Synthesis of silica aerogel films in liquid molds.

By virtue of their low density and thermal conductivity, aerogels constitute attractive thermal insulators. Of those, aerogel films are best suited for thermal insulation in microsystems. Processes for the synthesis of aerogel films with thicknesses smaller than 2 µm or thicker than 1 mm are well established. However, for microsystems films in the range of a few microns and up to several hundred microns would be beneficial. To circumvent the present limitations, we describe a liquid mold made of two immiscible liquids, used here to produce aerogel films thicker than 2 µm in a single molding step. Following gelation and aging, the gels were removed from the liquids and dried using supercritical carbon dioxide. In contrast to spin/dip coating, liquid molding avoids solvent evaporation from the gel's outer surface during gelation and aging, films are free-standing and have smooth surfaces. The choice of liquids determines the aerogel film thickness. As a proof of concept, 130 µm thick homogeneous and high porosity (>90%) silica aerogel films were synthesized in a liquid mold with fluorine oil and octanol. The resemblance of the liquid mold approach to the float glass technique offers the prospect of mass production of large sheets of aerogel films.

Structuring light using solgel hybrid 3D-printed optics prepared by two-photon polymerization.

Three-dimensional direct laser writing based on a two-photon polymerization process of hybrid organic-inorganic material was used to print micrometer-scale refractive phase elements that were designed to manipulate incoming Gaussian beams into line and square intensity-flattened profiles. Here we present new results of shaping light beams, enabled by tailoring a two-photon absorption process for printing hybrid material structures based on a fast solgel process. The optical design and calculations of the optical elements are described, along with characterization of their performance in manipulating incoming light beams. The novelty described in this work, to the best of our knowledge, is the implementation of 3D solgel materials as better and improved micro-optics. This new ability provides upgraded 3D high resolution and smooth, printed optical phase structures using tailored hybrids with improved optical and mechanical properties compared to standard common photoresists. This opens new and exciting opportunities for compact and robust beam shaping by reaching glassy material properties and overcoming limitations of organic polymers.

Gradual hydrophobization of silica aerogel for controlled drug release.

We report on the successful fine-tuning of silica aerogel hydrophobicity, through a gas-phase surface modification process. Aerogel hydrophobicity is a widely discussed matter, as it contributes to the aerogel's preservation and determines its functionality. Still, a general procedure for tuning the hydrophobicity, without affecting other aerogel properties was missing. In the developed procedure, silica aerogel was modified with trimethylchlorosilane vapor for varying durations, resulting in gradual hydrophobicity, determined by solid-state NMR and contact angle measurements. The generality of this post-synthesis treatment allows its application on a variety of aerogel materials, while having minimum effect on their porosity and transparency. We demonstrate the applicability of the gradual hydrophobization by tuning drug release rates from the silica aerogel. Two chlorhexidine salts - widely employed as antiseptic agents - were used as model drugs, one representing a soluble drug, and the other an insoluble drug; they were entrapped in silica aerogel, following hydrophobization to varying degrees. The drug release patterns showed that depending on the degree, hydrophobization can increase or decrease release kinetics, compared to the unmodified aerogel. This arises from the effect of the hydrophobic degree on pore structure, diffusional rates and wetting of the aerogel carrier. We suggest the use of the gradual hydrophobization process for other drug-aerogel systems, as well as for other aerogel applications, such as transparent insulation panels, contaminate sorbents or catalysis supports.

Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant.

Gemcitabine 5'-diphosphate (F(2)CDP) is a potent inhibitor of ribonucleotide reductases (RNRs), enzymes that convert nucleotides (NDPs) to deoxynucleotides and are essential for DNA replication and repair. The Escherichia coli RNR, an alpha2beta2 complex, when incubated with 1 equiv of F(2)CDP catalyzes the release of two fluorides and cytosine concomitant with enzyme inactivation. In the presence of reductant (thioredoxin/thioredoxin reductase/NADPH or DTT), the enzyme inactivation results from its covalent labeling of alpha with the sugar of F(2)CDP (one label/alpha2beta2). SDS-PAGE analysis of the inactivated RNR without boiling of the sample reveals that alpha migrates as an 87 and 110 kDa protein in a ratio of 0.6:0.4. When the reductant is omitted, RNR is inactivated by loss of the essential tyrosyl radical and formation of a new radical. Inactivation studies with C225S-alpha in the presence or absence of reductants, reveal it behaves like wt-RNR in the absence of reductant. Inactivated C225S-alpha migrates as an 87 kDa protein and is not covalently modified. C225 is one of the cysteines in RNR's active site that supplies reducing equivalents to make dNDPs. To identify the new radical formed, [1'-(2)H]-F(2)CDP was studied with wt- and C225S-RNR by 9 and 140 GHz EPR spectroscopy. These studies revealed that the new radical is a nucleotide derived with g values of g(x) 2.00738, g(y) 2.00592, and g(z) 2.00230 and with altered hyperfine interactions (apparent triplet collapsed to a doublet) relative to [1'-(1)H]-F(2)CDP. The EPR features are very similar to those we recently reported for the nucleotide radical generated with CDP and E441Q-RNR.

Structure of the nitrogen-centered radical formed during inactivation of E. coli ribonucleotide reductase by 2'-azido-2'-deoxyuridine-5'-diphosphate: trapping of the 3'-ketonucleotide.

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides providing the monomeric precursors required for DNA replication and repair. The class I RNRs are composed of two homodimeric subunits: R1 and R2. R1 has the active site where nucleotide reduction occurs, and R2 contains the diiron tyrosyl radical (Y*) cofactor essential for radical initiation on R1. Mechanism-based inhibitors, such as 2'-azido-2'-deoxyuridine-5'-diphosphate (N(3)UDP), have provided much insight into the reduction mechanism. N(3)UDP is a stoichiometric inactivator that, upon interaction with RNR, results in loss of the Y* in R2 and formation of a nitrogen-centered radical (N*) covalently attached to C225 (R-S-N*-X) in the active site of R1. N(2) is lost prior to N* formation, and after its formation, stoichiometric amounts of 2-methylene-3-furanone, pyrophosphate, and uracil are also generated. On the basis of the hyperfine interactions associated with N*, it was proposed that N* is also covalently attached to the nucleotide through either the oxygen of the 3'-OH (R-S-N*-O-R') or the 3'-C (R-S-N*-C-OH). To distinguish between the proposed structures, the inactivation was carried out with 3'-[(17)O]-N(3)UDP and N* was examined by 9 and 140 GHz EPR spectroscopy. Broadening of the N* signal was detected and the spectrum simulated to obtain the [(17)O] hyperfine tensor. DFT calculations were employed to determine which structures are in best agreement with the simulated hyperfine tensor and our previous ESEEM data. The results are most consistent with the R-S-N*-C-OH structure and provide evidence for the trapping of a 3'-ketonucleotide in the reduction process.