Organic Substructures Research Articles

Students Constructing for Themselves the Concept of Chemical Shift Correlation for Organic Substructures

Students Constructing for Themselves the Concept of Chemical Shift Correlation for Organic Substructures

Imaging of Gαq Proteins in Mouse and Human Organs and Tissues.

G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by activating intracellular heterotrimeric G proteins. Several studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g., asthma and cancer. Recently, we developed specific radiotracers, [³H]PSB-15900-FR and [³H]PSB-16254-YM, for the Gαq family of G proteins by tritiation of the macrocyclic natural products FR900359 (FR) and YM-254890 (YM). In the present study, we utilized these potent radioligands to perform autoradiography studies in tissues of healthy mice, mouse models of disease, and human tissues. Specific binding was high, while non-specific binding was extraordinarily low, giving nearly identical results for both radioligands. High expression levels of Gαq proteins were detected in healthy mouse organs showing the following rank order of potency: kidney > liver > brain > pancreas > lung > spleen, while expression in the heart was low. Organ sub-structures, e.g., of mouse brain and lung, were clearly distinguishable. Whereas an acute asthma model in mice did not result in altered Gαq protein expressions as compared to control animals, a cutaneous melanoma model displayed significantly increased expression in comparison to healthy skin. These results suggest the future development of Gαq-protein-binding radio-tracers as novel diagnostics.

Molecular and Supramolecular Structure of a New Luminescent Hybrid Compound: (C5N2H14)2[BiBr6]Br·H2O

The reaction of homopiperazine, C5N2H12, with BiBr3 in strong hydrobromic acid affords a new organic-inorganic hybrid (C5N2H14)2[BiBr6]Br·H2O. It crystallizes in the orthorhombic space group, Pbca, with unit cell dimensions of a = 15.0775 (2), b = 15.7569 (2), and c = 20.7881 (4) Å, and eight formula units per unit cell. The crystal structure features slightly distorted octahedral BiBr63− and monoatomic Br− anions in the inorganic substructure and C5N2H142+ dications and adjacent water molecules in the organic substructure. Various weak interactions that include (N)H···Br, (N)H···O, and (O)H···Br hydrogen bonds ensure the assembling of the structural moieties into a 3D supramolecular structure. (C5N2H14)2[BiBr6]Br·H2O shows two emission bands in the photoluminescence spectrum, a rather narrow deep-blue PL at 432 nm, and a broadband red PL centered at 650 nm. Their nature and relations to the crystal structure are discussed in this paper.

Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines.

Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). At present, very little is known about GalNAc-Tyr prevalence, function, or biosynthesis. Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations.

Additively manufactured, solid object structures for adjustable image contrast in Magnetic Resonance Imaging

The choice of materials challenges the development of Magnetic Resonance Imaging (MRI) phantoms and, to date, is mainly limited to water-filled compartments or gel-based components. Recently, solid materials have been introduced through additive manufacturing (AM) to mimic complex geometrical structures. Nonetheless, no such manufactured solid materials are available with controllable MRI contrast to mimic organ substructures or lesion heterogeneities. Here, we present a novel AM design that allows MRI contrast manipulation by varying the partial volume contribution to a ROI/voxel of MRI-visible material within an imaging object. Two sets of 11 cubes and three replicates of a spherical tumour model were designed and printed using AM. Most samples presented varying MRI-contrast in standard MRI sequences, based mainly on spin density and partial volume signal variation. A smooth and continuous MRI-contrast gradient could be generated in a single-compartment tumour model. This concept supports the development of more complex MRI phantoms that mimic the appearance of heterogeneous tumour tissues.

Mound 28 from the Paulje necropolis in Brezjak. A contribution to the absolute chronology of the Late Bronze Age in Serbia

The paper brings the results of archaeological excavations of Mound 28 at the Paulje necropolis, conducted in the autumn of 2019, along with the excavations of two adjacent mounds. All of the aforementioned mounds were partially damaged and eroded through decades of ploughing. Consequently, remains of a Late Bronze Age burial were recorded solely in Mound 28. According to the grave inventory comprised of bronze jewellery and analogies from concurrent necropolises, it is assumed that the burial belongs to a female individual (?). Besides the extraordinary examples of bronze jewellery, such as pins, an arm ring, bracelets, crescent-shaped pendants, torques, and remains of amber jewellery, the organic substructure below the fully cast arm ring has been successfully dated. According to the absolute dating, the jewellery is attributed to the 14th century BC, and the inventory of the grave completely corresponds to the previously dated features from the Paulje necropolis. Therefore, certain forms of bronze jewellery were provided with a more precise chronological position based on the absolute dates. The burial is attributed to the Brezjak culture.

Prevention and treatment of radiotherapy-induced side effects.

Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients’ quality of life and to escalate radiation doses to tumors when necessary. High‐precision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ‐specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery.

Three-Dimensional Perovskite Methylhydrazinium Lead Chloride with Two Polar Phases and Unusual Second-Harmonic Generation Bistability above Room Temperature

Formation of noncentrosymmetric three-dimensional (3D) lead halide perovskites has been a widely sought after goal because the polar structure opens up new vistas to properties of these materials, e.g., improved charge separation for photovoltaics arising from ferroelectric order. Here, we report growth and unique properties of a new highly distorted 3D perovskite, methylhydrazinium lead chloride (CH3NH2NH2PbCl3, MHyPbCl3). This perovskite crystallizes in polar P21 structure at room temperature, which consists of two types of PbCl6 octahedra: one weakly and another strongly deformed. The unusual deformation of every second perovskite layer is forced by the large size of methylhydrazinium cations and the ability of NH2+ terminal groups of methylhydrazinium cations to form coordination bonds with Pb2+ metal centers. On heating, MHyPbCl3 undergoes a phase transition at 342 K into another polar Pb21m phase with ordered organic cations. Temperature-resolved second-harmonic generation (TR-SHG) measurements confirm acentricity of both phases and show that second-harmonic response is enhanced for the high-temperature Pb21m phase. This intriguing property of MHyPbCl3 has been employed to demonstrate an unprecedented kind of quadratic nonlinear optical switching in which a second-harmonic response is switched between a room-temperature, low-SHG state and a high-temperature, high-SHG state. X-ray diffraction shows that enhancement of polar properties is due to rearrangement of the perovskite’s organic substructure. There is a clear pyrocurrent peak, but switching of the electric polarization could not be observed. Optical studies showed that MHyPbCl3 is a wide-bandgap material with a bandgap of 3.4 eV (365 nm). At low temperatures, it exhibits weak UV emissions at 362 and 369 nm as well as a strong broadband white emission.

What You See Is Not What You Get: On the Accuracy of Voxel-Based Dosimetry in Molecular Radiotherapy.

Improvements in quantitative SPECT/CT have aroused growing interest in voxel-based dosimetry for radionuclide therapies, because it promises visualization of absorbed doses at a voxel level. In this work, SPECT/CT-based voxel-level dosimetry of a 3-dimensional (3D) printed 2-compartment kidney phantom was performed, and the resulting absorbed dose distributions were examined. Additionally, the potential of the PETPVC partial-volume correction tool was investigated. Methods: Both kidney compartments (70% cortex, 30% medulla) were filled with different activity concentrations, and SPECT/CT imaging was performed. The images were reconstructed using varying settings (iterations, subsets, and postfiltering). On the basis of these activity concentration maps, absorbed dose distributions were calculated with precalculated 177Lu voxel S values and an empiric kidney half-life. An additional set of absorbed doses was calculated after applying PETPVC for partial-volume correction of the SPECT reconstructions. Results: SPECT/CT imaging blurs the 2 discrete suborgan absorbed dose values into a continuous distribution. Although this effect is slightly improved by applying more iterations, it is enhanced by additional postfiltering. By applying PETPVC, the absorbed dose values are separated into 2 peaks. Although this leads to a better agreement between SPECT/CT-based and nominal values, considerable discrepancies remain. In contrast to the calculated nominal absorbed doses of 7.8 and 1.6 Gy (in the cortex and medulla, respectively), SPECT/CT-based voxel-level dosimetry resulted in mean absorbed doses of 3.0-6.6 Gy (cortex) and 2.7-5.1 Gy (medulla). PETPVC led to improved ranges of 6.1-8.9 Gy (cortex) and 2.1-5.4 Gy (medulla). Conclusion: Our study showed that 177Lu quantitative SPECT/CT imaging leads to voxel-based dose distributions largely differing from the real organ distribution. SPECT/CT imaging and reconstruction deficiencies might directly translate into unrealistic absorbed dose distributions, thus questioning the reliability of SPECT-based voxel-level dosimetry. Therefore, SPECT/CT reconstructions should be adapted to ensure an accurate quantification of the underlying activity and, therefore, absorbed dose in a volume of interest of the expected object size (e.g., organs, organ substructures, lesions, or voxels). As an example, PETPVC largely improves the match between SPECT/CT-based and nominal dose distributions. In conclusion, the concept of voxel-based dosimetry should be treated with caution. Specifically, one should remember that the absorbed dose distribution is mainly a convolved version of the underlying SPECT reconstruction.

