The barriers of torsional isomerization of 13 substituted biphenyls, ranging from 7.4 to 44 kcal mol(-1), were calculated using 9 density functionals (the BP86 and B97D GGAs, the meta-GGA TPSS, ...hybrids B3LYP, PBE0, ωB97XD, BMK and M06-2X, as well as the double-hybrid B2PLYP), some combined with D and D3 corrections for dispersive interactions, and results were compared with experimental data. As attractive dispersive interactions between substituents had a significant impact on the geometries and stabilities of the ground and transition states of the torsional isomerization pathways, the B3LYP-D, B97-D and TPSS-D3 functionals were identified as the most promising methods, and were used to determine the torsional barriers of 33 other substituted biphenyls with known Gibbs energies of activation (6.0 to 45 kcal mol(-1)). Throughout the 46-member ensemble, results were very accurate relative to experimental values (mean deviation between -0.38 and 0.24 kcal mol(-1)), and narrow distributions of errors were obtained (root-mean-square deviations between 0.14 and 0.16 kcal mol(-1); mean absolute deviations ranging from 0.61 to 0.75 kcal mol(-1)), as long as (1) large triple-ζ basis sets were used, (2) all conformations were screened at these levels of theory, (3) electronic energies were corrected with zero-point energies and entropic contributions, and (4) solvation effects were taken into account for biphenyl derivatives bearing charged ortho-substituents. With its simple procedures, this study is intended as a benchmark for future determinations of torsional barriers of various biphenyl derivatives.
Platinum terpyridyl complexes, stacked on top of one another and secured as dimers with cucurbit8uril (CB8) in aqueous medium, were functionalized quantitatively and
in situ
with a pair of ...pentapeptides Phe-(Gly)
3
-Cys by grafting their cysteine residues to the Pt centers. The resulting CB8·(Pt·peptide)
2
assemblies were used to target secondary hosts CB7 and CB8
via
their pair of phenylalanine residues, again
in situ
. A series of well-defined architectures, including a supramolecular "pendant necklace" with hybrid head-to-head and head-to-tail arrangements inside CB8, were obtained during the self-sorting process after combining only 3 or 4 simple building units.
A platinum terpyridyl complex, pentapeptide Phe-(Gly)
3
-Cys and cucurbit8uril assemble into a "pendant necklace" with hybrid head-to-head and head-to-tail arrangements in aqueous medium.
The ability to mimic the activity of natural enzymes using supramolecular constructs (artificial enzymes) is a vibrant scientific research field. Herein, we demonstrate that cucurbit7uril (CB7) can ...catalyse Diels–Alder reactions for a number of substituted and unreactive N‐allyl‐2‐furfurylamines under biomimetic conditions, without the need for protecting groups, yielding powerful synthons in previously unreported mild conditions. CB7 rearranges the substrate in a highly reactive conformation and shields it from the aqueous environment, thereby mimicking the mode of action of a natural Diels–Alderase. These findings can be directly applied to the phenomenon of product inhibition observed in natural Diels–Alderase enzymes, and pave the way toward the development of novel, supramolecular‐based green catalysts.
Copycat.: Cucurbit7uril (CB7) is able to catalyse Diels–Alder reactions for substituted and otherwise unreactive N‐allyl‐2‐furfurylamines, thus imitating the role of a Diels–Alderase enzyme. Despite the reaction products exhibiting higher binding affinities for CB7 than their reactants, Diels–Alder reactions can indeed proceed under mild and biomimetic catalytic conditions.
Abstract
Complexes containing rare-earth ions attract great attention for their technological applications ranging from spintronic devices to quantum information science. While charged rare-earth ...coordination complexes are ubiquitous in solution, they are challenging to form on materials surfaces that would allow investigations for potential solid-state applications. Here we report formation and atomically precise manipulation of rare-earth complexes on a gold surface. Although they are composed of multiple units held together by electrostatic interactions, the entire complex rotates as a single unit when electrical energy is supplied from a scanning tunneling microscope tip. Despite the hexagonal symmetry of the gold surface, a counterion at the side of the complex guides precise three-fold rotations and 100% control of their rotational directions is achieved using a negative electric field from the scanning probe tip. This work demonstrates that counterions can be used to control dynamics of rare-earth complexes on materials surfaces for quantum and nanomechanical applications.
LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on ...days 1 to 7 of a 21-day cycle.
Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m(2)): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasma LBH589 concentrations were assayed.
Four dose-limiting toxicities (grade 3 QTcF prolongation) were observed, four at 14.0 mg/m(2) and one at 11.5 mg/m(2). QTcF prolongation was asymptomatic and reversed on LBH589 discontinuation. Other potentially LBH589-related toxicities included nausea (40%), diarrhea (33%), vomiting (33%), hypokalemia (27%), loss of appetite (13%), and thrombocytopenia (13%). In 8 of 11 patients with peripheral blasts, transient reductions occurred with a rebound following the 7-day treatment period. H3 acetylation increase was significant in B-cells (CD19(+); P = 0.02) and blasts (CD34(+); P = 0.04). The increase in H2B acetylation was highest in CD19(+) and CD34(+) cells 3.8-fold (P = 0.01) and 4.4-fold (P = 0.03), respectively. The median acetylation of histones H2B and H3 in CD34(+) and CD19(+) cells significantly increased on therapy as did apoptosis in CD14(+) cells. Area under the curve increased proportionally with dose with a terminal half-life of approximately 11 hours.
