Ce travail réalisé dans le cadre de l’initiative africaine de l’IUCr porte sur l’étude structurale par diffraction des rayons X de quelques architectures élaborées par association, via des interactions faibles, des anions {[M(C2O4)3]3-,M = Cr, Fe} et des cations complexes à base de la 2-picolylamine (amp) métaux de transition (Co2+, Cu2+ et Mn2+). L’architecture à base de l’ion Co2+ est bidimensionnelle et présente des feuillets ondulés constitués de chaines bimétalliques de chiralité différente où les deux ions complexes ([Cr(C2O4)3]3- et [Co(amp)3]3+ ) sont connectés par des liaisons hydrogène. Ces feuillets hébergent des molécules d’eau qui forment des clusters dodécamèriques aux caractéristiques nouvelles. Le composé déshydraté se réhydrate rapidement dans l’air ambiant et les deux états possèdent des couleurs différentes. Plusieurs cycles de déshydratation-réhydratation n’altèrent pas la qualité cristalline du composé. L’architecture à base des ions Cu2+ possède également des feuillets mais présente une ondulation plus forte que celle de l’architecture au cobalt. Ces couches sont constituées de chaines formées de cations dimériques [Cu2(amp)4Cl]3+ et d’anions {[M(C2O4)3]3-,M = Cr, Fe}. Les deux composés sont iso-structuraux et leur architecture présente des canaux monodimensionnels qui contiennent des molécules d’eau qui forment des clusters hexamèriques. Le composé subit des transitions de phase entre la basse température (100K) et la température de déshydratation (341K) avec une perte de la symétrie. Le composé se réhydrate plus difficilement que celui à base de l’ion cobalt(III). L’ion Mn2+ ne donne pas l’architecture escomptée mais un polymère de coordination nouveau / This work, realized under the IUCr initiative, framework involves the structural study via X-ray diffraction, of some heteromolecular architectures formed by the association through non-covalent bonds, between the tris (oxalato) chromate (III) and tris (oxalato) ferrate (III) anions {[M(C2O4)3]3-, M = Cr, Fe} and the cationic complex of the 2-picolylamine (amp) and transition metal (Co2 +, Cu2 + and Mn2 +). Co2 + ion builds two-dimensional corrugated layers made of bimetallic chiral chains where the two different complex ions ([Cr(C2O4)3]3- and [Co(amp)3]3 +) are connected by hydrogen bonds. These layers, connected by weak hydrogen interactions, host between them, water molecules which build dodecameric clusters having new characteristics. The dehydrated compound has different structure and color and is able to quickly reabsorb water molecules from surrounding to regenerate the initial compound despite that it has no pores. Several cycles of this process do not seriously affect the crystalline quality of this compound. The compound obtained with the Cu2 + ion also has a two-dimensional framework. Their layers are formed between the dimeric cation [Cu2 (amp) 4Cl]3 + and the anion {[M(C2O4)3]3-,M = Cr, Fe}. Both compounds are iso-structural; their frameworks are formed via π - - - π interactions and build 1D channels which contain water molecules forming hexameric clusters. The compound undergoes a phase transition between 100 K and the dehydration temperature (341K). During this dehydration, a loss of symmetry of the compound is recorded and rehydration process is more difficult than for cobalt(III)-framework. The use of Mn2+ ions does not give the expected architecture but a new coordination polymer

<p>This thesis presents novel approaches for structural investigation of glucuronides using chemical derivatization in combination with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MSⁿ).</p><p>Today, LC-ESI-MSⁿ is the dominant technique for quantitative as well as qualitative analyses of metabolites, due to its high sensitivity and selectivity. However, for compounds without an easily ionizable group, e.g., steroids, the sensitivity is limited. In the work presented in this thesis, a derivatization procedure forming a basic oxime significantly increased the detection sensitivity for the altrenogest glucuronide. </p><p>Furthermore, in structural evaluations of glucuronides, the limitation of LC-MSⁿ becomes evident due to the initial neutral loss of 176 u, i.e. monodehydrated glucuronic acid, which often makes it impossible to elucidate the structures of the conjugates. To solve this problem, the main part of the work described in this thesis was devoted to chemical derivatization as a means of facilitating the determination of the site of conjugation. </p><p>For the first time, the isomeric estriol glucuronides were evaluated using a combination of three reagents 2-chloro-1-methylpyridinium iodide (CMPI), 1-ethyl-3-(3-dimethyl- aminopropyl)-carbodiimide (EDC), and 2-picolylamine (PA). Interestingly, the derivatization gave a selective fragmentation pattern leading to differentiation of the isomers. </p><p>Another derivatization reagent, 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC), was also tested for the first time in structural investigations. The isomeric glucuronides of morphine, formoterol, and hydroxypropranolol were evaluated. They can all be conjugated in aliphatic as well as aromatic positions. DMISC was proven to be useful in two ways. Firstly, the morphine and formoterol glucuronides that contained a free phenol could be differentiated from those that were conjugated in the aromatic position based on different reactivity. Secondly, for the aromatic <i>O</i>-glucuronide of 4’-hydroxypropranolol, DMISC was proven to react with the amine. This product gave a different fragmentation pattern compared to the corresponding derivative of the aliphatic glucuronide. </p>

This thesis presents novel approaches for structural investigation of glucuronides using chemical derivatization in combination with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MSn). Today, LC-ESI-MSn is the dominant technique for quantitative as well as qualitative analyses of metabolites, due to its high sensitivity and selectivity. However, for compounds without an easily ionizable group, e.g., steroids, the sensitivity is limited. In the work presented in this thesis, a derivatization procedure forming a basic oxime significantly increased the detection sensitivity for the altrenogest glucuronide. Furthermore, in structural evaluations of glucuronides, the limitation of LC-MSn becomes evident due to the initial neutral loss of 176 u, i.e. monodehydrated glucuronic acid, which often makes it impossible to elucidate the structures of the conjugates. To solve this problem, the main part of the work described in this thesis was devoted to chemical derivatization as a means of facilitating the determination of the site of conjugation. For the first time, the isomeric estriol glucuronides were evaluated using a combination of three reagents 2-chloro-1-methylpyridinium iodide (CMPI), 1-ethyl-3-(3-dimethyl- aminopropyl)-carbodiimide (EDC), and 2-picolylamine (PA). Interestingly, the derivatization gave a selective fragmentation pattern leading to differentiation of the isomers. Another derivatization reagent, 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC), was also tested for the first time in structural investigations. The isomeric glucuronides of morphine, formoterol, and hydroxypropranolol were evaluated. They can all be conjugated in aliphatic as well as aromatic positions. DMISC was proven to be useful in two ways. Firstly, the morphine and formoterol glucuronides that contained a free phenol could be differentiated from those that were conjugated in the aromatic position based on different reactivity. Secondly, for the aromatic O-glucuronide of 4’-hydroxypropranolol, DMISC was proven to react with the amine. This product gave a different fragmentation pattern compared to the corresponding derivative of the aliphatic glucuronide.