The Pore Network and the Adsorption Characteristics of Mesoporous Silica Aerogel: Adsorption Kinetics on a Timescale of Seconds

Mesoporous silica aerogel particles of ca. 5 μm in diameter can be conveniently produced by grinding in an aqueous phosphate buffer at pH 7. The pores in the suspended aerogel particles are spherical and their diameter is 18–20 nm, as measured by NMR cryoporometry. NMR diffusiometry revealed that diffusion of water is hindered inside the pores of the aerogel. In spite of steric hindrance, bulk water and pore water exchange rapidly on the millisecond timescale in the suspension, indicating a highly interconnected pore network. The adsorption of methylene blue (MB), as a model compound, was studied on the silica aerogel particles. The process was followed by on-line UV-Vis spectrophotometry after injecting the dye into the aerogel suspension. Biphasic kinetics were observed with the first process complete in ca. 80 s and the second in ca. 600 s. A detailed kinetic model was developed for the interpretation of the results. It postulates a relatively fast adsorption process with Langmuir-type kinetics, and the aggregation of aerogel particles covered by the dye on a longer timescale. The aggregates are involved in a reversible sedimentation process which actually removes MB from the suspension

The pore network and the adsorption characteristics of mesoporous silica aerogel: adsorption kinetics on a timescale of seconds

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Mechanism of drug release from silica-gelatin aerogel-relationship between matrix structure and release kinetics

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On the rich chemistry of pseudo‐protic ionic liquid electrolytes

Mixing weak acids and bases can produce highly complicated binary mixtures, called pseudo-protic ionic liquids, in which a complex network of effects determines the physicochemical properties that are currently impossible to predict. In this joint computational-experimental study, we investigated 1-methylimidazole-acetic acid mixtures through the whole concentration range. Effects of the varying ionization and excess of either components on the properties, such as density, diffusion coefficients, and overall hydrogen bonding structure were uncovered. A special emphasis was put on understanding the multiple factors that govern the conductivity of the system. In the presence of an excess of acetic acid, the 1-methylimidazolium acetate ion pairs dissociate more efficiently, resulting in a higher concentration of independently moving, conducting ions. However, the conductivity measurements showed that higher concentrations of acetic acid improve the conductivity beyond this effect, suggesting in addition to standard dilution effects the occurrence of Grotthuss diffusion in high acid-to-base ratios. The results here will potentially help designing novel electrolytes and proton conducting systems, which can be exploited in a variety of applications

Gelatin content governs hydration induced structural changes in silica-gelatin hybrid aerogels – Implications in drug delivery

Silica-gelatin hybrid aerogels of varying gelatin content (from 4 wt.% to 24 wt.%) can be conveniently impregnated with hydrophobic active agents (e.g. ibuprofen, ketoprofen) in supercritical CO2 and used as drug delivery systems. Contrast variation neutron scattering (SANS) experiments show the molecular level hybridization of the silica and the gelatin components of the aerogel carriers. The active agents are amorphous, and homogeneously dispersed in these porous, hybrid matrices. Importantly, both fast and retarded drug release can be achieved with silica-gelatin hybrid aerogels, and the kinetics of drug release is governed by the gelatin content of the carrier. In this paper, for the first time, a molecular level explanation is given for the strong correlation between the composition and the functionality of a family of aerogel based drug delivery systems. Characterization of the wet aerogels by SANS and by NMR diffusiometry, cryoporometry and relaxometry revealed that the different hydration mechanisms of the aerogels are responsible for the broad spectrum of release kinetics. Low-gelatin (4–11 wt.%) aerogels retain their open-porous structure in water, thus rapid matrix erosion dictates fast drug release from these carriers. In contrast to this, wet aerogels of high gelatin content (18–24 wt.%) show well pronounced hydrogel-like characteristics, and a wide gradual transition zone forms in the solid-liquid interface. The extensive swelling of the high-gelatin hybrid backbone results in the collapse of the open porous structure, that limits mass transport towards the release medium, resulting in slower, diffusion controlled drug release

Behavior of PAMAM dendrimers in aqueous solution and their interaction with small molecules

