Competing Supramolecular Forces: Boron Coordination vs π-π Stacking

This study explores the impact of fluorination levels in azopyridine Lewis bases on their ability to direct the formation of B←N coordination adducts or cocrystals with phenylboronic ester. We hypothesize that the degree of fluorination can be used as a tool to control the outcome of supramolecular bonding competition, thus influencing complex self-assembly. A series of azopyridines with varying degrees of fluorination were synthesized and reacted with phenylboronic ester. Their structures were analyzed using Hartree-Fock calculations, Hirshfeld surface analyses, and single crystal X-ray diffraction to assess the impact of fluorination on supramolecular interactions. The study reveals that azopyridines with up to two fluorine atoms form B←N coordination complexes, while perfluorinated azopyridine leads to cocrystal formation through π-stacking interactions. The outcome depends on the electronic properties of the pyridyl nitrogens, influenced by the level of fluorination. Fluorination in azopyridine Lewis bases serves as an effective strategy to modulate supramolecular bonding competition between boron coordination and π-stacking. This approach enables the selective formation of desired supramolecular structures, highlighting the utility of fluorination in guiding the self-assembly process. The findings have implications for the development of functional materials and 2D devices, offering a novel method for controlling the architecture of supramolecular assemblies

miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer

This work is licensed under a Creative Commons Attribution 4.0 International License.Elevated prostaglandin E2 (PGE2) levels are observed in colorectal cancer (CRC) patients, and this increase is associated with poor prognosis. Increased synthesis of PGE2 in CRC has been shown to occur through COX-2-dependent mechanisms; however, loss of the PGE2-catabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, HPGD), in colonic tumors contributes to increased prostaglandin levels and poor patient survival. While loss of 15-PGDH can occur through transcriptional mechanisms, we demonstrate that 15-PGDH can be additionally regulated by a miRNA-mediated mechanism. We show that 15-PGDH and miR-21 are inversely correlated in CRC patients, with increased miR-21 levels associating with low 15-PGDH expression. 15-PGDH can be directly regulated by miR-21 through distinct sites in its 3′ untranslated region (3′UTR), and miR-21 expression in CRC cells attenuates 15-PGDH and promotes increased PGE2 levels. Additionally, epithelial growth factor (EGF) signaling suppresses 15-PGDH expression while simultaneously enhancing miR-21 levels. miR-21 inhibition represses CRC cell proliferation, which is enhanced with EGF receptor (EGFR) inhibition. These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE2.NIH R01 CA134609NIH R01 AR069044NIH/NCI Cancer Center Support Grant (P30 CA168524)New Jersey Commission on Cancer ResearchAmerican Heart Association (15GRNT23240019

Engineering Lipophilic Aggregation of Adapalene and Adamantane-Based Cocrystals via van der Waals Forces and Hydrogen Bonding

Lipophilic aggregation using adamantanes is a widely exploited molecular property in medicinal and materials chemistry. Adamantanes are traditionally installed to molecular units via covalent bonds. However, the noncovalent installation of adamantanes has been relatively underexplored and presents the potential to bring properties associated with adamantanes to molecules without affecting their intrinsic properties (e.g., pharmacophores). Here, we systematically study a series of adamantanecarboxylic acids with varying substitution levels of methyl groups and their cocrystals with bipyridines. Specifically, single-crystal X-ray diffraction shows that while the directionality of single-component adamantanes is notably sensitive to changes in methyl substitution, hydrogen-bonded cocrystals with bipyridines show consistent and robust packing due to π-stacking predominance. Our observations are supported by Hirshfeld surface and energy framework analyses. The applicability of cocrystal formation of adamantanes bearing carboxylic acids was used to generate the first cocrystals of adapalene, an adamantane-bearing retinoid used for treating acne vulgaris. We envisage our study to inspire noncovalent (i.e., cocrystal) installation of adamantanes to generate lipophilic aggregation in multicomponent systems

Confinement and Separation of Benzene from an Azeotropic Mixture Using a Chlorinated B←N Adduct

Separations of azeotropic mixtures are typically carried out using energy-demanding processes (e.g., distillation). Here, we report the capacity of a self-assembled chlorinated boronic ester-based adduct to confine acetonitrile and benzene in channels upon crystallization. The solvent confinement occurs via a combination of hydrogen bonding and [π···π] interactions. Quantitative separation of benzene from an azeotropic 1:1 mixture of a benzene/acetonitrile (v/v), and methanol is achieved through crystallization with the chlorinated adduct by complementary [C–H···O] and [C–H···π] interactions. Inclusion behavior is rationalized by molecular modeling and crystallographic analysis. The chlorinated boronic ester adduct shows the potential of modularity via isosteric substitution for the separation of challenging chemical mixtures (e.g., azeotropes)

