Crystal engineering of co-crystals and host-guest systems for environmentally friendly applications: sunscreens stabilization, pollutant sequestering and herbicide reformulation.

Solid state engineered materials have proven to be useful and suitable tools in the quest of new materials. In this thesis different crystalline compounds were synthesized to provide more sustainable products for different applications, as in cosmetics or in agrochemistry, to propose pollutants removal strategy or to obtain materials for electrocatalysis. Therefore, the research projects presented here can be divided into three main topics: (i) sustainable preparation of solid materials of widely used active ingredients aimed at the reduction of their occurrence in the natural environment. The systems studied in this section are cyclodextrins host-guest compounds, obtained via mechanochemical and slurry synthesis. The first chemicals studied are sunscreens inclusion complexes, that proved to have enhanced photostability and desired photoprotection. The same synthetic methods were applied to obtain inclusion complexes of bentazon, a herbicide often found to leach in groundwaters. The resulting products showed to have desired water solubility properties. The same herbicide was also adsorbed on amorphous calcium phosphate nanoparticles, to obtain a biocompatible formulation of this agrochemical. This herbicide could benefit by the adsorption on nanoparticles for what concerns its kinetic release in different media as well as its photostability. (ii) Sustainable synthesis of co-crystals based on polycyclic aromatic hydrocarbons, for the proposal of a sequestering method with a resulting material with enhanced properties. The co-crystallization via mechanochemical means proved that these pollutants can be sequestered via simple solvent-free synthesis and the obtained materials present better photochemical properties when compared to the starting co-formers. (iii) Crystallization from mild solvents of nanosized materials useful for the application in electrocatalysis. The study of compounds based on nickel and cobalt metal ions resulted in the obtainment of 2D and 1D coordination polymers. Moreover, solid solutions were obtained. These crystals showed layered structures and, according to preliminary results, they can be exfoliated.

Host-guest interactions between xanthones and water: the role of O-H center dot center dot center dot O, C-H center dot center dot center dot O, and pi center dot center dot center dot pi contacts in the channel- and cage-type frameworks

In this article were studied two xanthone derivatives known as 1,5-dihydroxy-8-methoxyxanthone (I) and 1,3,7-trihydroxy-8-methoxyxanthone (II), which show one water molecule into their crystal structures. In xanthone I, there are water wires contributing to build up channel-like cavities along the c axis, whereas in xanthone II the water is surrounded by three xanthone molecules forming a cage-type structure. The geometries of I and II were optimized using the density functional theory method with B3LYP functional, and the results were compared with crystal structure. Both theoretical and experimental investigations reveal a concordance between structural parameters, with the xanthone core presenting an almost flat conformation and substituents adopting the more stable orientations. In the two compounds, the hydroxyl group linked at position 1 is involved in a resonance-assisted hydrogen bond with the carbonyl group. Besides, the supramolecular arrangement of the host/guest systems are stabilized mainly by classical intermolecular hydrogen bonds (O-H center dot center dot center dot O) involving xanthone-to-water and xanthone-to-xanthone. In addition, C-H center dot center dot center dot O weak hydrogen bonds, as well as pi-pi interactions play an important role to stabilize the crystal self-assembly of xanthones I and II. The results reported here underline the role of inclusion of water molecules and their different arrangement into the crystal structure of two xanthone host/guest systems.

Kinetics of photoinduced birefringence in the guest-host system of poly(methyl methacrylate) doped with azobenzene-containing crown ethers

The kinetics of the buildup and decay of photoinduced birefringence was examined in a series of host-guest systems: azobenzene-containing crown ethers, differing in the size of the crowns, dissolved in a poly (methyl methacrylate) matrix. In all samples, the kinetics of the buildup of the birefringence was reasonably described by a sum of two exponential functions, the time constants being inversely proportional to the intensity of the pumping light and the magnitudes of the signals at the saturation level depending on the pumping light intensity and sample thickness. The dark decays were best described by the stretched exponential function, with the characteristic parameters (time constant and stretch coefficient) being practically independent of the type of crown ether. The time constants of the signal decay were orders of magnitude shorter than the respective constants of the dark isomerization of the azo crown ethers, thus indicating that the process controlling the decay was a relaxation of the polymer matrix and/or a rearrangement of the flexible parts of the crowns. (C) 2007 Wiley Periodicals, Inc.

