Position Of Substituents Research Articles

Cyclometalated Benzimidazole Osmium(II) Complexes with Antiproliferative Activity in Cancer Cells Disrupt Calcium Homeostasis.

We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)2]OTf (N^N = 2,2'-bipyridine and dipyrido[3,2-d:2',3'-f]quinoxaline; C^N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiproliferative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.

New cationic spiropyrans with photoswitchable NIR fluorescence

Visible-light-mediated photochromic compounds with NIR absorption and fluorescence are of great interest for use in different biomedical applications. In this work, new representatives of spiropyrans with conjugated cationic 3H-indolium substituents in different positions of 2H-chromene moiety were synthesized. The electron-donating methoxy groups were introduced in the uncharged indoline and charged indolium cycles to form the effective conjugation chain between the hetarene moiety and the cationic fragment for reaching NIR absorption and fluorescence. The molecular structure and the effects of cationic fragment position on the mutual stability of the spirocyclic and merocyanine forms of compounds were carefully studied in the solutions and solid state by NMR, IR, HRMS, single-crystal XRD, and quantum chemical calculations. It was found that the obtained spiropyrans demonstrate positive or negative photochromism depending on the cationic fragment’s position. One of spiropyrans has shown bidirectional photochromic properties induced exclusively by visible light of different wavelengths in both directions. The photoinduced merocyanine forms of compounds possessed far-red shifted absorption maxima and NIR fluorescence, which makes them prospective fluorescent probes for bioimaging.

Protocol for structure determination of unknowns by EI mass spectrometry. II. Diagnostic ions in one ring alicyclic, heterocyclic, and aromatic compounds

Electron ionization (EI) mass spectra of saturated carbocyclic hydrocarbons containing a single ring with three or more members are discussed followed by the examination of their unsaturated analogs, including aromatic hydrocarbons. Mass spectrometry characteristics of heterocyclic compounds for each cycle size with one, two, three, and more hetero-atoms in a ring are considered along with their mono- and polyunsaturated analogs. An effect of the (a) size of a cycle; (b) number, nature, and location of elements in a ring; (c) position and nature of ring substituents; and (d) nature and location of unsaturation on the dissociation is revealed. Characteristic dissociation directions of these compounds and diagnostically important ions in their spectra are identified. Basic dissociation rules for alicyclic, heterocyclic, and aromatic compounds under EI are established for further use in the analysis of complex chemicals containing these structural elements.

Discriminating Aromatic Parent Compounds and Their Derivative Isomers in Ice Grains From Enceladus and Europa Using a Laboratory Analogue for Spaceborne Mass Spectrometers

AbstractResults from the Cassini‐Huygens space mission at Enceladus revealed a substantial inventory of organic species embedded in plume and E ring ice grains originating from a global subsurface and putative habitable ocean. Compositional analysis by the Cosmic Dust Analyzer indicated the presence of aromatic species and constrained some structural features, although their exact nature remains unclear. As indicated by many studies, among other organic species, low‐mass aromatics likely played a role in the emergence of life on Earth and may be linked to potential prebiotic or biogenic chemistry on icy moons. Here, we study the behavior of single‐ringed aromatic compounds—benzoic acid and two isomeric derivatives, 2,3‐dihydroxybenzoic acid and 2,5‐dihydroxybenzoic acid—using Laser‐Induced Liquid Beam Ion Desorption (LILBID), an analogue setup to simulate the impact ionization mass spectra of ice grains in space. These compounds share common structural features but also exhibit differences in functional groups and substituent positions. We investigate the fragmentation behavior and spectral appearance of each molecule over three simulated impact velocities, in both positive and negative ion modes. Parent compounds can be distinguished easily from their derivatives due to various spectral differences, including the (de)protonated molecular ion peaks appearing at different m/z values. We conclude that distinction between structural isomers in LILBID is more challenging, but some insights can be revealed by considering intermolecular bonding regimes. This work will guide future investigations into elucidating the composition of isomeric biosignatures in ice grains, relevant for future space missions to Enceladus and Europa.

