Elucidating the Electronic Nature of Rh-based Paddlewheel Catalysts from 103 Rh NMR Chemical Shifts: Insights from Quantum Mechanical Calculations.

The tremendous importance of dirhodium paddlewheel complexes for asymmetric catalysis is largely the result of an empirical optimization of the chiral ligand sphere about the bimetallic core. It was only recently that a H(C)Rh triple resonance 103 Rh NMR experiment provided the long-awaited opportunity to examine - with previously inconceivable accuracy - how variation of the ligands impacts on the electronic structure of such catalysts. The recorded effects are dramatic: formal replacement of only one out of eight O-atoms surrounding the metal centers in a dirhodium tetracarboxylate by an N-atom results in a shielding of the corresponding Rh-site of no less than 1000 ppm. The current paper provides the theoretical framework that allows this and related experimental observations made with a set of 19 representative rhodium complexes to be interpreted. In line with symmetry considerations, it is shown that the shielding tensor responds only to the donor ability of the equatorial ligands along the perpendicular principal axis. Axial ligands, in contrast, have no direct effect on shielding but may come into play via the electronic c i s ${cis}$ -effect that they exert onto the neighboring equatorial sites. On top of these fundamental interactions, charge redistribution within the core as well as the electronic t r a n s ${trans}$ -effect of ligands of different donor strengths is reflected in the recorded 103 Rh NMR shifts.

Catalytic Asymmetric Fluorination of Copper Carbene Complexes: Preparative Advances and a Mechanistic Rationale.

The Cu-catalyzed reaction of substituted α-diazoesters with fluoride gives α-fluoroesters with ee values of up to 95 %, provided that chiral indane-derived bis(oxazoline) ligands are used that carry bulky benzyl substituents at the bridge and moderately bulky isopropyl groups on their core. The apparently homogeneous solution of CsF in C6 F6 /hexafluoroisopropanol (HFIP) is the best reaction medium, but CsF in the biphasic mixture CH2 Cl2 /HFIP also provides good results. DFT studies suggest that fluoride initially attacks the Cu- rather than the C-atom of the transient donor/acceptor carbene intermediate. This unusual step is followed by 1,2-fluoride shift; for this migratory insertion to occur, the carbene must rotate about the Cu-C bond to ensure orbital overlap. The directionality of this rotatory movement within the C2 -symmetric binding site determines the sense of induction. This model is in excellent accord with the absolute configuration of the resulting product as determined by X-ray diffraction using single crystals of this a priori wax-like material grown by capillary crystallization.

Supramolecular architecture of theophylline polymorphs, monohydrate and co-crystals with iodine: study from the energetic viewpoint.

The regularities of crystal structure organization were thoroughly studied in all to date known polymorphic modifications of theophylline (THP) using an energetic approach. The monohydrate and a co-crystal of theophylline with one half equivalent of an iodine molecule were similarly investigated. The calculations of pairwise interaction energies have showed that the crystals studied can be divided into two groups according to their basic structural motifs: columnar-layered or columnar. The energetic approach also allows the role of different interactions in the crystal structure formation to be estimated. It was found that strong N-H⋯N, N-H⋯O hydrogen bonds and stacking interactions play the most important roles in polymorphic modifications of THP and the THP monohydrate. In the case of the co-crystal with iodine, N-H⋯O hydrogen bond participates in the dimeric building unit formation. However, instead of a stacking interaction the π⋯π interaction between carbonyl groups of neighboring molecules plays the highest role in the supramolecular architecture of this crystal. The lattice energies calculations in periodic conditions for polymorphic structures have shown that polymorph with the most anisotropic energetic structure may be considered as stable and all others forms metastable. In the polymorphic modification 1 of THP a zwitter-ionic resonance form is predominant, which affects significantly the solubility and the intermolecular interactions of this modification.

BTZ-Derived Benzisothiazolinones with In Vitro Activity against Mycobacterium tuberculosis.

8-Nitro-1,3-benzothiazin-4-ones (BTZs) are known as potent antitubercular agents. BTZ043 as one of the most advanced compounds has reached clinical trials. The putative oxidation products of BTZ043, namely, the corresponding BTZ sulfoxide and sulfone, were reported in this journal (Tiwari et al. ACS Med. Chem Lett. 2015, 6, 128-133). The molecular structures were later revised to the constitutionally isomeric benzisothiazolone and its 1-oxide, respectively. Here, we report two BTZ043-derived benzisothiazolinones (BITs) with in vitro activity against mycobacteria. The constitutionally isomeric O-acyl benzisothiazol-3-ols, in contrast, show little or no antimycobacterial activity in vitro. The structures of the four compounds were investigated by X-ray crystallography and NMR spectroscopy. Molecular covalent docking of the new compounds to Mycobacerium tuberculosis decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1) suggests that the active BITs exert antimycobacterial activity through inhibition of DprE1 like BTZs.

iChoose Kidney: A Clinical Decision Aid for Kidney Transplantation Versus Dialysis Treatment.

BACKGROUND: Despite a significant survival advantage of kidney transplantation compared with dialysis, nearly one third of end-stage renal disease (ESRD) patients are not educated about kidney transplantation as a treatment option at the time of ESRD diagnosis. Access to individualized, evidence-based prognostic information is needed to facilitate and encourage shared decision making about the clinical implications of whether to pursue transplantation or long-term dialysis. METHODS: We used a national cohort of incident ESRD patients in the US Renal Data System surveillance registry from 2005 to 2011 to develop and validate prediction models for risk of 1- and 3-year mortality among dialysis versus kidney transplantation. Using these data, we developed a mobile clinical decision aid that provides estimates of risks of death and survival on dialysis compared with kidney transplantation patients. RESULTS: Factors included in the mortality risk prediction models for dialysis and transplantation included age, race/ethnicity, dialysis vintage, and comorbidities, including diabetes, hypertension, cardiovascular disease, and low albumin. Among the validation cohorts, the discriminatory ability of the model for 3-year mortality was moderate (c statistic, 0.7047; 95% confidence interval, 0.7029-0.7065 for dialysis and 0.7015; 95% confidence interval, 0.6875-0.7155 for transplant). We used these risk prediction models to develop an electronic, user-friendly, mobile (iPad, iPhone, and website) clinical decision aid called iChoose Kidney. CONCLUSIONS: The use of a mobile clinical decision aid comparing individualized mortality risk estimates for dialysis versus transplantation could enhance communication between ESRD patients and their clinicians when making decisions about treatment options.