The Effect of the Spacer of Bis(biurea) Ligands on the Structure of A2L3‐type (A=anion) Phosphate Complexes

By tuning the length and rigidity of the spacer of bis(biurea) ligands L, three structural motifs of the A₂L₃ complexes (A represents anion, here orthophosphate PO₄^3?), namely helicate, mesocate, and mono‐bridged motif, have been assembled by coordination of the ligand to phosphate anion. Crystal structure analysis indicated that in the three complexes, each of the phosphate ions is coordinated by twelve hydrogen bonds from six surrounding urea groups. The anion coordination properties in solution have also been studied. The results further demonstrate the coordination behavior of phosphate ion, which shows strong tendency for coordination saturation and geometrical preference, thus allowing for the assembly of novel anion coordination‐based structures as in transition‐metal complexes.     

A systematic density functional theory study of the electronic structure of bulk and (001) surface of transition-metals carbides

A systematic study of the bulk and surface geometrical and electronic properties of a series of transition-metal carbides (TMC with TM = Ti, V, Zr, Nb, Mo, Hf, Ta, and W) by first-principles methods is presented. It is shown that in these materials the chemical bonding is strongly covalent, the cohesive energies being directly related to the bonding-antibonding gap although the shift of the center of the C(2s) band related peak in the density of states with respect to diamond indicates that some metal to carbon charge transfer does also take place. The (001) face of these metal carbides exhibits a noticeable surface rumpling which grows along the series. It is shown that neglecting surface relaxation results in very large errors on the surface energy and work function. The surface formation induces a significant shift of electronic energy levels with respect to the corresponding values in the bulk. The extent and nature of the shift can be understood from simple bonding-antibonding arguments and is enhanced by the structural rippling of this surface.     

Inclusion of molybdenocene dichloride (Cp2MoCl2) in 2-hydroxypropyl- and trimethyl-β-cyclodextrin: Structural and biological properties

Organometallic-cyclodextrin inclusion compounds were obtained by the treatment of molybdenocene dichloride (Cp₂MoCl₂) with the modified cyclodextrins (CDs) heptakis-2,3,6-tri-O-methyl-β-CD (TRIMEB) and 2-hydroxypropyl-β-CD (HPβCD) in aqueous solution. The products were isolated by liophilisation and characterised in the solid-state by powder XRD, thermogravimetric analysis, Raman and FTIR spectroscopy, and ¹³C CP MAS NMR spectroscopy. The results are consistent with inclusion of Cp₂MoCl₂, rather than hydrolysis products such as [Cp₂Mo(H₂O)X]⁺ (X = Cl, OH) or [Cp₂Mo(H₂O)₂]²⁺. The pure non-included metallocene Cp₂MoCl₂ and its inclusion compounds with unmodified β-CD, TRIMEB and HPβCD were screened for their potential antiproliferative and cytotoxic activity, in both human cancer and healthy cell lines. Inclusion in CD was found to enhance the cytotoxic effect of Cp₂MoCl₂, with the TRIMEB adduct displaying the highest anti-tumour activity, along with the lowest toxicity towards non-neoplastic cells.     

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).     

Complexes with ambidentate ligands derived from pyridine and pyrimidine-Part 1. Cyclic nickel(II) complexes

Summary In a series of hexacoordinated nickel(II) complexes, prepared from thio-, sulphinyl, and carbonyl derivatives of pyridine and pyrimidine, the endocyclic N-atom was always the preferred basic site; the sulphinyl O-atom was also a donor centre, forming 5-membered heterocycles, whereas the carbonyl O-atom did not bond to the metal. Alkylthio derivatives did not react, unlike thiolate anions, which form N, S-bonded 4-membered rings. On the other and 2,2-bis(pyridyl)ketone bonded exclusively through the N-atoms, forming 6-membered cycles.     

Thermochemical studies of phthalimide and two N-alkylsubstituted phthalimides (ALKYL=ETHYL AND n-PROPYL)

The standard (p⁰=0.1 MPa) molar enthalpies of formation, Δ_fH_m⁰, for crystalline phthalimides: phthalimide, N-ethylphthalimide and N-propylphthalimide were derived from the standard molar enthalpies of combustion, in oxygen, at the temperature 298.15 K, measured by static bomb-combustion calorimetry, as, respectively, – (318.0±1.7), – (350.1±2.7) and – (377.3±2.2) kJ mol^–1. The standard molar enthalpies of sublimation, Δ_cr^gH_m⁰, at T=298.15 K were derived by the Clausius-Clapeyron equation, from the temperature dependence of the vapour pressures for phthalimide, as (106.9±1.2) kJ mol^–1 and from high temperature Calvet microcalorimetry for phthalimide, N-ethylphthalimide and N-propylphthalimide as, respectively, (106.3±1.3), (91.0±1.2) and (98.2±1.4) kJ mol^–1. The derived standard molar enthalpies of formation, in the gaseous state, are analysed in terms of enthalpic increments and interpreted in terms of molecular structure.