Terminal Position Research Articles

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

In this study, novel fluorinated carboxylic acid esters of the generic structure TfO–CH2–(CF2)n–COOCH3 (n = 2,4,6, Tf = triflate) were synthesized. The triflates were reacted with 2-hydroxy-3,4,5-trimethoxybenzaldehyde via Williamson ether syntheses. The resulting electron-rich compounds were used as aldehydes in the Rothemund reaction with pyrrole to form ester-substituted porphyrins. After metalation with Ni(acac)2 and hydrolysis electron-rich porphyrins were obtained, that are equipped with covalently attached long chain acid substituents. The target compounds have potential applications in catalysis, sensing, and materials science. The fluorinated aliphatic carboxylic acids (TfO–CH2–(CF2)n–COOCH3) with triflate as leaving group in terminal position are easily accessible and versatile building blocks for attaching long chain acids (pKa 0–1) to substrates in Williamson ether-type reactions.

TMIC-30. FOREBRAIN TO HINDBRAIN INVASION IN GLIOBLASTOMA IS DIRECTED BY ANATOMICALLY DISTINCT REACTIVE ASTROCYTES

Abstract Initial detection of glioblastoma (GBM) often reveals a large mass in the forebrain; however, the hazard for many patients lies in extensive invasion that can extend far from the primary tumor. New evidence suggests that end-stage GBM coincides with malignant infiltration of the pons and brainstem. Mechanisms that direct tumor cells from initial positions within the forebrain to terminal positions in the brainstem are largely unknown. Our analysis indicates that spatially defined, reactive astrocytes instruct GBM cells to either proliferate or invade. During development, astrocytes help establish directional gradients and boundaries that mediate proper routing of migrating neural cells and extending axons. We posit that onco-reactive astrocytes re-engage these guidance programs to direct tumor cells to the brainstem. To test this hypothesis, we exposed a series of human GBM models to media conditioned by cortical, midbrain, or brainstem reactive astrocytes. When treated with cortical conditioned media, tumor cells were driven into a state of hyper-proliferation, which mirrored early-stage forebrain tumor generation. In contrast, midbrain and brainstem conditioned medias suppressed proliferation and enhanced the rate of tumor cell migration. RNA sequencing corroborated these functional data, identifying cell division programs augmented in GBM cells exposed to cortical astrocyte conditioned media. This contrasted with axon development and guidance programs enriched in GBM cells exposed to midbrain and especially brainstem conditioned medias. Finally, mRNA and protein analysis identified region-specific engagement with the Eph-ephrin guidance system patterned along a forebrain to hindbrain trajectory. These data support a new hypothesis that GBM tumors recapitulate a form of neurodevelopment, invading specific anatomic regions based on cues generated by resident reactive astrocytes.

Hydrogen bond, protonation, and coordination-induced supramolecular chirality inversion in glutamide-based amphiphilic self-assembly

In this study, we have synthesized two types of Y-shaped chiral amphiphiles, namely L-BG and L-PG, with a benzene or pyridine ring at the terminal position, respectively. The optimized conformations of both amphiphiles indicate the presence of intramolecular interactions. In dimethylformamide (DMF) solution at the monomeric state, both amphiphiles exhibit positive cotton effects; however, in DMF/H2O mixed solution, the cotton effects are inverted. Molecular dynamics simulations reveal that both intermolecular and intramolecular hydrogen bonds facilitate the inversion of supramolecular chirality. Additionally, protonation and coordination of L-PG assembly results in chirality inversion and transformation of emission. This study emphasizes the significance of both inter- and intramolecular hydrogen bonds in the assembly process, providing insights into stimuli-responsive chiral supramolecular materials.

