Our goal was to study the effect of heat treatment temperature and heating rate on the microstructure and crystalline phases and assess the domain of existence of sub-micrometer fluorapatite crystals in niobium-doped fluorapatite glass-ceramics for biomedical applications. Glass-ceramic specimens were prepared by casting and heat treatment between 700 and 1200°C using a fast or a slow heating rate. The microstructure was characterized by atomic force microscopy and scanning electron microscopy. Crystalline phases were analyzed by x-ray diffraction. AFM of the as-cast glass revealed that amorphous phase separation occurred in this system. XRD confirmed the presence of fluorapatite in all specimens, together with forsterite and enstatite at higher temperatures. Both heating rate and heat treatment temperature strongly influenced microstructure and crystallinity. A dual microstructure with sub-micrometer fluorapatite crystals and polygonal forsterite crystals was obtained when slow heating rates and crystallization temperatures between 950 and 1100°C were used. Needle-shaped fluorapatite crystals appeared after heat treatment above 1100°C. Fast heating rates led to an increase in crystal size. Heat treatment temperatures should remain below 1100°C, together with slow heating rates, to prevent crystal dissolution, and preserve a dual microstructure of finely dispersed sub-micrometer crystals without growth of needle-shaped crystals.

A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]-pyrimidine with 1,3-bis(benzyloxy)-2-propoxymethyl chloride afforded compound 3, which without isolation was debrominated to obtain 4-amino-5-cyano-7-[[1,3-bis(benzyloxy)-2- propoxy]methyl]pyrrolo[2,3-d]pyrimidine. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 4 were successfully cleaved by boron trichloride to afford 4-amino-5-cyano-7-[(1,3-dihydroxy-2- propoxy)methyl]pyrrolo[2,3-d]pyrimidine. Conventional functional group transformation of the cyano group of 6 provided a number of novel 5-substituted derivatives. Tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were treated separately with sodium metaperiodate and then with sodium borohydride to afford the 2',3'-seco derivatives 9a-c, respectively. The acyclic nucleoside 4-chloro-2-(methylthio)-7-[[1,3-bis(benzyloxy)-2- propoxy]methyl]pyrrolo[2,3-d]pyrimidine was aminated, desulfurized with Raney Ni, and then debenzylated to provide the tubercidin analogue 11. Cytotoxicity evaluation against L1210 murine leukemic cells in vitro showed that although the parent compounds tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were very potent growth inhibitors, the acyclic derivatives 6, 7a-c, and 9a-c had only slight growth-inhibitory activity. Evaluation of compounds 6, 7a, 7b, 7c, 9a, 9b, 9c, 11 for cytoxicity and activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the carboxamide (7a) and the thioamide (7c) were active. Compound 7c was the more potent of the two, inhibiting HCMV but not HSV-1 at concentrations producing little cytotoxicity.

A number of 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine derivatives related to the nucleoside antibiotics toyocamycin and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine (1) with (2-acetoxyethoxy)methyl bromide (2) afforded a mixture of 4-amino-6-bromo-5-cyano-7-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d] pyrimidine (3) and the corresponding N1 isomer. Debromination of this mixture gave the corresponding 4-amino-5-cyano-7-[(2-acetoxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidi ne (4) and 4-amino-5-cyano-1-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d]pyrimidin e (5). Deacetylation of 4 and 5 furnished 4-amino-5-cyano-7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine (6) and the corresponding N1 isomer (7), respectively. The sites of attachment for the acyclic moiety for 6 and 7 were assigned on the basis of UV spectral studies as well as 13C NMR spectroscopy. Conventional functional group transformation of 6 provided a number of novel 5-substituted derivatives (8-10), including the sangivamycin derivative 8. The methyl formimidate derivative 10 was converted to the thioamide derivative 11 and the carbohydrazide derivative 12. Compounds 6 and 8-12 were tested for cytotoxicity to L1210 murine leukemic cells in vitro. None of these compounds caused significant inhibition of cell growth. Evaluation of compounds 4 and 6-12 for activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the thioamide (11) was active. It inhibited HCMV but not HSV-1 at concentrations producing only slight cytotoxicity in human foreskin fibroblasts (HFF cells) and KB cells.

The purpose of this study was primarily to determine the feasibility of heat-pressing a mica-based glass-ceramic with the use of commercially available dental equipment, and secondly to evaluate the effect of various processing variables on the degree of crystal alignment in the pressed glass-ceramic. The hypotheses were that the mica-based glass-ceramic could be successfully heat-pressed and that some degree of crystal orientation would be obtained, depending on the processing variables. The glass composition was melted at 1400 degrees C for 2 h and cast into 12 x 60-mm rods. Ingots (10 x 12 mm) were cut from the glass rods, heat treated, and heat-pressed under various conditions. The microstructure of the pressed specimens was investigated by SEM and compared to that of heat-treated controls. The length of Vickers-induced cracks was measured on heat-pressed specimens and heat-treated controls. The results showed that mica-based glass-ceramics could be successfully pressed with the use of commercially available dental equipment. The resulting degree of crystal alignment (texture) along the direction of pressing varied between 35 +/- 6 and 79 +/- 6. There was a linear relationship between the degree of texture and the apparent aspect ratio of the mica platelets. A significant decrease in the length of the Vickers-induced cracks in the direction perpendicular to pressing was observed, associated with an increase in length in the direction of pressing.

No abstract