Tetrachlorosubstituted Lead Phthalocyanines: Effect of the Positions of Substituents on the Structure of Single Crystals and thin Films

Tetrachlorosubstituted Lead Phthalocyanines: Effect of the Positions of Substituents on the Structure of Single Crystals and thin Films

Neuro-Evolutive Modeling of Transition Temperatures for Five-Ring Bent-Core Molecules Derived from Resorcinol

Determining the phase transition temperature of different types of liquid crystals based on their structural parameters is a complex problem. The experimental work might be eliminated or reduced if prediction strategies could effectively anticipate the behavior of liquid crystalline systems. Neuro-evolutive modeling based on artificial neural networks (ANN) and a differential evolution (DE) algorithm was applied to predict the phase transition temperatures of bent-core molecules based on their resorcinol core. By these means, structural parameters such as the nature of the linking groups, the position, size and number of lateral substituents on the central core or calamitic wings and the length of the terminal chains were taken into account as factors that influence the liquid crystalline properties. A number of 172 bent-core compounds with symmetrical calamitic wings were selected from the literature. All corresponding structures were fully optimized using the DFT, and the molecular descriptors were calculated afterward. In the first step, the ANN-DE approach predicted the mesophase presence for the analyzed compounds. Next, ANN models were determined to predict the transition temperatures and whether or not the bent-core compounds were mesogenic. Simple structural, thermophysical and electronic structure descriptors were considered as inputs in the dataset. As a result, the models determined for each individual temperature have an R2 that varied from 0.89 to 0.98, indicating their capability to estimate the transition temperatures for the selected compounds. Moreover, the impact analysis of the inputs on the predicted temperatures showed that, in most cases, the presence or not of liquid crystalline properties represents the most influential feature.

Fluorination Improves the Electro-Optical Properties of Benzoxazole-Terminated Liquid Crystals in High Birefringence Liquid Crystal Mixtures: Experimental and Theoretical Investigations.

Aromatic heterocyclic liquid crystal (LC) materials have received much attention from LC chemists for their high birefringence and large dielectric anisotropy, yet few have reported their properties in LC mixtures. In this work, a series of fluorinated benzoxazole liquid crystal compounds were synthesized to evaluate their electro-optical properties in high birefringence LC mixtures, with the expectation of further establishing the theoretical basis and experimental evidence for their applications in LC photonics. Firstly, the effects of the lateral fluorine substituent positions on the molecular synthetic yield, mesomorphic and solubility properties were comparatively investigated. Afterwards, we focused on the fluorination effects on the core electro-optical properties, including birefringence, dielectric anisotropy and further investigation of the viscoelastic coefficient of high birefringence LC mixtures. Research results showed that the benzoxazole liquid crystal compounds possess low melting points, wide nematic phase intervals and good solubility by appropriate lateral fluorine substitution, which is beneficial to further improve the electro-optical properties of high birefringence LC mixtures. Meanwhile, the theoretical and experimental results corroborate each other to well reveal the structure-property relationship. This study demonstrates that fluorination would promote promising applications of benzoxazole-terminated liquid crystals in emerging LC optical devices.

Structural and Magnetic Investigation of Cobalt Valence Tautomeric Complexes with Sulfur-Containing Ligands

We report a series of heteroleptic cobalt complexes of the general formula [Co(tBu2sq)2(L)2], where tBu2sq = 3,5-di(tert-butyl)-o-semiquinonato ligand and L represents pyridines functionalized with sulfur-containing substituents. The octahedral coordination of the Co metal center in these mononuclear complexes is formed by two chelating tBu2sq ligands in the equatorial plane and two axial pyridines in the axial positions. All complexes exhibit layered crystal packings, with S-containing substituents providing cohesion within the layers and the tBu substituents of dioxolenes protruding into the interlayer space, where disordered solvent molecules are located. The presence of thienyl substituents in the para position of the pyridine ring leads to the formation of molecular chains within the layers, due to efficient π–π interactions between the L ligands. Even more efficient packing with two-dimensional intermolecular π–π interactions is achieved when two thienyl substituents are present in the meta positions of the pyridine ring. Introduction of a terminal cyano or 1,3-dithiole-2-one substituent on the opposite end of the pyridyl-bound thienyl group leads to the disruption of the π–π interactions, thus decreasing the crystal packing efficiency. Such disruption, however, is not observed when the thienyl group is terminated with methyl-carboxylate. Magnetic measurements reveal an onset of valence-tautomeric spin-crossover (VT-SCO) from the [LS-CoIII(tBu2sq•)(tBu2cat)(L)2] state (low-spin, S = 1/2) to the [HS-CoII(tBu2sq•)2(L)2] state (high-spin, S = 5/2) above 300 K for the complexes with para-thienyl-substituted pyridines, while the complexes with a bithienyl substituent in the para position or two thienyl substituents in the meta positions exhibit only LS state up to 400 K. Adding a terminal group to the para-thienyl substituent lowers the VT-SCO temperature, leading to two-step spin-state conversion.