Microwave‐Assisted/Pd‐Catalyzed Regioselective Double C‐N Arylations of 1,2,3‐Triiodobenzene: Efficient and Unexpected Synthesis of N1,N2‐Bis(2,3‐diiodoaryl)benzene‐1,2‐diamines

ABSTRACTA simple, direct, and regioselective protocol to the synthesis of N1,N2‐bis(2,3‐diiodoaryl)benzene‐1,2‐diamines through highly regioselective microwave‐assisted/palladium‐catalyzed double C‐N arylations of 1,2,3‐triiodobenzene and benzene‐1,2‐diamine is reported. Remarkably, the C‐N arylations proceeded bimolecularly at the terminal positions, the most active and less hindered position. This process was efficient and tolerated a wide range of substrates. The reaction of electron‐rich/neutral 1,2,3‐triiodoarene systems and electron‐rich 1,2‐diamines under the optimized conditions provided the highest isolated yields. This article describes a method for the first and unprecedented synthesis of tetra‐iodinated N1,N2‐diarylbenzene‐1,2‐diamine and iodinated 5,10‐dihydrophenazine products that is regioselective and scalable and provides useful derivatives for other chemical reactions especially in the synthesis of new NHC ligands.

The Coordinated Changes in Platelet Glycan Patterns with Blood Serotonin and Exosomes

The structures of glycans, specifically their terminal positions, play an important role as ligands for receptors in regulating the adhesion ability of platelets. Recent advances in our understanding of free/unbound serotonin (5-HT) in blood plasma at supraphysiological levels implicate it as one of the most profound influencers in remodeling the platelet’s surface N-glycans. Proteomic analysis of the membrane vesicles identified enzymes, specifically glycosyltransferases, only on the surface of the platelets isolated from the supraphysiological level of 5-HT-containing blood plasma. However, these enzymes can only be effective on the cell surface under certain biological conditions, such as the level of their substrates, temperature, and pH of the environment. We hypothesize that exosomes released from various cells coordinate the required criteria for the enzymatic reaction on the platelet surface. The elevated plasma 5-HT level also accelerates the release of exosomes from various cells, as reported. This review summarizes the findings from a wide range of literature and proposes mechanisms to coordinate the exosomes and plasma 5-HT in remodeling the structures of N-glycans to make platelets more prone to aggregation.

Fiber Bragg Grating-based sensor for measuring supersonic inlet terminal shock at different angles of attack

This study presents a multipoint pressure measurement system using fiber Bragg grating sensors to detect terminal shock positions. The system consisted of a fiber optic string encapsulated with multiple diaphragm-based fiber Bragg grating sensors, capable of detecting flow field characteristics at fourteen different axial positions of the inlet. The calibration results indicated a sensitivity of 46.47 pm/kPa, a linear correlation coefficient of 0.9997, and a maximum repeatability error below 1.44%. In supersonic wind tunnel tests, the system effectively measured pressure and located the terminal shock across varying angles of attack and throttling degrees. The maximum difference compared to conventional pressure sensors was 4.7%, and the terminal shock positioning error was limited to 1.2%. Overall, the system has robust multipoint measurement capabilities and is priced at only one-tenth of traditional sensors, showing great potential in the field of inlet measurements.

Sequence-Defined Synthesis Enabled by Fast and Living Anionic Monoaddition of Vinyl Monomers.

The selective monoaddition of polymerizable vinyl monomers like styrenes and methacrylates in a living manner has been achieved for the flash-flow preparation of molecules in a defined sequence with high selectivity. We demonstrated the sequence-defined synthesis of multifunctional molecules using an initiator, functionalized styrenes, diarylethylenes, various methacrylates, and an electrophilic trapping reagent at the living terminus (six-component sequential connection at maximum) without any intermediate purification steps. The anionic living terminus of the vinyl monomers in the flow system described herein is active for polymerization, such that the styrene or methacrylate sequence can be expanded to afford highly dispersed oligomers without affecting other single units, which means that the unequivocal sequences were successfully inserted into the internal or terminal positions. The methodology described herein provides an adaptable method for the construction of new molecular spaces based on unimolecular sequence control and pinpoint functionalization.

