with relative deviations lower than 1\\%. It should be noted that further study should be carried out in order to have a better knowledge about the location of the probe in the micelle, and to afford a beter interpretation of the results.