Akhtarlindsay3865

Bioorthogonal decaging reactions for controllable drug activation within complex biological systems are highly desirable yet extremely challenging. Herein, we find a new class of Pt(II)-triggered bioorthogonal cleavage reactions in which Pt(II) but not Pt(IV) complexes effectively trigger the cleavage of O/N-propargyl in a variety of ranges of caged molecules under biocompatible conditions. Based on these findings, we propose a general strategy for integrated bioorthogonal prodrugs and accordingly design a prodrug 16, in which a Pt(IV) moiety is covalently connected with an O2-propargyl diazeniumdiolate moiety. It is found that 16 can be specifically reduced by cytoplasmic reductants in human ovarian cancer cells to liberate cisplatin, which subsequently stimulates the cleavage of O2-propargyl to release large amounts of NO in situ, thus generating synergistic and potent tumor suppression activity in vivo. Therefore, Pt(II)-triggered depropargylation and the integration concept might provide a general strategy for broad applicability of bioorthogonal cleavage chemistry in vivo.Multiconfiguration pair-density functional theory (MC-PDFT) is a multireference method that can be used to calculate excited states. However, MC-PDFT potential energy surfaces have the wrong topology at conical intersections because the last step of MC-PDFT is not a diagonalization of a model-space Hamiltonian matrix, as done in, for example, multistate second-order perturbation theory (MS-CASPT2). We have previously proposed methods that solve this problem by diagonalizing a model-space effective Hamiltonian matrix, where the diagonal elements are MC-PDFT energies for intermediate states, and the off-diagonal elements are evaluated by wave function theory. One previous method is called variational multistate PDFT (VMS-PDFT), whose intermediate states maximize the trace of the effective Hamiltonian, namely, the sum of the MC-PDFT energies of the model-space states; the VMS-PDFT is very robust but is more computationally expensive than another method, extended multistate PDFT (XMS-PDFT), in which the transformation to intermediate states is accomplished without needing any density functional evaluations. However, although VMS-PDFT was accurate in all cases tested, XMS-PDFT was accurate in only some of them. In the present paper, we propose a new method, called compressed-state multistate PDFT (CMS-PDFT), that is as efficient as XMS-PDFT and as accurate as VMS-PDFT. The new method maximizes the trace of the classical Coulomb energy of the intermediate states such that the electron densities of the intermediate states are compressed. We show that CMS-PDFT performs robustly even where XMS-PDFT fails.To understand and treat immunology-related diseases, a comprehensive, unbiased characterization of major histocompatibility complex (MHC) peptide ligands is of key importance. Preceding the analysis by mass spectrometry, MHC class I peptide ligands are typically isolated by MHC immunoaffinity chromatography (MHC-IAC) and less often by mild acid elution (MAE). MAE may provide a cheap alternative to MHC-IAC for suspension cells but has been hampered by the high number of contaminating, MHC-unrelated peptides. Here, we optimized MAE, yielding MHC peptide ligand purities of more than 80%. When compared with MHC-IAC, obtained peptides were similar in numbers, identities, and to a large extent intensities, while the percentage of cysteinylated peptides was 5 times higher in MAE. The latter benefitted the discovery of MHC-allotype-specific, distinct cysteinylation frequencies at individual positions of MHC peptide ligands. MAE revealed many MHC ligands with unmodified, N-terminal cysteine residues which get lost in MHC-IAC workflows. The results support the idea that MAE might be particularly valuable for the high-confidence analysis of post-translational modifications by avoiding the exposure of the investigated peptides to enzymes and reactive molecules in the cell lysate. Our improved and carefully documented MAE workflow represents a high-quality, cost-effective alternative to MHC-IAC for suspension cells.The development of efficient artificial leaves relies on the subtle combination of molecular assemblies able to absorb sunlight, converting light energy into electrochemical potential energy and finally transducing it into accessible chemical energy. The electronic design of these charge transfer molecular machines is crucial to build a complex supramolecular architecture for the light energy conversion. Here, we present an ab initio simulation of the whole decay pathways of a recently proposed artificial molecular reaction center. A complete structural and energetic characterization has been carried out with methods based on density functional theory, its time-dependent version, and a broken-symmetry approach. On the basis of our findings we provide a revision of the pathway only indirectly postulated from an experimental point of view, along with unprecedented and significant insights on the electronic and nuclear structure of intramolecular charge-separated states, which are fundamental for the application of this molecular assembly in photoelectrochemical cells. Corticosterone order Importantly, we unravel the molecular driving forces of the various charge transfer steps, in particular those leading to the proton-coupled electron transfer final product, highlighting key elements for the future design strategies of such molecular assays.Surface patterning in the micro- and nanometer-range by means of pulsed laser interference has repeatedly proven to be a versatile tool for surface functionalization. With these techniques, however, the surface is often changed not only in terms of morphology but also in terms of surface chemistry. In this study, we present an in-depth investigation of the chemical surface modification occurring during surface patterning of copper by ultrashort pulsed direct laser interference patterning (USP-DLIP). A multimethod approach of parallel analysis using visualizing, topography-sensitive, and spectroscopic techniques allowed a detailed quantification of surface morphology as well as composition and distribution of surface chemistry related to both processing and atmospheric aging. The investigations revealed a heterogeneous surface composition separated in peak and valley regions predominantly consisting of Cu2O, as well as superficial agglomerations of CuO and carbon species. The evaluation was supported by a modeling approach for the quantification of XPS results in relation to heterogeneous surface composition, which was observed by means of a combination of different spectroscopic techniques.