Transition metal complexes with fractionally charged TCNQ radical anions as structural templates for multifunctional molecular conductors

Structures that combine transition metal complexes with fractionally charged organic cations or anions are of interest as potential multifunctional materials, in which conducting behavior of the organic substructure is supplemented by other properties, provided by the transition metal component. Here we review such hybrid structures prepared with ligand-capped transition metal cations and radical anions derived from the organic acceptor 7,7,8,8-tetracyanoquinodimethane (TCNQ) or its analogs. Our analysis of the Cambridge Structural Database has revealed 520 structures of this type, among which only 35 contain fractionally charged organic anions. The requirement of fractional charge on the organic anion is paramount for achieving high electrical conductivity. After introducing a few basic concepts, we provide classification of such structures and a detailed summary of their properties.

C3a/C3aR axis confers the protection against urinary tract infection

Development of biomimetic and instructive materials is emerging as a promising approach for redirecting fibrotic wound healing into a regenerative process. In nature, complete tissue regeneration can transpire in certain organ substructures, during embryogenesis and, remarkably, in some organisms in which whole limbs can regrow. These regenerative phenomena were observed to possess specific extracellular matrices, as well as stem cell niches and regulatory signaling pathways, that likely act as spatiotemporal organizers of these preferred outcomes. Biomimetic materials are now improving on the limitations of existing wound care treatments because they are being designed to stimulate these spatiotemporal cues, thus supporting regeneration within host tissues. A variety of novel materials have already emerged and demonstrated promise both in preclinical studies and in patients. This review discusses the recent advances in understanding these biomimetic and instructive properties and their integration into wound care scaffolds.

ChemInform Abstract: Diastereoselective Synthesis of Vicinally Bis(trifluoromethylated) Alkylboron Compounds Through Successive Insertions of 2,2,2‐Trifluorodiazoethane.

The usefulness of embedded CF3 substituents within organic substructures necessitates the development of diverse methods for incorporating this functional group. A recently reported route to α-trifluoromethylated alkylboron compounds by an α-transfer mechanism has now been extended to the synthesis of unprecedented, vicinally ditrifluoromethylated alkylboron compounds in a diastereoselective fashion. The utility of these products is highlighted by conversion of the C-B bond into other functional groups.

Diastereoselective synthesis of vicinally bis(trifluoromethylated) alkylboron compounds through successive insertions of 2,2,2-trifluorodiazoethane.

The usefulness of embedded CF3 substituents within organic substructures necessitates the development of diverse methods for incorporating this functional group. A recently reported route to α-trifluoromethylated alkylboron compounds by an α-transfer mechanism has now been extended to the synthesis of unprecedented, vicinally ditrifluoromethylated alkylboron compounds in a diastereoselective fashion. The utility of these products is highlighted by conversion of the C-B bond into other functional groups.

Diastereoselective Synthesis of Vicinally Bis(trifluoromethylated) Alkylboron Compounds through Successive Insertions of 2,2,2‐Trifluorodiazoethane

AbstractThe usefulness of embedded CF3 substituents within organic substructures necessitates the development of diverse methods for incorporating this functional group. A recently reported route to α‐trifluoromethylated alkylboron compounds by an α‐transfer mechanism has now been extended to the synthesis of unprecedented, vicinally ditrifluoromethylated alkylboron compounds in a diastereoselective fashion. The utility of these products is highlighted by conversion of the CB bond into other functional groups.

Primary- and secondary-octahedral distortion factors in bis(1,4-H2-1,2,4-triazolium) pentabromidoantimonate(III)–1,4-H2-1,2,4-triazolium bromide

The analysis of octahedral distortion in the structure of inorganic–organic (C2H4N3)2[SbBr5]·(C2H4N3)Br (BTPTB) bromidoantimonate(III) determined at 295 and 85K, supported by the Hirshfeld surface analysis and the data retrieved from the Cambridge Structural Database, is presented. The anionic substructure of BTPTB is built from distorted [SbBr6]3− octahedra that are connected by the cis corners forming polymeric one-dimensional [{SbBr5}n]2n− zig-zag chains running parallel to the a axis and isolated Br− ions. The organic substructure consists of the fully ordered 1,4-H2-1,2,4-triazolium cations. The oppositely charged substructures are linked by the system of N(C)–H⋯Br hydrogen bonds causing further distortion of [SbBr6]3− octahedra. The comparison of octahedral geometry and distortions found in the structure of BTPTB determined at room and low temperature, to access the attractive nature of hydrogen bonds, clearly shows that hydrogen bond interactions are responsible for secondary distortion of octahedra and the observed deviations are comparable to primary distortion that is caused by the intrinsic interactions within inorganic substructure. Furthermore, a comparison of packing features and interactions in BTPTB with those in the structure of organic 1,4-H2-1,2,4-triazolium bromide, (C2H4N3)Br (TB), also determined at 295 and 85K, confirms the importance and hierarchy of factors that are responsible for polyhedral distortion.

