60 research outputs found
Relationship between the Molecular Structure and Switching Temperature in a Library of Spin-Crossover Molecular Materials
Structureâfunction relationships relating the spin-crossover (SCO) midpoint temperature (T1/2) in the solid state are surveyed for 43 members of the iron(II) dipyrazolylpyridine family of SCO compounds. The difference between T1/2 in the solid state and in solution [ÎT(latt)] is proposed as a measure of the lattice contribution to the transition temperature. Negative linear correlations between the SCO temperature and the magnitude of the rearrangement of the coordination sphere during SCO are evident among isostructural or near-isostructural subsets of compounds; that is, a larger change in the molecular structure during SCO stabilizes the high-spin state of a material. Improved correlations are often obtained when ÎT(latt), rather than the raw T1/2 value, is considered as the measure of the SCO temperature. Different lattice types show different tendencies to stabilize the high-spin or low-spin state of the molecules they contain, which correlates with the structural changes that most influence ÎT(latt) in each case. These relationships are mostly unaffected by the SCO cooperativity in the compounds or by the involvement of any crystallographic phase changes. One or two materials within each subset are outliers in some or all of these correlations, however, which, in some cases, can be attributed to small differences in their ligand geometry or unusual phase behavior during SCO. A reinvestigation of the structural chemistry of [Fe(3-bpp)2][NCS]2·nH2O [3-bpp = bis(1H-pyrazol-3-yl)pyridine; n = 0 or 2], undertaken as part of this study, is also presented
A pHâSwitchable Triple HydrogenâBonding Motif
A stimuli responsive linear hydrogen bonding motif, capable of inâ
situ protonation and deprotonation, has been investigated. The interactions of the responsive hydrogen bonding motif with complementary partners were examined through a series of 1H NMR experiments, revealing that the recognition preference of the responsive hydrogen bonding motif in a mixture can be switched between two states
Crystallographic Structure, Intermolecular Packing Energetics, Crystal Morphology and Surface Chemistry of Salmeterol Xinafoate (Form I).
Single crystals of salmeterol xinafoate (form I), prepared from slow cooled supersaturated propan-2-ol solutions, crystallise in a triclinic PâŸ1 symmetry with two closely related independent salt pairs within the asymmetric unit, with an approximately double unit cell volume compared to the previously published crystal structure(1). Synthonic analysis of the bulk intermolecular packing confirms the similarity in packing energetics between the two salt pairs. The strongest synthons, as expected, are dominated by coulombic interactions. Morphological prediction reveals a plate-like morphology, dominated by the {001}, {010} and {100} surfaces, consistent with experimentally grown crystals. Though surface chemistry of the slow growing {001} face comprises of large sterically hindering phenyl groups, weaker coulombic interactions still prevail from the alcohol group present on the phenyl and hydroxymethyl groups. The surface chemistry of the faster growing {010} and {100} faces are dominated by the significantly stronger cation/anion interactions occurring between the carboxylate and protonated secondary ammonium ion groups. The importance of understanding the cohesive/adhesive nature of the crystal surfaces of an API, with respect to their interaction with other API crystals and excipients and how that may impact formulation design is highlighted
Structural optimization of reversible dibromomaleimide peptide stapling
Methods to constrain peptides in a bioactive αâhelical conformation for inhibition of proteinâprotein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible âstaplingâ methodology was described which exploits native cysteine or homocysteine residues spaced at the i and iâ+â4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X1 = LâCys and X5 = LâhCys in the context of the model peptide AcâX1AAAX5âNH2, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes
Crystallization Behavior and Crystallographic Properties of DL-Arabinose and DL-Xylose Diastereomer Sugars