Host-guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), Hydroxypropyl-beta-cyclodextrin (HP-beta-CD), Dimethyl-beta-cyclodextrin (DM-beta-CD) and gamma-cyclodextrin (gamma-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand-Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-beta-CD > beta-CD > alpha-CD > HP-beta-CD > gamma-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.

Host-Guest interaction between herbicide oxadiargyl and hydroxypropyl-β-cyclodextrin

In the face of a growing human population and increased urbanization, the demand for pesticides will simply rise. Farmers must escalate yields on increasingly fewer farm acres. However, the risks of pesticides, whether real or perceived, may force changes in the way these chemicals are used. Scientists are working toward pest control plans that are environmentally sound, effective, and profitable. In this context the development of new pesticide formulations which may improve application effectiveness, safety, handling, and storage can be pointed out as a solution. As a contribution to the area, the microencapsulation of the herbicide oxadiargyl (OXA) in (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) was performed. The study was conducted in different aqueous media (ultrapure water and in different pH buffer solutions). In all cases an increment of the oxadiargyl solubility as a function of the HP-β-CD concentration that has been related to the formation of an inclusion complex was verified. UV-Vis and NMR experiments allowed concluding that the stoichiometry of the OXA/HP-β-CD complex formed is 1 : 1. The gathered results can be regarded as an important step for its removal from industrial effluents and/or to increase the stabilizing action, encapsulation, and adsorption in water treatment plants.

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV-Vis, (1)H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a B(S)-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 +/- A 837 M(-1). Stoichiometry was established by the UV spectrophotometer using Job`s plot method and, also confirmed by molecular modeling. Data from (1)H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-beta-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Host-guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cyclodextrin Inclusion Complexes Loaded in Particles as Drug Carrier Systems

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hydrodynamic Characterization of Bile Salt Host-Guest Complexes by Pulsed Field Gradient NMR Spectroscopy

The work described herein is aimed at understanding primary and secondary aggregation of bile salt micelles and how micelles can perform chiral recognition of binapthyl analytes. Previous work with cholate and deoxycholate using micellar electrokinetic chromatography (MEKC) and nuclear magnetic resonance (NMR) has provided insightinto cholate and deoxycholate micelle formation, especially with respect to the critical micelle concentration (CMC). Chiral separations of the model analyte, 1,1â??-binaphthyl-2,2â??-diyl hydrogen phosphate (BNDHP), via cholate (C) and deoxycholate (DC) mediated MEKC separataions previously have shown the DC CMC to be 7-10 mM andthe cholate CMC at 14 mM at ph 12. A second model analyte,1,1â??-binaphthol (BN), was also previously investigated to probe micellar structure, but the MEKC data for this analyte implied a higher CMC, which may be interpreted as secondary aggregation. Thiswork extends the investigation of bile salts to include pulsed field gradient spin echo (PFGSE) NMR experiments being used to gain information about the size and degree of polydispersity of cholate and deoxycholate micelles. Concentrations of cholate below 10mM show a large variation in effective radius likely due to the existence of transient preliminary aggregates. The onset of the primary micelle shows a dramatic increase in effective radius of the micelle in cholate and deoxycholate. In the region of expectedsecondary aggregation a gradual increase of effective radius was observed with cholate; deoxycholate showed a persistent aggregate size in the secondary micelle region that is modulated by the presence of an analyte molecule. Effective radii of cholate anddeoxycholate (individually) were compared with and without R- and S-BNDHP in order to observe the effective radius difference of micelles with and without analyte present. The presence of S-BNDHP consistently resulted in a larger effective aggregate radius incholate and deoxycholate, confirming previous data of the S-BNDHP interacting more with the micelle than R-BNDHP. In total, various NMR techniques, like diffusion NMR can be used to gain a greater understanding of the bile salt micellization process and chiral resolution.