Sequence‐Defined Synthesis Enabled by Fast and Living Anionic Monoaddition of Vinyl Monomers

The selective monoaddition of polymerizable vinyl monomers like styrenes and methacrylates in a living manner has been achieved for the flash‐flow preparation of molecules in a defined sequence with high selectivity. We demonstrated the sequence‐defined synthesis of multifunctional molecules using an initiator, functionalized styrenes, diarylethylenes, various methacrylates, and an electrophilic trapping reagent at the living terminus (six‐component sequential connection at maximum) without any intermediate purification steps. The anionic living terminus of the vinyl monomers in the flow system described herein is active for polymerization, such that the styrene or methacrylate sequence can be expanded to afford highly dispersed oligomers without affecting other single units, which means that the unequivocal sequences were successfully inserted into the internal or terminal positions. The methodology described herein provides an adaptable method for the construction of new molecular spaces based on unimolecular sequence control and pinpoint functionalization.

Cobalt-Catalyzed Divergence in C(sp3)-H Functionalization of 9H-Fluorene: A Streamlined Approach Utilizing Alcohols.

Sustainable chemical production demands the creation of innovative catalysts and catalytic technologies. While the development of coherent and robust catalytic systems using earth-abundant transition metals is essential, it remains a significant challenge. Herein, an expedient divergence strategy for tandem dehydrogenative C(sp3)-H alkylation and cyclization reactions of 9H-fluorene using a newly developed N,N-bidentate cobalt catalytic system is developed. This method capitalizes on the use of abundant and readily accessible alcohol. Demonstrating wide-ranging applicability, the catalytic protocol successfully integrated a diverse array of fluorenes and alcohols. This includes benzylic, heteroaromatic, and aliphatic primary and secondary alcohols, amassing a total of 75 distinct examples. When applied to sterically bulky alcohols, the reaction preferentially undergoes alkenylation, yielding a tetrasubstituted olefin as the main product. In the case of diols, the expected outcome is Dual-fluorescence at both terminal positions. This process leads to difluorination, followed by a cyclization step, culminating in the formation of a relatively unprecedented spiro compound. The scalability of this method has been validated through gram-scale synthesis. Control experiments have shed light on the reaction mechanism, indicating that it progresses through an unsaturated intermediate and adheres to the borrowing hydrogen pathway.

Establishing Composition of Solid Solution Based on Single Crystal and Powder X-ray Measurement: The Case of Halogenated Bismuth(III) Complexes with Acetophenone-4-methyl-3-thiosemicarbazone

New bismuth (III) complexes with acetophenone-4-methyl-3-thiosemicarbazone (L) and halogens (Cl and Br) in both bridging and terminal positions have been synthesized and structurally characterized using single-crystal X-ray diffraction. The pure complexes (Cl or Br) were found to be highly isostructural, which motivated our attempts to create solid solutions of these complexes. A series of such compounds was prepared using various procedures and stoichiometries. A method for determining the mutual concentrations of different halogens, based on the positions of selected peaks in powder diffraction patterns, was tested and compared with other methods.

Unsupervised identification of zone-level anomalies in VAV terminal units utilizing autoencoders and PCA

The effective operation of HVAC systems is crucial to minimize energy inefficiencies and occupant discomfort. However, these systems can experience various problems, including hardware and software-related anomalies. In contrast to most existing fault detection and diagnostic approaches, which rely on simple rules and alarms, this study introduces novel unsupervised approaches for detecting zone anomalies in variable air volume (VAV) air handling units (AHUs). The methods utilize autoencoders (AE) and principal component analysis (PCA). To evaluate the effectiveness of the proposed methods, both a synthetic dataset and measured data from a 28-zone VAV AHU system were investigated. The proposed method successfully detected several zone temperature and airflow anomalies using the AE-based method, and several zone anomalies were also identified using the PCA-AE approach by considering four commonly available zone-level trend logs in VAV AHUs namely temperature, airflow, airflow set-point, and VAV terminal damper position. The findings demonstrated the great adaptability of the proposed methods in detecting a wide range of zone anomalies in any modern building equipped with VAV AHUs, giving operators valuable insights about the system and notifying them of potential faults at an early stage.

