Molecular Cage Assembly by Sn−O−Sn Bridging of Di-, Tri- and Tetranuclear Organotin Tectons: Extending the Spacing in Double Ladder Structures

Hydrolysis reactions of di- and trinuclear organotin halides yielded large novel cage compounds containing Sn−O−Sn bridges. The molecular structures of two octanuclear tetraorganodistannoxanes showing double-ladder motifs, viz., [{Me₃SiCH₂(Cl)SnCH₂YCH₂Sn(OH)CH₂SiMe₃}₂(μ-O)₂]₂ [ 1 , Y=p-(Me)₂SiC₆H₄-C₆H₄Si(Me)₂] and [{Me₃SiCH₂(I)SnCH₂YCH₂Sn(OH)CH₂SiMe₃}₂(μ-O)₂]₂ ⋅ 0.48 I₂ [ 2⋅ 0.48 I₂, Y=p-(Me)₂SiC₆H₄-C₆H₄Si(Me)₂], and the hexanuclear cage-compound 1,3,6-C₆H₃(p-C₆H₄Si(Me)₂CH₂Sn(R)₂OSn(R)₂CH₂Si(Me)₂C₆H₄-p)₃C₆H₃-1,3,6 ( 3 , R=CH₂SiMe₃) are reported. Of these, the co-crystal 2⋅ 0.48 I₂ exhibits the largest spacing of 16.7 Å reported to date for distannoxane-based double ladders. DFT calculations for the hexanuclear cage and a related octanuclear congener accompany the experimental work.     

Methods for the calculation of spherically averaged Compton profiles with GTOs

For the first time, an analytical and efficient algorithm for the evaluation of spherically averaged reciprocal form factors B(s)=〈B( s )〉_Ω using Gauss-type basis functions is presented. The spherically averaged Compton profile is available by Fourier transformation of the reciprocal form factor. The algorithm has been successfully implemented in connection with the quantum chemistry codes GAMESS and CRYSTAL92, which perform Hartree–Fock calculations for molecules and solids. In addition, an analytical algorithm for the direct evaluation of spherically averaged Compton profiles and the moments 〈p^ν〉 (ν≥−1) via the momentum density is proposed for Gauss-type basis functions. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 65 : 213–223, 1997     

Neutral loss of amino acid residues from protonated peptides in collision-induced dissociation generates N- or C-terminal sequence ladders

The widespread occurrence of the neutral loss of one to six amino acid residues as neutral fragments from doubly protonated tryptic peptides is documented for 23 peptides with individual sequences. Neutral loss of amino acids from the N-terminus of doubly charged tryptic peptides results in doubly charged y-ions, forming a ladder-like series with the ions [M + 2H](2+) = y(max) (2+), y(max - 1) (2+), y(max - 2) (2+), etc. An internal residue such as histidine, proline, lysine or arginine appears to favor this type of fragmentation, although it was sometimes also observed for peptides without this structure. For doubly protonated non-tryptic peptides with one of these residues at or near the N-terminus, we observed neutral loss from the C-terminus, resulting in a doubly charged b-type ion ladder. The analyses were performed by Q-TOF tandem mass spectrometry, facilitating the recognition of neutral loss ladders by their 2+ charge state and the conversion of the observed mass differences into reliable sequence information. It is shown that the neutral loss of amino acid residues requires low collision offset values, a simple mechanistic explanation based on established fragmentation rules is proposed and the utility of this neutral loss fragmentation pathway as an additional source for dependable peptide sequence information is documented.     

Enantioselective synthesis of 5-methylidenedihydrouracils as potential anticancer agents

An efficient, versatile, enantioselective synthesis of 1,3-disubstituted and 1,3,6-trisubstituted 5-methylidenedihydrouracils applying Horner-Wadsworth Emmons methodology was developed. Starting 1,3-disubstituted 5-diethoxyphosphoryluracils were subjected to reduction of the double bond or addition of various Grignard reagents and obtained Horner-Wadsworth Emmons reagents were used for the olefination of formaldehyde. Enantioselective synthesis of 1,3,6-trisubstituted 5-methylidenedihydrouracils was accomplished by introducing (R,R)- or (S,S)-di(1-phenylethylamino)phosphoryl groups as chiral auxiliary. Additions of Grignard reagents in the presence of these groups were highly and complimentary diastereoselective (de?～?80%). Further separation of the diastereomeric mixtures by column chromatography enabled synthesis of (R)- and (S)-1,3,6-trisubstituted-5-methylidenedihydrouracils with ee?≥?98%. Furthermore, absolute configuration of the adducts and final products was established using single crystal X-ray analysis. Stereochemical course of the addition reactions is also discussed.     