Molecular engineering of benzenesulfonyl analogs for visual hydrogen polysulfide fluorescent probes based on Nile red skeleton

Hydrogen polysulfide (H2Sn, n > 1) has a valuable function in various aspects of biological regulation. Therefore, it is of great significance to realize the visual monitoring of H2Sn levels in vivo. Herein, a series of fluorescent probes NR-BS were constructed by changing types and positions of substituents on the benzene ring of benzenesulfonyl. Among them, probe NR-BS4 was optimized due to its wide linear range (0 ∼ 350 μM) and little interference from biothiols. In addition, NR-BS4 has a broad pH tolerance range (pH = 4 ∼ 10) and high sensitivity (0.140 μM). In addition, the PET mechanism of probe NR-BS4 and H2Sn was demonstrated by DFT calculations and LC-MS. The intracellular imaging studies indicate that NR-BS4 can be successfully devoted to monitor the levels of exogenous and endogenous H2Sn in vivo.

Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford an isoindolinone with aminal substituent in 3-position in suitable selectivity. The use of Takemoto's bifunctional organocatalyst not only led to observed enantioselectivity but was also important in accomplishing the cyclization step in both cases. Notably, this catalytic system proved to be particularly effective in comparison to widely used phase transfer catalysts.

Ruthenium (0) complexes with NHC tetrazolylidene ligands: Synthesis, characterization and reactivity

Here we present two new phenyl-tetrazolylidene carbenes as ligands in non-mesoionic (1,4-substitution pattern) and mesoionic (1,3-substitution pattern) tetrazolylidene-cyclopentadienone ruthenium(0) complexes namely 1 and 2 respectively. The complexes have been obtained in good yield and fully characterized; X-ray structure determination confirmed the binding mode of the ligand for 2. Reactivity studies has been performed in order to shed light on the fact that the phenyl substituent position in the heterocyclic ligand can seriously change complexes behavior and stability.

Quest for a Rational Molecular Design of Alkyl-Distyrylbenzene Liquid by Substitution Pattern Modulation.

Alkyl-π functional molecular liquids (FMLs) are of interest for fabricating soft electronic devices due to their fluidic nature and innate optoelectronic functions from the π-conjugated moiety. However, predictable development of alkyl-π FMLs with the desired liquid and optoelectronic properties is challenging. A series of alkyl-distyrylbenzene (DSB) liquids was studied in terms of the substituent position effect by attaching 2-octyldodecyl chains at (2,4-), (2,5-), (2,6-), and (3,5-). The effect of the alkyl chain length was investigated by attaching 2-hexyldecyl, 2-decyltetradecyl (C10 C14 ), and 2-dodecylhexadecyl at the (2,5-) substituent position. The 2,5-C10 C14 substituent pattern constructed a superior alkyl-DSB liquid with a lower viscosity, intrinsic optical properties, and high thermal- and photo-stabilities. The discovered 2,5-C10 C14 was applied to dicyanostyrylbenzene and comparable liquid physical and optical superiorities were confirmed. This molecular design is useful for creating alkyl-π FMLs with the aforementioned advantages, which are applicable for deformable and flowable optoelectronic devices.

Modulating the Roaming Dynamics for the NO Release in ortho-Nitrobenzenes

The dynamics of NO release upon photodissociation of nitroaromatic compounds is dependent on the nature of the interaction between the NO2 group and substituent in the ortho position. A bimodal (slow and fast) translational energy distribution of the NO photofragment indicates the presence of two distinct NO elimination channels. The slow-to-fast branching ratio for the NO release is regulated by the hydrogen bonding ability of the ortho substituent and follows the order [OH > NH2 > CH3 > OCH3], indicating that the intramolecular hydrogen bonding plays a pivotal role in NO release dynamics. Further, the topology of the triplet state potential energy surface acts as a doorway to the dissociation pathway switching between the roaming and nonroaming mechanisms, with hydrogen bonding substituents (OH and NH2) favoring the roaming mechanism.

