A novel Ni(4) complex exhibiting microsecond quantum tunneling of the magnetization

A highly asymmetric Ni(II) cluster [Ni(4)(OH)(OMe)(3)(Hphpz)(4)(MeOH)(3)](MeOH) (1) (H(2)phpz=3-methyl-5-(2-hydroxyphenyl)pyrazole) has been prepared and its structure determined by means of single-crystal X-ray diffraction by using synchrotron radiation. Variable-temperature bulk-magnetization measurements show that the complex exhibits intramolecular-ferromagnetic interactions leading to a spin ground state S=4 with close-lying excited states. Magnetization and high-frequency EPR measurements suggest the presence of sizable Ising-type magnetic anisotropy, with zero-field splitting parameters D=-0.263 cm(-1) and E=0.04 cm(-1) for the spin ground state, and an isotropic g value of 2.25. The presence of both axial and transverse anisotropy was confirmed through low-temperature specific heat determinations down to 300 mK, but no slow relaxation of the magnetization was observed by AC measurements down to 1.8 K. Interestingly, AC susceptibility measurements down to temperatures as low as 23 mK showed no indication of slow relaxation of the magnetization in 1. Thus, despite the presence of an anisotropy barrier (U approximately 4.21 cm(-1) for the purely axial limit), the magnetization relaxation remains extremely fast down to the lowest temperatures. The estimated quantum tunneling rate, Gamma>0.667 MHz, makes this complex a prime candidate for observation of coherent tunneling of the magnetization.     

Determination of alpha-amylase inhibitor activity of phaseolamin from kidney bean (Phaseolus vulgaris) in dietary supplements by HPAEC-PAD

Some dietary supplements, so-called 'starch-blockers', used to control overweight, are based on the protein concentrate of the kidney bean, known to contain high levels of the alpha-amylase inhibitor phaseolamin, which may hinder the digestion of complex carbohydrates, thereby promoting or supporting weight loss. Currently, methods to determine the levels of alpha-amylase inhibitor are based on the measurement of alpha-amylase activity using colorimetric methods that cannot be applied to dietary supplements because they are complex mixtures of different ingredients that may interfere with the measurement. The aim of this study was to develop an alternative method to determine the level of phaseolamin in dietary supplements, using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) to measure the amount of maltose resulting from the action of the enzyme porcine alpha-amylase on soluble starch in the presence and absence of the inhibitor. The assay described proved sensitive and accurate for use with both dietary supplements and raw materials.     

Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF₃ groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7 – 14 ). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by ¹H‐, ¹³C‐, and ¹⁹F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF₃ groups, thus introduced, may be replaced by H (Na/NH₃), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed.     

Mononuclear manganese(III) complexes as building blocks for the design of trinuclear manganese clusters: study of the ligand influence on the magnetic properties of the [Mn3(mu3-O)](7+) core

The synthesis, crystal structure, and magnetic properties of three new manganese(III) clusters are reported, [Mn 3(mu 3-O)(phpzH) 3(MeOH) 3(OAc)] (1), [Mn 3(mu 3-O)(phpzMe) 3(MeOH) 3(OAc)].1.5MeOH (2), and [Mn 3(mu 3-O)(phpzH) 3(MeOH) 4(N 3)].MeOH (3) (H 2phpzH = 3(5)-(2-hydroxyphenyl)-pyrazole and H 2phpzMe = 3(5)-(2-hydroxyphenyl)-5(3)-methylpyrazole). Complexes 1- 3 consist of a triangle of manganese(III) ions with an oxido-center bridge and three ligands, phpzR (2-) (R = H, Me) that form a plane with the metal ions. All the complexes contain the same core with the general formula [Mn 3(mu 3-O)(phpzR) 3] (+). Methanol molecules and additional bridging ligands, that is, acetate (complexes 1 and 2) and azide (complex 3), are at the terminal positions. Temperature dependent magnetic susceptibility studies indicate the presence of predominant antiferromagnetic intramolecular interactions between manganese(III) ions in 1 and 3, while both antiferromagnetic and ferromagnetic intramolecular interactions are operative in 2.     

Front Cover: Katritzky Salts for the Synthesis of Unnatural Amino Acids and Late-Stage Functionalization of Peptides (Eur. J. Org. Chem. 12/2023)

Peptide drug discovery often benefits from the large structural diversity permitted by unnatural amino acids (UAAs). Indeed, numerous approved peptide drugs include UAAs in their sequences. Therefore, innovative chemical approaches either to synthesize UAAs or to allow late-stage functionalization of peptides are emerging themes in peptide drug discovery. Thanks to the recent advances in deaminative strategies using alkylpyridiniums salts, often referred to as Katritzky salts, a variety of radical alkylation methods have been developed. In recent years the use of Katritzky salts have become popular in peptide chemistry due to their ease of preparation from a primary amine, which is a predominant functional group in amino acids. This review highlights the progress that has been made by using Katritzky salts in the synthesis of UAAs, late-stage peptide functionalization, and peptide macrocyclization.     

Isothiourea‐Catalysed Acylative Kinetic Resolution of Aryl–Alkenyl (sp2 vs. sp2) Substituted Secondary Alcohols

The non‐enzymatic acylative kinetic resolution of challenging aryl–alkenyl (sp² vs. sp²) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl–alkenyl substituted alcohols has been evaluated, with either electron‐rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (S=2–1980). The use of this protocol for the gram‐scale (2.5 g) kinetic resolution of a model aryl–vinyl (sp² vs. sp²) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 e.r.     

Properties and limits of some essential oils: chemical characterisation,antimicrobial activity,interaction with antibiotics and cytotoxicity

Because of the emergence of multi-drug resistance bacteria and fungi, alternatives to conventional antimicrobial therapy are needed. This study aims to evaluate in vitro the antimicrobial activity of: Mirtus communis, Coriandrum sativum, Pelargonium capitatum, Cuminum cyminum, Ocimum basilicum, Citrus aurantium amara, Cymbopogon. winterianus, Cymbopogon martini, Salvia sclarea, Melaleuca alternifolia and Mentha suaveolens essential oils on bacteria and fungi, in relation to their chemical composition. The potential interaction of M. alternifolia (TTO), C. sativum (CDO) and M. suaveolens (EOMS) essential oils when used in combination with gentamicin and fluconazole has been evaluated. The results obtained showed a synergic effect on some bacteria and fungi, with FICI values ≤5. The cytotoxicity of TTO, CDO and EOMS was investigated towards HeLa cells. Only EOMS did not result cytotoxic at the active concentrations on micro-organisms. Further studies are necessary to obtain optimal ratios and dosing regimens for higher therapeutic efficacy and to decrease toxicological profiles.     

Oxygen-17 hyperfine structures in the pure rotational spectra of SrO, SnO, BaO, HfO and ThO

Hyperfine structures arising from the couplings of the nuclear spin angular momentum of (17)O (I = 5/2) with the end over end rotation of several metal-containing diatomic monoxides have been observed using a Fourier transform microwave spectrometer. The molecules have been produced by reacting (17)O(2) with laser ablated metal atoms. The oxygen-17 nuclear quadrupole coupling constants have been determined for the title molecules and are interpreted in terms of a simple Townes-Dailey model. Also, the oxygen-17 nuclear spin-rotation constants have been determined and used to calculate the oxygen-17 shieldings for each molecule.