An ‘inside-out’ approach to suramin analogues

An approach to the synthesis of suramin analogues has been realised, which avoids synthetic problems associated with conventional routes. The use of isobutyl ester protecting groups for sulfonic acids was crucial to the success of the strategy, because these were able to be cleanly deprotected with sodium iodide, yielding the sodium salts of the corresponding sulfonic acids.     

Fluorine teams up with water to restore inhibitor activity to mutant BPTI

Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C–F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine β-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in “chemical complementation” that has a significantly favorable impact on protein–protein interactions.     

Reply to ‘comment on “extending Hirshfeld‐I to bulk and periodic materials”’

The issues raised in the comment by Manz are addressed through the presentation of calculated atomic charges for NaF, NaCl, MgO, SrTiO $$_3$$ , and La $$_2$$ Ce $$_2$$ O $$_7$$ , using our previously presented method for calculating Hirshfeld‐I charges in solids (Vanpoucke et al., J. Comput. Chem. doi: 10.1002/jcc.23088). It is shown that the use of pseudovalence charges is sufficient to retrieve the full all‐electron Hirshfeld‐I charges to good accuracy. Furthermore, we present timing results of different systems, containing up to over 200 atoms, underlining the relatively low cost for large systems. A number of theoretical issues are formulated, pointing out mainly that care must be taken when deriving new atoms in molecules methods based on “expectations” for atomic charges. © 2012 Wiley Periodicals, Inc.     

A protocol to accomplish ‘homo-Robinson’ annulation: application to the guanacastepene problem

A sequence which accomplishes the preparation of cycloheptadienones by ring-expansion of fused cyclohexenones has been developed and applied to the improved synthesis of a key intermediate in the total synthesis of guanacastepene A.     

Conversion of endohedral <Superscript>133</Superscript>Xe-fullerene to endohedral <Superscript>133</Superscript>Xe-fullerenol to be used in nuclear medicine

Summary Hydrophilic endohedral ¹³³Xe-fullerenols, [¹³³Xe@C₆₀(OH)_xand ¹³³Xe@C₇₀(OH)_x], were synthesized from hydrophobic endohedral ¹³³Xe-fullerenes. The yield of endohedral ¹³³Xe-fullerenols extracted in water was about 40% and 23% for C₆₀and C₇₀, respectively. The products stored in 0.9% NaCl solution at 20 °C were stable enough to be used in nuclear medicine.     

Response to “Comments on a Possible Transition to Solid‐Phase Homochirality”

As part of an ongoing discussion comparing models for the evolution of homochirality, we address the preceding Correspondence by Ribó and co‐workers. We demonstrate that our previous Concept article did not include errors concerning solubility behavior and we address the challenge of representing equilibrium phase behavior for systems of racemizing enantiomers. In addition we re‐emphasize the point that the homochiral state is not inherently more stable than the heterochiral state and we show that concerning this point the Ribó treatise misinterprets the Frank model for the evolution of homochirality.     

Improvements to CO<Subscript>2</Subscript> headspace biodegradability test

This study proposes changes to the design and evaluation of the CO₂ headspace test, which is used as a simple method for assessment of the complete biodegradability of surfactants. It presents a modified equation for the calculation of biodegradation. It is proposed that the solution of 7 mol L^?1 sodium hydroxide commonly used in the process involving alkalinisation of the vial contents be replaced with 15 mol L^?1 sodium hydroxide. The use of the higher hydroxide concentration leads to a significant reduction in the value of the blank CO₂ headspace test.     

A2E‐Mediated Photochemical Modification to Fibronectin and its Implications to Age‐Related Changes in Bruch's Membrane

Lipofuscin accumulates normally with age and is more pronounced in retinal dystrophies such as age‐related macular degeneration. The major bis‐retinoid component of lipofuscin is A2E. In addition to cell damage effects by A2E, we have previously demonstrated that blue‐light–mediated A2E leads to modifications in the basement membrane protein laminin. Therefore, the purpose of this study was to advance the understanding of A2E photooxidation effects on fibronectin, the major glycoprotein of Bruch's membrane. In this study, A2E was irradiated with blue light in the presence of a fibronectin peptide consisting of amino acids from the integrin binding region. The modification sites were identified via LC/MS. Our research indicated that blue light irradiation caused cleavage throughout the A2E molecule closest to the pyridinium ring, and attached to the fibronectin peptide preferentially at lysine and arginine residues. All of these reactions are similar to the Maillard reaction. Altogether this study suggests that blue‐light–irradiated A2E modifies peptides and forms advance glycation endproducts. Furthermore, these results can be used to identify modifications that occur in Bruch's membrane in vivo.     