Deciphering origins of hydrocarbon deposits by means of intramolecular carbon isotopes of propane adsorbed on sediments

Hydrocarbons are one of the important fluids within the Earth’s crust, and different biotic and abitoic processes can generate hydrocarbon during geological periods. Tracing the sources and sinks of hydrocarbons can help us better understand the carbon cycle of the earth. In this study, an improved approach of adsorbed hydrocarbons extraction from sediments was established. The improved thermal desorption approach, compound-specific isotope analysis and position-specific isotope analysis were integrated to investigate the molecular and intramolecular isotope fractionation between trace hydrocarbon gases within sediments and geological hydrocarbon deposits. The isotopic compositions of the terminal position carbon of propane (δ13Cterminal) serves as a correlation indicator between trace hydrocarbon gases within sediments and geological hydrocarbon deposits. The tight sandstone gas from the Turpan-Hami Basin is a first case study for the application of this novel method to trace hydrocarbon origins. The results showed that the hydrocarbons in the tight sandstone gases in the study area most likely originated from humic organic matter (type III kerogen) at an early mature stage. δ13Cterminal values of the thermally desorbed propane gases from different source rocks were distinguishable and the values of the tight sandstone gases significantly overlap with those of the Lower Jurassic Sangonghe source rocks, suggesting their genetic relationship. Overall, the results provided novel position-specific carbon isotopic constraints on origins of hydrocarbons.

Androdioecy in Ranunculus ficaria ssp. ficaria (Ranunculaceae)

Androdioecy was for the first time studied in detail in the fibrous-rooted herbaceous ephemeroid polycarpic plant Ranunculus ficaria ssp. ficaria in the Moscow Region during 2019–2023. It has been established that this subspecies produces two types of flowers: perfect and staminate (remains of carpels with reduced non-functioning stigmas are preserved). Perfect flowers and their component parts are always larger than those of staminate flowers. Populations consist of three types of individuals: with perfect flowers exclusively, with perfect and staminate flowers, and with staminate flowers only. Synflorescence of R. ficaria ssp. ficaria is a closed thyrsus, the subunits of which are dichasia. In andromonoecious plants, perfect flowers are located on the top of the thyrsus axis and take a terminal position in paracladial dichasia, while staminate flowers are formed exclusively on the lateral axes of dichasia. In the five studied populations, plants with perfect flowers predominate (from 86.3 to 93.7%). Over a five-year observation period, individuals of different sexual forms did not change the sex of flowers, and the sex ratio in populations remained stable without sharp fluctuations.

Peptide retention time prediction for hydrophilic interaction liquid chromatography at acidic pH in formic-acid based eluents

Peptide separation selectivity was evaluated for hydrophilic interaction liquid chromatography (HILIC) ZIC-HILIC, ZIC-cHILIC, and XBridge Amide sorbents using formic acid as eluent additive (pH 2.7). Sequence-specific retention prediction algorithms were trained using retention datasets of ∼30,000 peptides for each column. Our retention models were able to attain ∼0.98 R2-value and yielded retention coefficients that can be probed to understand peptide-stationary phase interaction. Overall, the hydrophilicity for these columns decreased when the mobile phase changed pH from 4.5 to 2.7, when using 0.1 % formic acid in the mobile phase. The acidic residues became protonated, and the resultant hydrophilic interaction is dampened at the lower pH, leaving only the basic residues as the primary hydrophilic interactors. Hence, peptides of increasing charge have higher retention. In this comparison between the three columns, ZIC-HILIC has the highest chromatographic resolution between groups of peptides of different charge. From the position-dependent retention coefficients for ZIC-HILIC at pH 2.7, we found that the amino acids at the terminal positions of the peptide modulate the basicity of the N-terminal amino group or the C-terminal Arg/Lys for tryptic peptides. With respect to the separation orthogonality between HILIC and acidic pH RPLC for two dimensional separations, the orthogonality values were lower at pH 2.7 than operating HILIC at pH 4.5 for the first dimension. We also demonstrate that ZIC-HILIC was able to distinguish citrullinated and deamidated peptides based on predicted retention values.

Hierarchical Self-Assembly and Aggregation-Induced Emission Enhancement in Tetrabenzofluorene-Based Red Emitting Molecules.