Intravenous administration of LBH589 was well tolerated at doses <11.5 mg/m(2) with consistent transient antileukemic and biological effects.
In the absence of industry data, organisms, and researchers leverage free and available data, specifically building and demolition permits. Geospatial processing is essential to integrate information ...from various files into a single GIS layer containing all relevant attributes for analysis. This article proposes a Geographic Information System (GIS) processing model aimed at monitoring construction and demolition dynamics in the European metropolis of Lille to quantify the urban production of mineral waste from buildings. Author methodology is based on that that the deposit potential can be analyzed using the observation of the spatiotemporal dynamics of building and demolition permits. The results demonstrate that combining construction and demolition (C&D) permits with other GIS layers allows us to produce data to quantify demolition surfaces per year in a given French area. The applicability of this methodology extends to all French regions, providing insights into the impact of crises on deconstruction activities and C&D waste generation. The study focuses on C&D French public data bases (French government and European Metropolis of Lille) attributed to the region (area) of the European Metropolis of Lille (MEL) between 2013 and 2022. Some data for 2022 were incomplete due to ongoing treatment, emphasizing the importance of understanding the dynamics of demolition rates or surfaces to identify data gaps or errors. Historical trajectories of C&D permits were quantified and analyzed, revealing over 21,000 permits granted from 2013 to 2022, categorized by site type (new construction, rehabilitations, prior declarations, and demolitions). Construction sites during this period covered approximately 3,345,948 m2, constituting 20% of the MEL’s building stock, while demolition sites amounted to 1,977,911 m2, equivalent to 5% of the total area of buildings in the metropolis. Employing GIS allowed for a spatial analysis, visualizing data by municipality, urban fabric, and year. The analysis highlighted territories with high and low potential for demolition and construction, as well as the most impacted urban fabrics and dynamic periods. The article discusses potential crisis impacts (e.g., COVID-19 or economic downturns) and the implications of incomplete data. Finally, the study demonstrates how these findings can be utilized to quantify C&D waste, leveraging GIS and the production rate calculation method (GRC).
To maximize Coulombic interactions, cucurbit8uril (CB8) typically forms ternary complexes that distribute the positive charges of the pair of guests (if any) over both carbonylated portals of the ...macrocycle. We present here the first exception to this recognition pattern. Platinum(II) acetylides flanked by 4′‐substituted terpyridyl ligands (tpy) form 2:1 complexes with CB8 in an exclusively stacked head‐to‐head orientation in a water/acetonitrile mixture. The host encapsulates the pair of tpy substituents, and both positive Pt centers sit on top of each other at the same CB8 rim, leaving the other rim free of any interaction with the guests. This dramatic charge imbalance between the CB8 rims would be electrostatically penalizing, were it not for allosteric π–π interactions between the stacked tpy ligands, and possible metal‐metal interactions between both Pt centers. When both tpy and acetylides are substituted with aryl units, the metal‐ligand complexes form 2:2 assemblies with CB8 in aqueous medium, and the directionality of the assembly (head‐to‐head or head‐to‐tail) can be controlled, both kinetically and thermodynamically.
A novel recognition pattern between a pair of positively charged guests and cucurbit8uril is presented.
Primary fieldworks precede the formalisation of geographical knowledges, but not only. It also refers to a somewhat vague notion that raises the question of the antecedence of fieldwork in the ...researcher’s relationship to the knowledge he or she develops. Fieldwork is a polysemous term that has a multitude of definitions depending on the scientific disciplines and methodologies, the themes or the objects/subjects studied. The fieldwork is therefore not only a portion of the earth’s surface under study, but a spatial context, an environment, an interplay between its physical, societal, cultural and sensory dimensions, etc. This article is a (self)reflective contribution on the importance of fieldwork for Geography. It addresses the multitude of scientific fieldworks, the concept of primary fieldwork and a reflection on the interdependence between methodology and fieldwork for the production of geographical knowledge.
PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, ...VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase, and the c-kit protein tyrosine kinase. In this phase I dose-escalating study, PTK/ZK was administered bid to exploit the theoretical advantage of maintaining constant drug levels above a threshold known from preclinical data to interfere with VEGF receptor signaling.
Forty-three patients with advanced cancers received single-agent PTK/ZK at doses of 150 to 1,000 mg orally bid. Assessments for safety and pharmacokinetics were performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic marker of response.
At 1,000 mg bid, the dose-limiting toxicity of reversible grade 3 lightheadedness was observed. Dose-related grade 3 fatigue and vomiting were observed but these were not dose-limiting. Pharmacokinetic data confirmed that PTK/ZK exposure increased with increasing dose up to 500 mg bid and appeared to plateau at higher doses. A greater than 40% reduction in the DCE-MRI bidirectional transfer constant (K(i)) at day 2 predicted for nonprogression of disease.
The maximum-tolerated oral dose of PTK/ZK is 750 mg orally bid. DCE-MRI and pharmacokinetic data indicate that PTK/ZK >/= 1,000 mg total daily dose is the biologically active dose.
Cucurbit6-, cucurbit7-, and cucurbit6uril cavitands can be aligned along a spermine derivative axle in a well-defined, kinetically favored sequence at room temperature, and can undergo a ...reorganization toward a more stable 4pseudorotaxane bearing three cucurbit6uril units upon thermally induced scrambling.
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