Cytochrome P450 27A1 (P450 27A1 or CYP27A1) is an important enzyme that participates in different pathways of cholesterol degradation as well as in the activation of vitamin D(3). Several approaches were utilized to investigate how two physiological substrates, cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol, interact with CYP27A1. The enzyme active site was first probed spectrally by assessing binding of the two substrates and five substrate analogues followed by computer modeling and site-directed mutagenesis. The computer models suggest that the spatial positions and orientations of cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol are different in the enzyme active site. As a result, some of the active site residues interact with both substrates, although they are situated differently relative to each steroid, and some residues bind only one substrate. Mutation of the overlapping substrate-contact residues (W100, H103, T110, M301C, V367, I481, and V482) affected CYP27A1 binding and enzyme activity in a substrate-dependent manner and allowed identification of several important side chains. T110 is proposed to interact with the 12alpha-hydroxyl of 5beta-cholestane-3alpha,7alpha,12alpha-triol, whereas V367 seems to be crucial for correct positioning of the cholesterol C26 methyl group and for regioselective hydroxylation of this substrate. Distinct binding of the CYP27A1 substrates may provide insight into why phenotypic manifestations of cerebrotendinous xanthomatosis, a disease associated with CYP27A1 deficiency, are so diverse.
This review article critically discusses examples of asymmetric synthesis of tailor-made α-amino acids via homologation of Ni(II) complexes of glycine and alanine Schiff bases, reported in the literature from 2013 through the end of 2016. Where it is possible, reaction mechanism and origin of the stereochemical outcome is discussed in detail. Special attention is given to various aspects of practicality and scalability of the reported methods. Among the most noticeable developments in this area are novel designs of axially chiral ligands, application of electro- and mechano-chemical (ball-milling) conditions, and development of dynamic kinetic resolution procedures.
Summary As part of our investigations of a new chemical imbibition idea (using surfactant or brine formulations) to stimulate oil recovery from shale, we are studying oil flow through and, especially, brine intake into shale to displace oil. Our first studies in this area focused on an outcrop shale, specifically the Odanah member of Pierre shale in North Dakota, USA. We studied porosity, permeability to oil, permeability to water, and spontaneous brine intake for the Pierre shale. We found that porosities for Pierre shale cores were relatively high—from 25 to 35%. Porosities for our measurements of Bakken cores averaged less than 3%. Bakken oil imbibed into dry Pierre shale cores (up to 5 mm in thickness) to the same extent as could be achieved by forced injection of oil (i.e., achieving the same oil saturations for both processes). Permeability to a clean mineral oil (Soltrol 130™) was higher than for Bakken oil—apparently because of deposition of wax/asphaltenes/particulates on the Pierre core faces when injecting Bakken oil. Permeability to oil for Pierre shale cores (with no water present) ranged from 3.32×10–5 to 2.19×10–4 md when injecting Bakken oil and from 4.85×10–4 to 2.34×10–3 md when injecting Soltrol 130. Permeability to Bakken oil for a Bakken core (with no water present) averaged 4.84×10–4 md. In Pierre shale and Bakken cores with thicknesses ranging from 0.65 to 5 mm, permeabilities were basically independent of flow rate, in agreement with expectations from the Darcy equation. Saline brine spontaneously entered into oil-saturated Pierre cores, yielding recovery values up to 41% of original oil in place (OOIP). During exposure to brine, our results indicated an increase in permeability—presumably by mineral dissolution during forced brine injection and by cracking (possibly caused by clay swelling) during spontaneous brine intake. This result is encouraging for the application of imbibition to enhance oil recovery from shale. Before these studies, we feared that exposure to brine might reduce shale permeability because of clay swelling. The laboratory results will help during a current study of surfactant and brine imbibition in the Bakken formation.
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