Deep JHKs and Spitzer Imaging of Four Isolated Molecular Cloud Cores

We present observations in eight wavebands from 1.25-24 microns of four dense cores: L204C-2, L1152, L1155C-2, and L1228. Our goals are to study the YSO population of these cores and to measure the mid-infrared extinction law. With our combined near-infrared and Spitzer photometry, we classify each source in the cores as, among other things, background stars, galaxies, or embedded young stellar objects (YSOs). L1152 contains three YSOs and L1228 has seven, but neither L204C-2 nor L1155C-2 appear to contain any YSOs. We estimate an upper limit of 7x10^-5 to 5x10^-4 solar luminosities for any undiscovered YSOs in our cores. We also compute the line-of-sight extinction law towards each background star. These measurements are averaged spatially, to create chi-squared maps of the changes in the mid-infrared extinction law throughout our cores, and also in different ranges of extinction. From the chi-squared maps we identify two small regions in L1152 and L1228 where the outflows in those cores appear to be destroying the larger dust grains, thus altering the extinction law in those regions. On average, however, our extinction law is relatively flat from 3.6 to 24 microns for all ranges of extinction and in all four cores. From 3.6 to 8 microns this law is consistent with a dust model that includes larger dust grains than the diffuse interstellar medium, which suggests grain growth has occurred in our cores. At 24 microns, our extinction law is 2-4 times higher than predicted by dust models. However, it is similar to other empirical measurements.Comment: Accepted by ApJ. 46 pages, 20 figures, 6 tables in preprint format. For a version with full-resolution figures, see http://peggysue.as.utexas.edu/SIRTF/PAPERS

Mechanistic insights into the C₅₅-P targeting lipopeptide antibiotics revealed by structure-activity studies and high-resolution crystal structures

The continued rise of antibiotic resistance is a global concern that threatens to undermine many aspects of modern medical practice. Key to addressing this threat is the discovery and development of new antibiotics that operate by unexploited modes of action. The so-called calcium-dependent lipopeptide antibiotics (CDAs) are an important emerging class of natural products that provides a source of new antibiotic agents rich in structural and mechanistic diversity. Notable in this regard is the subset of CDAs comprising the laspartomycins and amphomycins/friulimicins that specifically target the bacterial cell wall precursor undecaprenyl phosphate (C(55)-P). In this study we describe the design and synthesis of new C(55)-P-targeting CDAs with structural features drawn from both the laspartomycin and amphomycin/friulimicin classes. Assessment of these lipopeptides revealed previously unknown and surprisingly subtle structural features that are required for antibacterial activity. High-resolution crystal structures further indicate that the amphomycin/friulimicin-like lipopeptides adopt a unique crystal packing that governs their interaction with C(55)-P and provides an explanation for their antibacterial effect. In addition, live-cell microscopy studies provide further insights into the biological activity of the C(55)-P targeting CDAs highlighting their unique mechanism of action relative to the clinically used CDA daptomycin

Upper limits for undetected trace species in the stratosphere of Titan

In this paper we describe a first quantitative search for several molecules in Titan's stratosphere in Cassini CIRS infrared spectra. These are: ammonia (NH3), methanol (CH3OH), formaldehyde (H2CO), and acetonitrile (CH3CN), all of which are predicted by photochemical models but only the last of which observed, and not in the infrared. We find non-detections in all cases, but derive upper limits on the abundances from low-noise observations at 25{\deg}S and 75{\deg}N. Comparing these constraints to model predictions, we conclude that CIRS is highly unlikely to see NH3 or CH3OH emissions. However, CH3CN and H2CO are closer to CIRS detectability, and we suggest ways in which the sensitivity threshold may be lowered towards this goal.Comment: 11 pages plus 6 figure file

ACR Appropriateness Criteria® Spinal Bone Metastases

The spine is a common site of involvement in patients with bone metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive tumor can result in neurologic deterioration caused by spinal cord compression or cauda equina involvement. The treatment of spinal bone metastases depends on histology, site of disease, extent of epidural disease, extent of metastases elsewhere, and neurologic status. Treatment recommendations must weigh the risk-benefit profile of external beam radiation therapy (EBRT) for the particular individual's circumstance, including neurologic status, performance status, extent of spinal disease, stability of the spine, extra-spinal disease status, and life expectancy. Patients with spinal instability should be evaluated for surgical intervention. Research studies are needed that evaluate the combination or sequencing of localized therapies with systemic therapies including chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in the management of spinal oligometastasis, radioresistant spinal metastasis, and previously irradiated but progressive spinal metastasis are emerging, but more research is needed to validate the findings from retrospective studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140115/1/jpm.2012.0376.pd

Benchtop flow-NMR for rapid online monitoring of RAFT and free radical polymerisation in batch and continuous reactors

A “Benchtop” NMR spectrometer is used for detailed monitoring of controlled and free radical polymerisations performed in batch and continuous reactors both offline and in real-time. This allows detailed kinetic analysis with unprecedented temporal resolution for reactions which reach near completion in under five minutes