Analytical Hartree–Fock wave functions subject to cusp and asymptotic constraints: He to Xe,Li+ to Cs+, H− to I−

Analytical, variational approximations to Hartree–Fock wave functions are constructed for the ground states of all the neutral atoms from He to Xe, the cations from Li⁺ to Cs⁺, and the stable anions from H⁻ to I⁻. The wave functions are constrained so that each atomic orbital agrees well with the electron–nuclear cusp condition and has good long‐range behavior. Painstaking optimization of the exponents and principal quantum numbers of the Slater‐type basis functions allows us to reach this goal while obtaining total energies that, at worst, are a few microHartrees above the numerical Hartree–Fock limit values. The wave functions are freely available by anonymous ftp from okapi.chem.unb.ca or upon request to the authors. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 491–497, 1999     

Routes to N‐vinyl‐nitroimidazoles and N‐vinyl‐deazapurines

The preparations of 4‐ and 5‐nitro‐1‐vinylimidazole ( 2 and 7 ) are described. Selective reduction of the nitro group using Fe/dil.HCl is achieved for the 4‐nitro derivative but this is not effective when ethoxymethylenemalononitrile is used to trap the amine. For 5‐nitroimidazole studies the N‐vinyl substituent is kept masked as a 2‐chloroethyl group, which remains unchanged during catalytic reduction of the nitro function (Pd/C), and is revealed by HCl elimination at a later stage. In this way, the 1‐deazapurine 13 and the tricyclic derivative 14 have been prepared.     

Generalization of the Copper to Late‐Transition‐Metal Transmetallation to Carbenes beyond N‐Heterocyclic Carbenes

Carbene transition‐metal complexes have become a prevalent family of catalysts enabling numerous organic transformations. Their facile synthetic access is a matter of great importance. To this end, the Cu^I‐NHC transfer methodology has emerged as a powerful alternative presenting attractive advantages over other methods. Herein, we report the remarkable ability of copper to transfer not only NHCs but also other types of carbenes such as abnormal NHCs (aNHCs), cyclic (alkyl)(amino)carbenes (CAACs), and mesoionic carbenes (MICs) to various transition metal precursors.     

促进知识素养化的教学——以“硝酸的性质”为例

以“铜制品抛光液”为情境素材,设计一系列的情境问题,旨在探究浓度、温度、酸度等因素对硝酸强氧化性的影响、硝酸的不稳定性及硝酸的贮输等核心内容。开展以化学实验为主的多种探究活动,学生在问题解决和探究过程中结构化“硝酸的性质”知识,利用结构化的知识评价铜制品抛光液的优缺点,并对此种抛光液提出合理的改进方案,促使知识素养化,落实学生的化学学科核心素养。     

A 2‐D‐HPLC‐CE platform coupled to ESI‐TOF‐MS to characterize the phenolic fraction in olive oil

A 2‐D‐HPLC/CE method was developed to separate and characterize more in depth the phenolic fraction of olive oil samples. The method involves the use of semi‐preparative HPLC (C18 column 250×10 mm, 5 μm) as a first dimension of separation to isolate phenolic fractions from commercial extra‐virgin olive oils and CE coupled to TOF‐MS (CE‐TOF‐MS) as a second dimension, to analyze the composition of the isolated fractions. Using this method, a large number of compounds were tentatively identified, some of them by first time, based on the information concerning high mass accuracy and the isotopic pattern provided by TOF‐MS analyzer together with the chemical knowledge and the behavior of the compounds in HPLC and CE. From these results it can be concluded that 2‐D‐HPLC‐CE‐MS provides enough resolving power to separate hundreds of compounds from highly complex samples, such as olive oil. Furthermore, in this paper, the isolated phenolic fractions have been used for two specific applications: quantification of some components of extra‐virgin olive oil samples in terms of pure fractions, and in vitro studies of its anti‐carcinogenic capacity.