Polymorph selection by continuous crystallization

This article is motivated by a remarkable observation reported recently by Myerson, Trout, and co‐workers that continuous crystallization is capable of producing metastable polymorphs in stable steady‐state operation. We explain why this phenomenon occurs and give simple design rules for reproducing it in other polymorphic systems. A linear stability analysis gives simple functions of parameters for which one can continuously produce thermodynamically metastable products based only on the relative polymorph dynamics. We demonstrate agreement with two sets of experimental data; L‐glutamic acid grown from aqueous solution and p‐aminobenzoic acid also grown from aqueous solution. For many polymorphic compounds, engineering a process to produce a desired polymorph is as simple as finding a reasonable operating point for the continuous mixed‐suspension mixed‐product removal crystallization process (temperature, residence time, initial supersaturation, etc.) according to the rules reported in this article. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3505–3514, 2016     

Experimental evaluation of the water ingression mechanism for corium cooling

Experiments were performed to assess the significance of water ingression cooling in the quenching of molten corium. Water ingression is a mechanism by which water penetrates into cracks and pores of solidified corium to enhance cooling that would otherwise be severely limited by the low thermal conductivity of the material. Quench tests were conducted with 2100 °C melts weighing 75 kg composed of UO₂, ZrO₂ and chemical constituents of concrete. The amount of concrete in the melts was varied between 4% and 23%. The melts were quenched with an overlying water layer; three tests were conducted at a system pressure of 1 bar and four tests at 4 bar. The measured cooling rates were found to decrease with increasing concrete content and, contrary to expectations, are essentially independent of system pressure. For the lower concrete content melts, cooling rates exceeded the conduction-limited rate with the difference being attributed to the water ingression mechanism. Measurements of the permeability of the corium “ingots” produced by the quench tests were used to obtain a second, independent set of dryout heat flux data, which exhibits the same trend as the quench test data. The data was used to validate an existing dryout heat flux model based on corium permeability associated with thermally induced cracking. The model uses the thermal and mechanical properties of the corium and coolant, and it reproduces the very particular data trend found for the dryout heat flux as a function of concrete content. The model predicts that water ingression cooling would be most effective for concrete-free corium mixtures such as in-vessel type melts. For such a melt the model predicts a dryout heat flux of 400 kW/m² at a pressure of 1 bar. The results of this study provide an experimental basis for a water ingression model that can be incorporated into computer codes used to assess accident management strategies.     

Historical trends in the lead isotopic composition of archival Sphagnum mosses from Scotland (1838-2000)

The analysis of almost 200 Scottish Sphagnum moss samples collected over the past 170 years has revealed trends in the isotopic composition of lead similar to those previously established for dated Scottish lake sediments and peat bogs, lending credibility to these proxy records of atmospheric lead contamination and deposition. The effect of temporal variations in contributions from sources such as smelting of indigenous lead ores (206Pb/207Pb approximately 1.16-1.18), coal combustion (206Pb/207Pb approximately 1.17-1.19), and the use of imported Australian lead (206Pb/207Pb approximately 1.04) was clearly seen in the Scottish moss 206Pb/207Pb record. This showed some differences from the corresponding archival herbage record for the south of England, where the initial influence of Australian lead occurred earlier, at the end of the 19th century. A significant decline from a 206Pb/ 207Pb value of approximately 1.17 in the Scottish moss record began in the 1920s and continued until the 1980s (206Pb/207Pb approximately 1.12). The success of measures to reduce lead emissions to the atmosphere over the past 20 years in the U.K., in particular from petrol-engined vehicles using alkyl lead additives manufactured primarily from Australian lead, is evident in both the increasing 206Pb/207Pb ratio and falling lead concentration data for Scottish moss.     