Thermal and photochemical reactions of n-pyridinebenzopyrylium multistate of species (n = 2′,3′,4′). Exploring the synthetic potentialities from the unique reactivity of position 2′

The kinetics and thermodynamics of the pH-dependent multistate of species generated by the trans-chalcone of n-pyridinebenzopyrylium (n = 2′, 3′) were studied by UV–vis spectroscopy, 1H NMR and HPLC-MS, and the results compared with those reported for n = 4′. Due to the slow kinetics of the multistate species interconversion, the conjugation of these techniques has shown to be a powerful tool to investigate the behaviour of these systems. The species involved in the multistate are mutatis mutandis the same observed in anthocyanins and related compounds except for the flavylium cation, which was not observed in these systems even in very acidic medium. The rates of the interconversion of the multistate species upon pH stimuli are much slower than in anthocyanins. The compound bearing the pyridine nitrogen in position 2′ gives two novel products absorbing in the visible. Formation of the new products is particularly efficient from the thermal evolution of the photochemical products obtained upon light irradiation of the protonated trans-chalcone in a mixture of methanol:acidic water (1:1). This confirms the unique capacity of the substituents in position 2′ in giving intramolecular reactions involving the benzopyrylium core. Crystal structures for the three pyridine chalcone compounds (n = 2′, 3′, 4′) were obtained and the respective structures discussed.

Chain-Length Induced Structural Polymorphism for two-dimension self-assembly

Structural polymorphism obtained through the 2D self-assembly which was made use of the chain-ength induced, has has aroused wide concern. On the one hand, owing to its significance meaning in crystal engineering, on the other hand, it has a broad application prospect in nano science and technolog.The assembly of symmetric 2, 7-bis (n-alkoxy) -9-fluorenone(F-OCn) with varying lengths of peripheral alkyl chains dissolved in homologous acids was investigated. The size and shape of molecules and the structure and position of substituents were critical factors that regulate the equilibrium of the interaction and formation of self-assembled patterns. Useing altered the symmetry and chain-length of the molecular structure, the self-assembly morphology and cellular properties can be predicted. The self-assembled strcture displayed the assembly of F-OCn (11-14). “S” shaped and alternating phases are the thermodynamic stable states. The competition between van der Waals forces from the interdigital alkyl chains and van der Waals forces between molecule-substrate takes effect. The vdW forces between the molecule-substrate was predominant when n varies from 15 to 18. The observation of the chain-length effects and odd-even effects showed that: F-OCeven developed from a loose-and close-packed patterns to a dislocated zigzag patterns.Self-assembled morphology of F-OCodd evolved from a well-distributed trimer monolayer to the dislocated zigzag pattern.These researches offers insight into the structural diversity by regulating the alkyl side chain-length and odd-even effects on two-dimension self-assembly and the construct a new molecular materials.

Design, Synthesis and Biological Evaluation of Novel Quinoline Derivatives as Potential Anti-Proliferative Agents Against PC-3 and KG-1 Cells.

Cancer is a major public health problem worldwide, and is the leading cause of death. The discovery and development of cancer therapeutic drugs have become the most urgent measure, which significantly benefited from the usage of small molecule compounds. The quinoline core possessed a vast number of biological activities that were found to be imperative. The aim is to design, synthesize and perform the biological evaluation of novel quinoline derivatives as potential anti-proliferative agents. Quinoline as a privileged scaffold was adopted to introduce diverse effective nitrogen heterocycles through different linkers. The synthesized compounds were spectroscopically characterized and evaluated for their anti-proliferative activity using the CCK8 assay. The mechanism of action was investigated by flow cytometry and the inhibitory activity against Pim-1 kinase was measured by mobility shift assay. Molecular docking analysis was performed to rationalize biochemical potency as well. The majority of these quinolines displayed potent growth inhibitory effects, among which compounds 13e, 13f and 13h were the most effective ones, with GI50 values of 2.61/3.56, 4.73/4.88 and 4.68/2.98 μM, respectively. Structure-activity relationships indicated that both appropriate heterocycles at the C4 position of pyridine and suitable substituent at quinoline had a significant impact on improving activity. Compounds 13e and 24d exhibited moderate Pim-1 kinase inhibitory activity. In this study, three series of novel molecules bearing quinoline scaffold were designed, synthesized and evaluated for their in-vitro anti-proliferative activity. The most promising candidate, 13e, caused cell cycle arrest in a concentration-dependent manner and further induced apoptosis, which might represent a novel antiproliferative agent working through Pim-1 kinase inhibition to a certain extent.

Luminescent furo[2,3-c]isoquinolines as fluorophores - Tuning the luminophore by donor substitution

A new library of the uncommon furo[2,3-c]isoquinoline scaffold has been synthesized by coupling the Ugi multicomponent reaction with a complex one-pot Pd-mediated double cyclization. The highly convergent and diversity-oriented approach has been exploited to introduce substituents with electron donor properties directly linked to the scaffold in the most representative positions 1 and/or 8. Moreover, the influence of an aromatic ring used as spacer between the scaffold and the electron donor substituent, as well as the substitution of the phenyl substituent in position 1 with a thiophene, on the photophysical properties have been investigated. Upon UV excitation part of the new molecules are intensively blue luminescent but for an amino donor substituent a significant switch to green emitters has been observed even upon eyesight. The electronic structure has been semiquantitatively rationalized by DFT and (TD)DFT calculations.

