Gregory M. Ferrence

Acid-catalyzed condensation of N-alkyltripyrranes with a cyclopentadiene trialdehyde, followed by oxidation with aqueous ferric chloride solutions, gave unusual tripyrrolic byproducts in addition to previously reported carbaporphyrins and oxycarbaporphyrins. These stable nonaromatic structures incorporate aldehyde substituents, macrocyclic ketones, two conjugated pyrrole units, and a pyrrolo[1,2-a]pyrrole moiety. The NMR and UV-vis data were consistent with a nonaromatic system, and single-crystal X-ray diffraction confirmed that these structures are highly distorted. Structural characterization of a related aromatic carbaporphyrin triketone was also accomplished.

Phenaliporphyrin, a new aromatic benziporphyrin derivative, has been synthesized from an annulated cyclopropane dialdehyde intermediate. Corey-Chaykovsky cyclopropanation of dimethyl acenaphthylene-1,2-dicarboxylate gave a cyclopropane diester, and this was converted to the corresponding bis-Weinreb amide. Reduction with lithium aluminum hydride afforded an unstable dialdehyde and subsequent acid-catalyzed condensation with a tripyrrane dicarboxylic acid, followed by oxidation with aqueous ferric chloride, gave the targeted porphyrinoid system. This involves ring expansion of the acenaphthylene precursor to generate the phenalene unit. Phenaliporphyrin exhibits a porphyrin-like UV-vis spectrum with a Soret band at 443 nm and a relatively intense Q-band at 601 nm. The proton NMR spectrum demonstrated that the system has a strong diamagnetic ring current, and the external meso-protons showed up downfield at 9.64 and 9.34 ppm while the internal C-H appeared upfield at -6.48 ppm. Although DFT calculations show that the phenalene ring is twisted to relieve steric interactions, single crystal X-ray diffraction analysis indicated that the macrocycle is nearly planar. The discrepancy was attributed to crystal packing forces and a distorted conformation is likely to be favored in solution. The aromatic properties for phenaliporphyrin were confirmed by nucleus independent chemical shift (NICS) calculations and anisotropy of induced current density plots.

Applications of lanthanide chemistry have been successful in metallics and the petroleum industry. In the medical realm, lanthanides have shown utility in radiotherapy agents, photodynamic therapy agents, and magnetic resonance imaging (MRI) contrast agents. The lanthanide group elements have a few known biological roles, notably among some bacteria and the yeast Saccharomyces cerevisiae, which have been used as models for changes in gene expression. However, the systematic effects of lanthanide nitrates on eukaryotic cell model systems have not yet been reported. This study presents the first documented effects on cell viability, after acute incubations of various lanthanide nitrate salts, using axenic C6 glial or PC12 neuronal cells in vitro. Cultures were exposed to a 1 mM concentration of lanthanide nitrate salts for 24 h. In comparison to the saline control, several cultures demonstrated significantly lower cell viability, as measured by the MTT viability assay. Data were analyzed as an average absorbance of n = 4 replicate samples, corrected for the average absorbance of cell-free blanks. The reported results were normalized to the average of the saline control cells. Among the 13 lanthanides tested, Praseodymium, Holmium, Erbium, Thulium, and Ytterbium nitrates exhibited the most pronounced inhibitory effects, resulting in over 40% reduction in cell viability at 1 mM for either or both cell types. Recovery after lanthanide exposure also was cell-type-dependent as well as lanthanide-type-dependent, with Lutetium having the greatest effect on both cell types. PC12 cells displayed greater sensitivity for inhibition than the C6 cells with some of the lanthanides but not all. Furthermore, the controls of sodium nitrate and calcium nitrate showed only modest discernible impacts on cell viability for PC12 and C6 cells, highlighting the role of the lanthanides in influencing cell viability.

Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g., P1, P1', P2, and P2') of the darunavir framework have been structurally modified. An alternate route for the synthesis of darunavir and three related P1 and P1' derivatives has been developed. This synthetic pathway involves the use of a Crimmins titanium tetrachloride-mediated oxazolidine-2-thione-guided asymmetric glycolate aldol addition reaction. The resultant aldol adduct introduces the P1 fragment of darunavir via an aldehyde. Transamidation with a selected amine (isobutylamine or 2-ethyl-1-butylamine) to cleave the auxiliary yields an amide wherein the P1' component is introduced. From this stage, the amide is reduced to the corresponding β-amino alcohol and the substrate is then bis-nosylated to introduce the requisite p-nitrobenzenesulfonamide component and activate the secondary alcohol for nucleophilic substitution. Treatment with sodium azide yielded the desired azides, and the deprotection of the p-methoxyphenoxy group is achieved with the use of ceric ammonium nitrate. Finally, hydrogenation to reduce both the aniline and azide functionalities with concurrent acylation yields darunavir and its derivatives.