Natural sugar molecules such as xylose and arabinose exhibit sweetness profiles similar to sucrose, which makes them a valuable alternative in low-calorie foods as well as excipients or cocrystallization agents in pharmaceutical formulations. Xylose and arabinose are also chiral diastereomers that can exhibit specific crystallization behavior. In this work, the solid-state landscapes of the chiral pairs of both xylose and arabinose have been investigated to determine whether racemic compounds or conglomerates are formed. Furthermore, single crystals of xylose and arabinose have been grown and characterized by X-ray diffraction and optical microscopy to study their crystallographic properties and relate them to the crystallization behavior. Differential scanning calorimetry (DSC) measurements were used to determine the phase diagrams of the two analyzed chiral systems. The solubilities of the different solid forms of xylose and arabinose were measured in different solvent mixtures by a thermogravimetric method. An analysis was conducted to assess the main thermodynamic parameters and the activity coefficients of the compounds in solution. Finally, slurry experiments in a 50:50 w/w ethanol/water solvent have also been performed to determine the relative stability of each solid form and the kinetics of transformation in this solvent mixture. It was found that dl-arabinose crystallizes as a stable racemic compound, which transforms quickly from its constituent enantiomers when in solution; whereas d- and l-xylose molecules crystallize separately as a conglomerate
Tethered N-Heterocyclic Carbene-Carboranyl Silver Complexes for Cancer Therapy
Silver complexes of tethered N-heterocyclic carbene-carboranyl ligands have been prepared and fully characterized. The first example of silver bonded directly to the cage of o-carborane has been identified in the solid state. The presence of a carboranyl N substituent on the N-heterocyclic carbene significantly enhances the in vitro cytotoxicity of the silver complex against HCT116 p53+/+ and HCT116 p53â/â colon cancer cells in comparison to a phenyl derivative. Conversely, the presence of a carboranyl on the backbone of a xanthine-derived N-heterocyclic carbene decreases the in vitro cytotoxicity of the silver complex in comparison to its phenyl derivative. Stability studies on the xanthine-derived ligands and complexes show that decomposition via deboronation occurs in hydrous dimethyl sulfoxide, which may attribute to the contrasting in vitro behaviors of the carborane-containing complexes
Bis(N-picolinamido)cobalt(II) Complexes Display Antifungal Activity toward Candida albicans and Aspergillus fumigatus
This report highlights the synthesis and characterization of ten new bis(N-picolinamido)cobalt(II) complexes of the type [(L)2CoX2]0/2+, whereby L=N-picolinamide ligand and X=diisothiocyanato (âNCS), dichlorido (âCl) or diaqua (âOH2) ligands. Single crystal X-ray (SC-XRD) analysis for nine of the structures are reported and confirm the picolinamide ligand is bound to the Co(II) center through a neutral N,O binding mode. With the addition of powder X-ray diffraction (PXRD), we have confirmed the cis and trans ligand arrangements of each complex. All complexes were screened against several fungal species and show increased antifungal activity. Notably, these complexes had significant activity against strains of Candida albicans and Aspergillus fumigatus, with several compounds exhibiting growth inhibition of >80â%, and onecompound inhibiting Aspergillus fumigatus hyphal growth by >90â%. Conversely, no antifungal activity was exhibited toward Cryptococcus neoformans and no cytotoxicity towards mammalian cell lines
Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp3-Rich Compounds With Distinct Phenotypic Effects
A âtop downâ scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity-generating oxidative dearomatisation. Eighteen structurally-distinct, sp3-rich scaffolds were accessed from the parent tricycle through ring addition, cleavage and expansion strategies. Biological screening of a small compound library based on these scaffolds using the cell-painting assay demonstrated distinctive phenotypic responses engendered by different library members, illustrating the functional as well as structural diversity of the compounds
Modular Synthesis of Bicyclic Twisted Amides and Anilines
Bridged amides and anilines display interesting properties owing to perturbation of conjugation of the nitrogen lone-pair with the adjacent Ï-system. A convergent approach to diazabicyclic scaffolds which contain either twisted amides or anilines is described, based on the photocatalysed hydroamination of cyclic enecarbamates and subsequent cyclisation. The modular nature of the synthesis allows for variation of the degree of âtwistâ and hence the properties of the amides and anilines
Correction: Heteroleptic iron(ii) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands â the interplay of two different ligands on the metal ion spin state
Correction for âHeteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands â the interplay of two different ligands on the metal ion spin stateâ by Namrah Shahid et al., Dalton Trans., 2022, 51, 4262â4274, DOI: 10.1039/d2dt00393g
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