The newly synthesized chiral active [5]helicene-like tetrabenzofluorene (TBF) based highly red-emitting molecules exhibit flower-like self-assembly. These molecules display photophysical and structural properties such as intramolecular charge transfer, dual state emission, large fluorescence quantum yield, and solvatochromism. In TBFID, the indandione functional group attached on both sides as the terminal group offers an A-D-A push-pull effect and acts as a strong acceptor to cause more redshift in solution as well as in solid state as compared to TBFPA (TBF with benzaldehyde functional group in terminal position). The self-assembly studies of TBFID demonstrate the aggregation-induced emission enhancement (AIEE) attributed to the restriction of intramolecular rotation at the aggregated state. Furthermore, TBFID shows high quantum yield and intense red emission, making the molecule fit for organic light-emitting diodes (OLED) and bioimaging applications.

Synthesis and Anticancer Activity of Palladium‐Butadienyl Complexes Bearing Picolyl‐NHC and Phosphine Ligands

AbstractThis work presents the synthesis and full characterization of Pd(II)‐butadienyl complexes incorporating picolyl‐NHC or phosphine ligands (PPh3 or PTA). These complexes were evaluated against four different cancer cell lines and human lung fibroblasts. Our findings indicate a slightly lower antiproliferative activity of picolyl‐NHC Pd(II)‐butadienyl complexes compared to recently published ones featuring N−N, P−P, and C−C ligands but, above all, they exhibited selectivity for ovarian cancer cells. Additionally, trans‐[PdX (phosphine)2C4(COOMe)4Y)] derivatives (X=Br, Cl and Y=CH3, Br) proved excellent anticancer activity across all tested cancer cell lines, especially the bisPTA complexes. Importantly, the IC50 values suggest minimal impact from the halide coordinated to palladium or that present in the butadienyl terminal position. Furthermore, the low activity observed towards non‐cancerous cells underscores the potential of these synthesized Pd(II)‐butadienyl compounds as promising candidates for further investigation in anticancer research.

Design and Simulation of an Innovative Modular Four-Bar Linkage Robotic Arm: Analysis and Applications

In response to the issues of traditional manipulators, such as difficulty in controlling the terminal posture during motion, low control precision, and complex structure, a modular mechanical arm based on a parallel four-bar terminal posture maintenance mechanism has been designed to meet the special requirements of terminal posture maintenance. By analyzing the motion mechanism of the manipulator, the shape space of the manipulator, the terminal position space, and the relationships of forward and inverse kinematics have been derived. A simulation model of the linkage manipulator was established in the Robotic Toolbook for Matlab environment, and structural simulation analysis and kinematic equation verification were conducted. The end positioning and attitude control of different manipulators are simulated by Matlab programming. The working space of the manipulators is calculated by Monte Carlo method, and compared with that of traditional planar manipulators. The results show the validity of the kinematics equation and the rationality of the end positioning control scheme of the linkage manipulator. Finally, the experiment verifies that the attitude retention rate of the modular decoupling manipulator is 97.78% under high load, which verifies the reliability of this scheme. In addition, the manipulator can simplify the complexity of the mechanical structure and complete the control requirements of the terminal attitude under the premise of increasing the working space as much as possible, which lays a foundation for the design and optimization of the manipulator in the field of modular terminal attitude.

Antitumor Activity of New Pd(II) Complexes with Ligands Derived from O‐Vanillin Acting as Topoisomerase I and II Inhibitors

AbstractThis study investigates topoisomerase I and II enzyme inhibition by novel Pd(II) complexes. TSC represents the chelating ligand thiosemicarbazone, which is modified at its 4(N)‐nitrogen terminal position with substituents such as C2H5, CH3, and H. PR3 represents the triphenylphosphine ligand, with positional variations including para substituents H, F, OCH3, and CH3. The aim is to establish a correlation between these molecular variations and cytotoxicity. In particular, the compounds show promising cytotoxicity against MDA‐MB‐231 and A549 tumor cell lines, especially those with H substitution at the terminal position 4(N) of TSC and H and F in the triphenylphosphine. The results suggest that a smaller molecular volume of ligand substituents may enhance the cytotoxic effects. The inhibitory potential of the complexes against DNA topoisomerase enzymes was investigated. The IC₅₀ values of the most promising complexes strongly inhibit TOPOIIα and TOPOIβ, suggesting these enzymes as primary targets. These complexes exhibited significantly lower IC₅₀ values (4.32–4.88 μM) compared to cisplatin (10.2 μM) against MDA‐MB‐231 cells, indicating a distinct mode of action. However, it is noteworthy that the complexes did not inhibit the action of DNA topoisomerase IIβ, suggesting selectivity against specific isoforms of DNA topoisomerase II that act as catalytic inhibitors.