Copper-Mediated Radical Trifluoromethylation of Unsaturated Potassium Organotrifluoroborates

Copper-mediated trifluoromethylation of unsaturated organotrifluoroborates with the Langlois reagent (NaSO2CF3) and TBHP allows the introduction of trifluoromethyl groups into a variety of organic substructures. The reactions are easy to set up, the conditions are mild and general, and the process provides access to trifluoromethylated alkynes, alkenes, arenes, and heteroarenes in fair to good yields.

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

Organs are complex structures that consist of multiple tissues with different levels of gene expression. To achieve comprehensive coverage and accurate quantitation data, organs ideally should be separated into morphologic and/or functional substructures before gene or protein expression analysis. However, because of complex morphology and elaborate isolation protocols, to date this often has been difficult to achieve. Kidneys are organs in which functional and morphologic subdivision is especially important. Each subunit of the kidney, the nephron, consists of more than 10 subsegments with distinct morphologic and functional characteristics. For a full understanding of kidney physiology, global gene and protein expression analyses have to be performed at the level of the nephron subsegments; however, such studies have been extremely rare to date. Here we describe the latest approaches in quantitative high-accuracy mass spectrometry-based proteomics and their application to quantitative proteomics studies of the whole kidney and nephron subsegments, both in human beings and in animal models. We compare these studies with similar studies performed on other organ substructures. We argue that the newest technologies used for preparation, processing, and measurement of small amounts of starting material are finally enabling global and subsegment-specific quantitative measurement of protein levels in the kidney and other organs. These new technologies and approaches are making a decisive impact on our understanding of the (patho)physiological processes at the molecular level.

Supramolecular templates for the synthesis of new nanostructured uranyl compounds: Crystal structure of [NH3(CH2)9NH3][(UO2)(SeO4)(SeO2OH)](NO3)

Crystals of a new uranyl selenate, [NH3(CH2)9NH3][(UO2)(SeO4)(SeO2OH)](NO3) (1), were prepared by isothermal evaporation from aqueous solution at room temperature. The crystal structure was solved by the direct method $$ P\bar 1 $$ , a = 10.7480(7), b = 13.8847(9), c = 14.6363(10) A, α = 109.9600(10)°, β = 103.212(2)°, γ = 90.4090(10)°, V = 1990.0(2) A3, Z= 4) and refined to R 1 = 0.0379 (wR 2 = 0.0636) for 8515 reflections with ¦Fo¦ ≥ 4σF. The structure is based on [(UO2)(SeO4)(SeO2OH)]-layers parallel to the (001) plane. In the structure of 1, there are two crystallographically independent 1,9-diammoniononane cations forming micelles in which the hydrocarbon chains are packed crosswise. The micelles are cylinders with an elliptical cross section and a rough surface. They are organized by the principle of hydrophilic and hydrophobic interactions. The cylinders are separated from each other by layers of triangular NO 3 − groups. Compound 1 is an example of organic-inorganic composites with a unidimensional organic substructure in which the protonated chain-like diamine molecules arranged crosswise form cylindrical supramolecular templates.

Scope of the Suzuki−Miyaura Cross-Coupling Reactions of Potassium Heteroaryltrifluoroborates

A wide variety of bench-stable potassium heteroaryltrifluoroborates were prepared, and general reaction conditions were developed for their cross-coupling to aryl and heteroaryl halides. The cross-coupled products were obtained in good to excellent yields. This method represents an efficient and facile installation of heterocyclic building blocks onto preexisting organic substructures.

ROCK-mediated contractility, tight junctions and channels contribute to the conversion of a preapical patch into apical surface during isochoric lumen initiation

Epithelial cells assemble into three-dimensional aggregates to generate lumen-containing organ substructures. Cells therein contact the extracellular matrix with their basal surface, neighbouring cells with their contact surface and the lumen with their apical surface. We investigated the development of single MDCK cells into aggregates with lumen using quantitative live-cell imaging to identify morphogenetic rules for lumen formation. In two-cell aggregates, membrane insertion into the contact surface established a preapical patch (PAP) characterized by the presence of the apical marker gp135, microvilli and the absence of E-cadherin. This PAP originated from a compartment that had hallmarks of an apical recycling endosome, and matured through Brefeldin-A-sensitive membrane trafficking and the establishment of tight junctions around itself. As a result of the activity of water and ion channels, an optically resolvable lumen formed. Initially, this lumen enlarged without changes in aggregate volume or cell number but with decreasing cell volumes. Additionally, the ROCK1/2-myosin-II pathway counteracted PAP and lumen formation. Thus, lumen formation results from PAP establishment, PAP maturation, lumen initiation and lumen enlargement. These phases correlate with distinct cell surface and volume patterns, which suggests that such morphometric parameters are regulated by trafficking, ROCK-mediated contractility and hydrostatic pressure or vice versa.