The Cambridge Structural Database (CSD) is a collection of over one million experimental three-dimensional structures obtained through crystallographic analyses. These structures are determined by crystallographers worldwide and undergo curation and enhancement by scientists at the Cambridge Crystallographic Data Centre (CCDC) prior to their addition to the database. Though the CSD is substantial and contains widespread chemical diversity across organic and metal–organic compounds, it is estimated that a significant proportion of crystal structures determined are not published or shared through the peer-reviewed journal mechanism. To help overcome this, scientists can publish structures directly through the database as CSD Communications and these structural datasets are made publicly available alongside structures associated with scientific articles. CSD Communications contribute to the collective crystallographic knowledge as nearly two thirds are novel structures that are not otherwise available in the scientific literature. The primary benefits of sharing data through CSD Communications include the long-term preservation of scientific data, the strengthening of a widely data-mined world repository (the CSD), and the opportunity for scientists to receive recognition for their work through a formal and citable data publication. All CSD Communications are assigned unique digital object identifiers (DOIs). Contributions as CSD Communications currently comprise about 3.89% of the total CSD entries. Each individual CSD Communication is free to view and retrieve from the CCDC website.

The evolution of high virulence bacterial strains has necessitated the development of novel therapeutic agents to treat resistant infections. Metal-based therapeutics represent a promising avenue for advancement, given their structural variability and unique modes of action relative to classical organic molecules. One strategy that has seen marked success is the incorporation of ferrocene into the framework of established antibacterial agents, while ruthenium-based complexes have also shown promise as bioactive compounds. This work focused on the preparation of novel ruthenium(II)-arene complexes containing Schiff base ligands with an attached ferrocene, and evaluation of their antibacterial activity. Structure–activity relationships identified the importance of having a phenyl group between the Schiff base imine and the appended ferrocene. This complex, C2, showed prominent activity against several clinically relevant bacterial strains, including a minimum inhibitory concentration of 16 μg mL⁻¹ for methicillin-resistant Staphylococcus aureus (MSRA). Overall, the results of this study represent a promising new lead for future development of novel antibacterial agents.

Treatment of β-hydroxy-α-p-methoxyphenoxy carboxylic acids derived from the asymmetric glycolate aldol addition reaction with p-nitrobenzenesulfonyl chloride yielded divergent results depending on the nature of the β-substituent of the carboxylic acid. Substrates bearing either alkyl substituents (R = -n-butyl, -n-octyl, -benzyl, isopropyl, -tert-butyl) or aryl systems bearing electron-withdrawing substituents (R = -p-C₆H₄Cl, -p-C₆H₄Br, -p-C₆H₄NO₂) yielded β-lactones. In contrast, α-p-methoxyphenoxy-β-hydroxycarboxylic acids bearing electron-donating aryl groups or the sterically demanding 2-naphthyl group formed (Z)-alkenes.

The formation, structure, and photoreactivity of a pair of silver(I) complexes based upon either trifluoromethanesulfonate [Ag(CF₃SO₃)] or p-toluenesulfonate [Ag(C₇H₇SO₃)] anions along with the ester-based reactant molecule trans-1-(4-methylbenzoate)-2-(4-pyridyl)ethylene (1) are reported. In both complexes, silver(I) ions form coordinated covalent bonds to the 4-pyridyl group on the olefin containing reactant molecule and due to either argentophilic interactions or close packing of a pair of silver(I) ions ultimately places a pair of carbon-carbon bonds (C = C) on neighboring molecules of 1 in a suitable position to undergo a solid-state [2 + 2] cycloaddition reaction. In particular, the complexes [Ag(CF₃SO₃)(1)₂]·CH₃CN and [Ag₂(C₇H₇SO₃)₂(1)₄] both undergo a quantitative photoreaction to yield the head-to-head photoproduct rctt-1,2-bis(4-methylbenzoate)-3,4-bis(4-pyridyl)cyclobutane (2) upon exposure to ultraviolet light. Graphical Abstract

Structural diversity is achieved in a series of halogen-bonded co-crystals based upon cooperative non-covalent interactions and the synthetic feed of the components.