Analysis of carbenoxolone by ultra‐high‐performance liquid chromatography tandem mass spectrometry in mouse brain and blood after systemic administration

Carbenoxolone is a derivative of glycyrrhetinic acid found in the root of Glycyrrhiza glabra, colloquially known as licorice. It has been used as a treatment for peptic and oral ulcers. In recent years, carbenoxolone has been utilized in basic research for its ability to block gap junctional communication. Better understanding the distribution of carbenoxolone after systemic administration can lead to a better understanding of its potential sites of action. Presented is an ultra high‐performance liquid chromatography tandem mass spectrometer (UHPLC–MS/MS) method for the identification and quantification of carbenoxolone in mouse blood and brain tissue. Twenty mice were injected intraperitoneally with 25 mg/kg carbenoxolone and brain tissue and blood were collected for analysis. Blood concentrations (mean ± SD) at 15, 30, 60 and 120 min were determined to be (n = 5) 5394 ± 778, 2636 ± 836, 1564 ± 541 and 846 ± 252 ng/mL, respectively. Brain concentrations (mean ± SD) at 15, 30, 60 and 120 mins were determined to be (n = 5) 171 ± 62, 102 ± 35, 55 ± 10 and 27 ± 9 ng/g, respectively. The analysis of these specimens at the four different time points resulted in blood and brain half‐lives in mice of ~43 and 41 min, respectively. The UHPLC–MS/MS method was determined to be sensitive and robust for quantification of carbenoxolone.     

The synthesis of cyclic polymers by olefin metathesis: Achievements and challenges

Cyclic polymers have drawn considerable interest for their peculiar physical properties in comparison to linear polymers, despite their equivalent compositions. Synthetically, cyclic polymers can be accessed through either macrocyclic ring‐closure or by ring‐expansion polymerization, but the main challenge with either method is the production of highly pure cyclic polymer samples. This highlight describes advances in the area of cyclic polymer synthesis, with a particular focus on ring‐expansion metathesis polymerization. Methods for characterizing cyclic polymers and assessing their purity are also discussed in order to emphasize the need for additional robust and reliable methods for synthesizing and studying topologically complex macromolecules. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 228–242     

Determination of niacin in infant formula by solid-phase extraction/liquid chromatography: peer-verified method performance-interlaboratory validation

This paper reports the results of the interlaboratory peer validation study of AOAC Peer-Verified Method (PVM) 1:2,000 for the determination of niacin in infant formula by solid-phase extraction/liquid chromatography. We have used a Data Quality Objectives (DQO) approach to address not only method variability and robustness but also accuracy of data through the use of an appropriate reference material in conjunction with the interlaboratory validation study. Our DQO included the following: (1) statistical agreement of analytical results and quantitative recovery between 2 collaborating laboratories; (2) the repeatability relative standard deviation (RSDr) values and the HORRAT (Horwitz ratio) obtained (1.07), which satisfied the criteria of the Horwitz "limits of acceptability" at the analyte level present; (3) validation of lack of interference; and (4) accuracy agreement within assigned values for a certified reference material. National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1846 Infant Formula, with a certified value of 63.3 +/- 7.6 microg/g for niacin content, was used as a test material for collaborative study and accuracy assessment. Niacin values obtained by the originating laboratory were 59.7 +/- 4.0 microg/g (95% confidence interval [CI] = 1.4 microg/g with a relative standard deviation [RSD] of 6.7%) and by the peer laboratory were 56.6 +/- 6.6 microg/g (95% CI = 4.1 microg/g, with an RSD of 11.7%). Statistical evaluation using the means equivalence test showed that nicotinic acid values obtained by the peer laboratory were equivalent to those values obtained by the originating laboratory. Linear calibration curves and quantitative recovery were obtained. Integration of the PVM process with a readily available certified reference material gives the user confidence in the accuracy of the data generated by the method through traceability to the reference material used.     

Synthesen im system {carbonylmetallat/ketenimin/säure}: XXX. Neue ferra- und rhenaazetidine

The metal carbonyl anions [Fe(η-C₅H₅(CO)₂]^? and [Re(CO)₅] undergo regio- and site-specific [2 + 2]-cycloadditions with the ketenimines Ph₂CCNR (R = Me, Ph) to give the (isolable) anionic complexes [L_n$\text{M{C(CPh}{}_2\text{)N(R)C}$(O)}]^? (L_nM = Fe(η-C₅H₅)CO, Re(CO)₄) which have been alkylated and acylated at the exocyclic oxygen atom of the carbonyl function. The result is stable neutral complexes having a metallaazetidine structure which is composed of an α-metallated enamine and an N,O carbene part. IR, ¹H, and ¹³C NMR data are presented.     

Neues über Oxouranate: Über α-Li6UO6. Mit einer Bemerkung über β-Li6UO6

New Investigations about Oxo Uranates: On α-Li₆UO₆. With a Remark about β-Li₆UO₆ The crystal structure of transparent, bright yellow single crystals of α-Li₆UO₆ has been determined. [a = 838.07(5), c = 738.34(7) pm; d_pyk = 4.02, d_x = 4.17 g · cm^?3; space group R3 ; Z = 3; R = 3.17%, R_w = 3.06%; 408 symmetry independent I₀(hkl); AgKα fourcircle diffractometer Philips PW 1100]. The structure is dominated by a threedimensional framwork of “hollow spaces”, built up by 12 O^2? (and 12 Li⁺). The Madelung Part of Lattice Energy, MAPLE, is calculated and discussed.