A cationic copolymer as a cocatalyst for a peroxidase-mimicking heme-DNAzyme.

Heme binds to a parallel-stranded G-quadruplex DNA to form a peroxidase-mimicking heme-DNAzyme. An interpolyelectrolyte complex between the heme-DNAzyme and a cationic copolymer possessing protonated amino groups was characterized and the peroxidase activity of the complex was evaluated to elucidate the effect of the polymer on the catalytic activity of the heme-DNAzyme. We found that the catalytic activity of the heme-DNAzyme is enhanced through the formation of the interpolyelectrolyte complex due to the general acid catalysis of protonated amino groups of the polymer, enhancing the formation of the iron(IV)oxo porphyrin π-cation radical intermediate known as Compound I. This finding indicates that the polymer with protonated amino groups can act as a cocatalyst for the heme-DNAzyme in the oxidation catalysis. We also found that the enhancement of the activity of the heme-DNAzyme by the polymer depends on the local heme environment such as the negative charge density in the proximity of the heme and substrate accessibility to the heme. These findings provide novel insights as to molecular design of the heme-DNAzyme for enhancing its catalytic activity.

Three-dimensional finite element analysis of extra short implants focusing on implant designs and materials.

AIM: When using short implants, fracture of the implant body and bone resorption are a concern because stress concentrates on and around a short implant. The purpose of this research is to investigate the differences in stress distribution between tissue level (TL) and bone level (BL) implant body designs, and between commercially pure titanium (cpTi) and the newer titanium-zirconium (TiZr) alloy in using short implants. MATERIALS AND METHODS: Models of TL and BL implants were prepared for three-dimensional finite element analysis. The implants were produced in 10 mm, 8 mm, and 6 mm lengths, and the TL was also produced in a 4-mm length. A static load of 100 N inclined at 30° to the long axis was applied to the buccal side of the model. The largest maximum principal stress value in the cortical bone and the largest von Mises stress value in the implant body were evaluated. RESULTS: Stress concentration was observed at the connection part of the implant, especially above the bone in TL and within the bone in BL. In the TL design, tensile stress occurred on the buccal side and compressive stress on the lingual side of the cortical bone. Conversely, in the BL design, tensile stress occurred on the lingual side of the cortical bone. CpTi and TiZr showed a similar stress distribution pattern. The maximum stress values were lower in the TL design than the BL design, and they were lower with TiZr than cpTi for both the cortical bone and implant body. The maximum value tended to increase as the length of the implant body decreased. In addition, the implant body design was more influential than its length, with the TL design showing a stress value similar to the longer BL design. CONCLUSION: Using TiZr and a TL design may be more useful mechanically than cpTi and a BL design when the length of the implant body must be shorter because of insufficient vertical bone mass in the mandible.

Structures and Catalytic Activities of Complexes between Heme and All Parallel-Stranded Monomeric G-Quadruplex DNAs.

Heme in its ferrous and ferric states [heme(Fe2+) and heme(Fe3+), respectively] binds selectively to the 3'-terminal G-quartet of all parallel-stranded monomeric G-quadruplex DNAs formed from inosine(I)-containing sequences, i.e., d(TAGGGTGGGTTGGGTGIG) DNA(18mer) and d(TAGGGTGGGTTGGGTGIGA) DNA(18mer/A), through a π-π stacking interaction between the porphyrin moiety of the heme and the G-quartet, to form 1:1 complexes [heme-DNA(18mer) and heme-DNA(18mer/A) complexes, respectively]. These complexes exhibited enhanced peroxidase activities, compared with that of heme(Fe3+) alone, and the activity of the heme(Fe3+)-DNA(18mer/A) complex was greater than that of the heme(Fe3+)-DNA(18mer) one, indicating that the 3'-terminal A of the DNA sequence acts as an acid-base catalyst that promotes the catalytic reaction. In the complexes, a water molecule (H2O) at the interface between the heme and G-quartet is coordinated to the heme Fe atom as an axial ligand and possibly acts as an electron-donating ligand that promotes heterolytic peroxide bond cleavage of hydrogen peroxide bound to the heme Fe atom, trans to the H2O, for the generation of an active species. The intermolecular nuclear Overhauser effects observed among heme, DNA, and Fe-bound H2O indicated that the H2O rotates about the H2O-Fe coordination bond with respect to both the heme and DNA in the complex. Thus, the H2O in the complex is unique in terms of not only its electronic properties but also its dynamic ones. These findings provide novel insights into the design of heme-deoxyribozymes and -ribozymes.

Characterization of Catalytic Activities and Heme Coordination Structures of Heme-DNA Complexes Composed of Some Chemically Modified Hemes and an All Parallel-Stranded Tetrameric G-Quadruplex DNA Formed from d(TTAGGG).

Heme binds selectively to the 3'-terminal G-quartet (G6 G-quartet) of an all parallel-stranded tetrameric G-quadruplex DNA, [d(TTAGGG)]4, to form a heme-DNA complex. Complexes between [d(TTAGGG)]4 and a series of chemically modified hemes possessing a heme Fe atom with a variety of electron densities were characterized in terms of their peroxidase activities to evaluate the effect of a change in the electron density of the heme Fe atom (ρFe) on their activities. The peroxidase activity of a complex decreased with a decreasing ρFe, supporting the idea that the activity of the complex is elicited through a reaction mechanism similar to that of a peroxidase. In the ferrous heme-DNA complex, carbon monoxide (CO) can bind to the heme Fe atom on the side of the heme opposite the G6 G-quartet, and a water molecule (H2O) is coordinated to the Fe atom as another axial ligand, trans to the CO. The stretching frequencies of Fe-bound CO (νCO) and the Fe-C bond (νFe-C) of CO adducts of the heme-DNA complexes were determined to investigate the structural and electronic natures of the axial ligands coordinated to the heme Fe atom. Comparison of the νCO and νFe-C values of the heme-DNA complexes with those of myoglobin (Mb) revealed that the donor strength of the axial ligation trans to the CO in a complex is considerably weaker than that of the proximal histidine in Mb, as expected from the coordination of H2O trans to the CO in the complex.

Outstanding compressive creep strength in Cr/Ir-codoped (Mo0.85Nb0.15)Si2 crystals with the unique cross-lamellar microstructure.

A (Mo0.85Nb0.15)Si2 crystal with an oriented, lamellar, C40/C11b two-phase microstructure is a promising ultrahigh-temperature (UHT) structural material, but its low room-temperature fracture toughness and low high-temperature strength prevent its practical application. As a possibility to overcome these problems, we first found a development of unique "cross-lamellar microstructure", by the cooping of Cr and Ir. The cross-lamellar microstructure consists of a rod-like C11b-phase grains that extend along a direction perpendicular to the lamellar interface in addition to the C40/C11b fine lamellae. In this study, the effectiveness of the cross-lamellar microstructure for improving the high-temperature creep deformation property, being the most essential for UHT materials, was examined by using the oriented crystals. The creep rate significantly reduced along a loading orientation parallel to the lamellar interface. Furthermore, the degradation in creep strength for other loading orientation that is not parallel to the lamellar interface, which has been a serious problem up to now, was also suppressed. The results demonstrated that the simultaneous improvement of high-temperature creep strength and room temperature fracture toughness can be first accomplished by the development of unique cross-lamellar microstructure, which opens a potential avenue for the development of novel UHT materials as alternatives to existing Ni-based superalloys.