Spontaneous polymerization of benzofulvene monomers bearing a 4-Pyridylacetylene substituent in different positions of the benzofulvene scaffold

Two benzofulvene derivatives bearing a 4-pyridylacetylene substituent in different positions (i. e. 2 and 6) of the benzofulvene scaffold are designed and synthesized to evaluate the effects on the spontaneous solid-state polymerization of the presence of the same substituent in two different key positions of the 3-phenylbenzofulvene moiety. Both the benzofulvene derivatives showed the tendency to polymerize spontaneously in the consequence of solvent removal under reduced pressure without the addition of catalysts or initiators. The macromolecular structure of the stemming polymeric materials was investigated by NMR spectroscopy and MALDI-TOF mass spectrometry. Both NMR and MALDI-TOF studies confirmed the polymeric nature of the materials and suggested for the polybenzofulvene derivative bearing the 4-pyridylacetylene substituent in positions 6 a higher structural homogeneity with respect to the one bearing the same substituent in position 2. The photophysical characterization of the most homogeneous polybenzofulvene derivative led to the discovery of its outstanding hole mobility value, which was found to be around one order of magnitude higher than that previously measured for two oligothiophene-based polybenzofulvene derivatives and almost two orders of magnitude higher than that of poly(vinylcarbazole), commonly used as hole-transporter matrix. This result places the new polybenzofulvene derivative in an outstanding position as a promising material for field-effect transistor (FET) device applications.

Effect of Substituent Location on the Relationship between the Transition Dipole Moments, Difference Static Dipole, and Hydrophobicity in Squaraine Dyes for Quantum Information Devices.

Aggregates of organic dyes that exhibit excitonic coupling have a wide array of applications, including medical imaging, organic photovoltaics, and quantum information devices. The optical properties of a dye monomer, as a basis of dye aggregate, can be modified to strengthen excitonic coupling. Squaraine (SQ) dyes are attractive for those applications due to their strong absorbance peak in the visible range. While the effects of substituent types on the optical properties of SQ dyes have been previously examined, the effects of various substituent locations have not yet been investigated. In this study, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were used to investigate the relationships between SQ substituent location and several key properties of the performance of dye aggregate systems, namely, difference static dipole (Δd), transition dipole moment (μ), hydrophobicity, and the angle (θ) between Δd and μ. We found that attaching substituents along the long axis of the dye could increase μ while placement off the long axis was shown to increase Δd and reduce θ. The reduction in θ is largely due to a change in the direction of Δd as the direction of μ is not significantly affected by substituent position. Hydrophobicity decreases when electron-donating substituents are located close to the nitrogen of the indolenine ring. These results provide insight into the structure-property relationships of SQ dyes and guide the design of dye monomers for aggregate systems with desired properties and performance.

In Search of Hosts for Blue OLEDs: Computational Design and Experimental Validation.

Considering the difficulties associated with the conventional 'trial and error' method for a complete analysis of a giant molecular space, we took the aid of computational pathway (DFT) in screening a large space search of 780 (12×13×5) molecules to search for a host for the blue emitter. The selection process was completed in three Tiers with the conditions of highest theoretical triplet energy (>2.81 eV), aligned HOMO/LUMO levels w.r.t blue dopant (FIrpic), and position of substituents to meet the optimal requirements as host materials. Tier 1 screened twelve different imidazole heterocycle derivatives as base space groups which resulted in the selection of 4,5-diphenyl-1H-imidazole. Tier 2 process converged the search to mCN-CZ having the highest triplet energy and appropriate HOMO/LUMO level relative to FIrpic and ETL. Further, the carbazole of mCN-CZ was replaced with different aromatic hydrocarbons to find the other best compound in terms of triplet energy and HOMO/LUMO. Tier 3 resulted in another promising candidate (mCN-FL) as possible host materials. The band alignment with guest predicted mCN-FL and mCN-CZ to have optimal device performances compared to CZ-CZ and the experimentally observed device performance was in accordance with virtual screening results when TAPC was utilized as the hole transporter. The device results of mCN-CZ and mCN-FL were better than the reference host TCTA. The obtained results thus proved that a virtual screening process will be a useful tool for synthetic chemists in designing task-specific materials.