ATP/GTP hydrolysis is required for oxazole and thiazole biosynthesis in the peptide antibiotic microcin B17

In the maturation of the Escherichia coli antibiotic Microcin B17, the product of the mcbA gene is modified posttranslationally by the multimeric Microcin synthetase complex (composed of McbB, C, and D) to cyclize four Cys and four Ser residues to four thiazoles and four oxazoles, respectively. The purified synthetase shows an absolute requirement for ATP or GTP in peptide substrate heterocyclization, with GTP one-third as effective as ATP in initial rate studies. The ATPase/GTPase activity of the synthetase complex is conditional in that ADP or GDP formation requires the presence of substrate; noncyclizable versions of McbA bind to synthetase, but do not induce the NTPase activity. The stoichiometry of ATP hydrolysis and heterocycle formation is 5:1 for a substrate that contains two potential sites of modification. However, at high substrate concentrations (>50Km) heterocycle formation is inhibited, while ATPase activity occurs undiminished, consistent with uncoupling of NTP hydrolysis and heterocycle formation at high substrate concentrations. Sequence homology reveals that the McbD subunit has motifs reminiscent of the Walker B box in ATP utilizing enzymes and of motifs found in small G protein GTPases. Mutagenesis of three aspartates to alanine in these motifs (D132, D147, and D199) reduced Microcin B17 production in vivo and heterocycle formation in vitro, suggesting that the 45 kDa McbD has a regulated ATPase/GTPase domain in its N-terminal region necessary for peptide heterocyclization.     

The association of complete laryngotracheoesophageal cleft with left lung agenesis: pathophysiological clues provided by an experiment of nature

The authors present a patient with complete laryngotracheoesophageal cleft and concurrent left lung agenesis and microgastria. Prenatal ultrasound scan showed polyhydramnios and a hypertrophic right lung. The authors propose that the combination of right lung hypertrophy, polyhydramnios, and microgastria in the absence of a competent laryngeal mechanism may suggest that the preferential path for swallowed amniotic fluid was into the lung, rather than the normal route through the stomach. This case illustrates the prenatal findings suggestive of complete laryngotracheoesophageal cleft and lung agenesis, and suggests a potential causal relationship between shunting of swallowed amniotic fluid into the bronchial tree and prenatal lung hypertrophy and microgastria.     

Stereochemical course of enzymatic enolpyruvyl transfer and catalytic conformation of the active site revealed by the crystal structure of the fluorinated analogue of the reaction tetrahedral intermediate bound to the active site of the C115A mutant of MurA

MurA (UDP-GlcNAc enolpyruvyl transferase), the first enzyme in bacterial peptidoglycan biosynthesis, catalyzes the enolpyruvyl transfer from phosphoenolpyruvate (PEP) to the 3'-OH of UDP-GlcNAc by an addition-elimination mechanism that proceeds through a tetrahedral ketal intermediate. The crystal structure of the Cys115-to-Ala (C115A) mutant of Escherichia coli MurA complexed with a fluoro analogue of the tetrahedral intermediate revealed the absolute configuration of the adduct and the stereochemical course of the reaction. The fluorinated adduct was generated in a preincubation of wild-type MurA with (Z)-3-fluorophosphoenolpyruvate (FPEP) and UDP-GlcNAc and purified after enzyme denaturation. The fluorine substituent stabilizes the tetrahedral intermediate toward decomposition by a factor of 10(4)-10(6), facilitating manipulation of the adduct. The C115A mutant of MurA was utilized to avoid the microheterogeneity that arises in the wild-type MurA from the attack of Cys115 on C-2 of FPEP in competition with the formation of the fluorinated adduct. The crystal structure of the complex was determined to 2.8 A resolution, and the absolute configuration at C-2 of the adduct was found to be 2R. Thus, addition of the 3'-OH of UDP-GlcNAc is to the 2-si face of FPEP, corresponding to the 2-re face of PEP. Given the previous observation that, in D2O, the addition of D+ to C-3 of PEP proceeds from the 2-si face [Kim, D. H., Lees, W. J., and Walsh, C. T. (1995) J. Am. Chem. Soc. 117, 6380-6381], the addition across the double bond of PEP is anti. Also, because the overall stereochemical course has been shown to be either anti/syn or syn/anti [Lees, W. J., and Walsh, C. T. (1995) J. Am. Chem. Soc. 117, 7329-7337], it now follows that the stereochemistry of elimination of H+ from C-3 and Pi from C-2 of the tetrahedral intermediate of the reaction is syn.