Cu-Electrocatalysis Enables Vicinal Bis(difluoromethylation) of Alkenes: Unraveling Dichotomous Role of Zn(CF2H)2(DMPU)2 as Both Radical and Anion Source.

The difluoromethyl group (CF2H) serves as an essential bioisostere in drug discovery campaigns according to Lipinski's Rule of 5 due to its advantageous combination of lipophilicity and hydrogen bonding ability, thereby improving the ADME properties. However, despite the high prevalence and importance of vicinal hydrogen bond donors in pharmaceutical agents, a general synthetic method for doubly difluoromethylated compounds in the vicinal position is absent. Here we describe a copper-electrocatalyzed strategy that enables the vicinal bis(difluoromethylation) of alkenes. By leveraging electrochemistry to oxidize Zn(CF2H)2(DMPU)2-a conventionally utilized anionic transmetalating source, we paved a way to utilize it as a CF2H radical source to deliver the CF2H group in the terminal position of alkenes. Mechanistic studies revealed that the interception of the resultant secondary radical by a copper catalyst and subsequent reductive elimination is facilitated by invoking the Cu(III) intermediate, enabling the second installation of the CF2H group in the internal position. The utility of this electrocatalytic 1,2-bis(difluoromethylation) strategy has been highlighted through the late-stage bioisosteric replacement of pharmaceutical agents such as sotalol and dipivefrine.

New age constraints reveal moraine stabilization thousands of years after deposition during the last deglaciation of western New York, USA

Abstract. The timing of the last deglaciation of the Laurentide Ice Sheet in western New York is poorly constrained. The lack of direct chronology in the region has led to a hypothesis that the Laurentide Ice Sheet re-advanced to near its Last Glacial Maximum terminal position in western New York at ∼ 13 ka, which challenges long-standing datasets. To address this hypothesis, we obtained new chronology from the Kent (terminal) and Lake Escarpment (first major recessional) moraines using radiocarbon ages in sediment cores from moraine kettles supplemented with two optically stimulated luminescence ages from topset beds in an ice-contact delta. The two optically stimulated luminescence ages date the Kent (terminal) position to 19.8 ± 2.6 and 20.6 ± 2.9 ka. Within the sediment cores, there is sedimentological evidence of an unstable landscape during basin formation; radiocarbon ages from the lowest sediments in our cores are not in stratigraphic order and date from 19 350–19 600 to 14 050–14 850 cal BP. We interpret these ages as loosely minimum-limiting constraints on ice sheet retreat. Our oldest radiocarbon age of 19 350–19 600 cal BP – from a rip-up clast – suggests ice-free conditions at that time. Above the lowest sediments there is organic-rich silt and radiocarbon ages in stratigraphic order. We interpret the lowest ages in these organic-rich sediments as minimum-limiting constraints on kettle basin formation. The lowest radiocarbon ages from organic-rich sediments from sites on both Kent and Lake Escarpment moraines range from 15 000–15 400 to 13 600–14 000 cal BP. We interpret the 5 kyr lag between the optically stimulated luminescence ages and kettle basin formation as the result of persistent buried ice in ice-cored moraines until ∼ 15 to 14 ka. The cold conditions associated with Heinrich Stadial 1 may have enabled the survival of ice-cored moraines until after 15 ka, and, in turn, climate amelioration during the Bølling period (14.7–14.1 ka) may have initiated landscape stabilization. This model potentially reconciles the sedimentological and chronological evidence underpinning the re-advance hypothesis, which instead could be the result of moraine instability and sediment mobilization during the Bølling–Allerød periods (14.7–13 ka). Age control for future work should focus on features that are not dependent on local climate.