A doktori munkám során célul tűztük ki az 5. generációs NH2-végcsoportú PAMAM dendrimer (G5.NH2) oldatbeli viselkedésének, oldószerrel (H2O), kisméretű ionokkal (H3O+, AuIII, PO43-), molekulákkal (doxorubicin) és kolloidokkal (különböző méretű arany nanorészecskék, AuNP) valamint a dendrimer funkcionalizált változatának doxorubicinnal való kölcsönhatásának vizsgálatát. Munkánk során a makromolekulák protonálódási folyamatait és a foszfátionokkal való kölcsönhatást pH-potenciometriás titrálással vizsgáltuk, míg a dendrimerek oldatbeli szerkezetének vizsgálatára és az ionokkal, kismolekulákkal, kolloidokkal való kölcsönhatások jellemzésére különböző 1D és 2D NMR technikákat (1H, 13C, 15N NMR spektrumok és COSY, NOESY, HSQC, HMBC, DOSY) alkalmaztunk. Azonosítottuk a G5.NH2 dendrimer különböző kémiai környezetben lévő protonjait az 1H NMR spektrumon, és megállapítottuk, hogy az az irodalomban számos esetben helytelenül szerepel. A dendrimer struktúrában feltételezett üregek létezését NMR krioporozimetriás mérésekkel vizsgálva megállapítottuk, hogy 1000 vízmolekula/dendrimer aránynál 1,8 és ~2,6 nm sugarú pórusok találhatóak a dendrimergélben, a víz arányát növelve (2000 és 3000 vízmolekula/dendrimer), csak a nagyobb pórusok vannak jelen, míg a 4000 vízmolekula/dendrimer arány esetén már nem definiálható jól a pórusos szerkezet. A méretviszonyok alapján megállapítottuk, hogy egy-egy üreget legalább két dendrimer együttesen hoz létre. A G5.NH2 dendrimer potenciometriás titrálása során kapott titrálási görbe illesztésével két csoportállandót tudtunk meghatározni, melyből az egyik a tercier (pKN(T) = 5,7(2)), a másik a primer nitrogének (pKN(P) = 8,9(2)) protonálódásához rendelhető, míg a különböző pH-értékű dendrimer-oldatok 1H NMR spektrumain a tercier illetve a primer N-ekhez (N(T) és N(P)) közeli protonok csúcsainak kémiai eltolódását vizsgálva bizonyítottuk a pK-értékek hovatartozását. NMR és pH-potenciometriás kísérletekkel igazoltuk, hogy a foszfátionok a protonált primer aminocsoportokkal vannak elektrosztatikus kölcsönhatásban, míg pH = 6-8 között a dendrimer szerkezetének elágazási pontjaiban lévő tercier nitrogénatomokhoz feltehetően hidrogénkötéssel kötődnek, a pH-val és foszfátkoncentrációval változó mértékben, változtatva ezáltal a makromolekula méretét, struktúráját, töltését. A dendrimer templátú arany nanorészecskék képződése során eredményeink alapján N(P)+ – AuIII ionpár alakul ki, így a szintézis első lépését alkotó AuIII – dendrimer kölcsönhatásban komplexképződés nem történik. A kemoterapeutikumként számon tartott doxorubicin a diffúziometriás eredményeink alapján képes adduktumot képezni a különböző módon funkcionalizált PAMAM dendrimerekkel (G5.Ac, G5.SAH, G5.GlyOH), erősebb kölcsönhatást a G5.Ac és a G5.SAH dendrimerekkel tapasztaltunk. Az átlagos diffúzió együttható értékekből kiszámoltuk az arany nanorészecskét (AuNP) tartalmazó dendrimerek („hibrid nanorészecskék”) méretét: a részecskék 7-9 nm-es átmérője olyan struktúra kialakulásával magyarázható, melyben 3-4 dendrimer molekula fogja közre az arany nanorészecskéket, így ezek átmenetet képeznek a kapszulázott és sztérikusan stabilizált AuNP-k között.The aim of our work was to study the characters of fifth generation PAMAM dendrimers with -NH2 terminal groups (G5.NH2) in solution and their interaction with the solvent (H2O), small ions (H3O+, AuIII, PO43-), molecules (doxorubicin) and colloids (gold nanoparticles, AuNP, of different size) in detail. In our work, the protonation processes of the macromolecules and the interaction with phosphate ions were investigated with pH potentiometric titration, while different 1D and 2D NMR methods (1H, 13C, 15N NMR and COSY, NOESY, HSQC, HMBC, DOSY) were used to characterize the structure of the dendrimer in aqueous solution and to get more insight into the interactions. We performed the 1H NMR assignment of the protons being in the same chemical environment of the G5.NH2, and determined that there are mistakes in the assignment in the literature. We investigated the supposed cavities in the structure of the dendrimers using NMR cryoporometry, and observed that at 1000 water/dendrimer ratio pores in the gel show 1.8 and ~2.6 nm radii, at 2000 and 3000 water/dendrimer ratio only the larger pores appeared, while at the largest (4000 H2O/G5.NH2) water content mainly the bulk water could have been detected. From the determined pore size and the size of the dendrimer molecule we determined that one cavity is defined by at least two dendrimers. With pH potentiometric titration we could determine the group constant of the G5.NH2 dendrimer for the primary (pKN(P) = 8,9(2)) and tertiary amines (pKN(T) = 5,7(2)) as well, being in accordance with the NMR titration experiments (pKN(T) = 5,76 and 5,96; pKN(P) = 8,7). A wide range of NMR and pH potentiometric experiments proved that phosphate ions are in electrostatic interaction with the protonated primary amines, while from about pH 6 to 7.5 they are inside the dendrimer, bind to the tertiary amines in the branching points supposedly by H-bonds and changes the size, structure and charge of the macromolecule. On the basis of the higher shielding we concluded ion pair formation between the protonated primary amines and AuIII-ions, thus we found no complex formation before the formation of dendrimer templated gold nanoparticles. Doxorubicin, a widely used chemotherapeutic agent, is able to form adduct with functionalized G5 PAMAM dendrimers (G5.Ac, G5.SAH, G5.GlyOH) according to our diffusion NMR results, but under the conventional reaction conditions a relatively small amount of DOX can be encapsulated by the macromolecules. From the average diffusion coefficients of the bound dendrimers interacting with AuNPs, we determined the size of the hybrid nanoparticles at different G5.NH2/AuNP ratio: the diameter of 7-9 nm can be explained with a model of 3-4 dendrimer molecules surrounding and stabilizing the AuNP, thus the measured hybrid nanoparticles form a transition state between the encapsulated (DEN) and sterically stabilized (DSN) gold nanoparticles