Aromaticity Of Ring Research Articles

Conformational Landscape of Oxygen-Containing Naphthalene Derivatives.

Polycyclic aromatic compounds (PACs) constitute an important class of molecules found in various environments and are considered important pollutants of the Earth's atmosphere. In particular, functionalization of PACs modify the ring aromaticity, which greatly influences the chemical reactivity of these species. In this work we studied several oxygen-containing PACs, relevant to atmospheric chemistry. We investigated the conformational landscape of four naphthalene-derivative molecules-namely, 1- and 2-hydroxynaphthalene and 1- and 2-naphthaldehyde-by means of rotational and vibrational spectroscopy supported by quantum chemical calculations. For 1-hydroxynaphthalene and 1-naphthaldehyde, intramolecular hydrogen bonding and steric effects drive the conformational preferences while for 2-hydroxynaphthalene and 2-naphthaldehyde, the charge distributions allow us to understand the conformational landscape. This work not only demonstrates how the localization of the substitution group in the ring influences the conformational relative energies and but also constitutes a step toward a better understanding of the different chemical reactivity of such functionalized PACs.

Impact of the Substituents on the Electronic Structure of the Four Most Stable Tautomers of Purine and Their Adenine Analogues.

Substituent effects at the C2-, C8-, and N-positions of adenine and purine on the structural and π-electronic changes in their four tautomers were studied using the B97D3/aug-cc-pvdz computational level. The effect of various substituents (NO2, CN, CHO, Cl, F, H, Me, OMe, OH, and NH2) was characterized by the charge of the substituent active region (cSAR) approach and Hammett substituent constants σ. It has been found that for both adenine and purine derivatives, substituents from the C8–X position have a stronger influence on their electronic structure than from the C2–X and N–X positions. The presence of the amino group in adenine enhances the substituent effect compared to that which occurs in purine. In addition, its electronic structure is more sensitive to the effect of the substituent in 3H and 1H than in the 9H and 7H adenine tautomers. For a given substituent, a large variation in cSAR(X) values is observed, strongly dependent on the substitution position. For 7H and 9H adenine tautomers for C8–X systems, substituents reduce the aromaticity of the five-membered rings but increase the aromaticity of the six-membered rings.

How amino and nitro substituents affect the aromaticity of benzene ring

The effect of strongly electron-accepting and electron-donating substituents on the aromaticity of the benzene ring has been revealed based on experimental and computational data. It has been documented that the nitro group affects the π-electron structure of the ring in its benzene derivative ca. 2.8 times weaker than the amino group. However, their joint effects in the meta and para nitroaniline, compared to nitrobenzene, results in a decrease of the delocalization in the ring by a factor ca. 4.0 and 6.5, respectively.

Bond Resonance Energy Verification of σ-Aromaticity in Cycloalkanes.

The Klein-Larson bonding model is best suited for describing σ-conjugation and σ-aromaticity of cycloalkanes. Methylene groups (-CH2-) in cycloalkanes are isoconjugates with ethylene groups (-CH═CH-) in annulenes, both contributing two electrons to cyclic conjugation and aromaticity. As in the case of π-aromatic stabilization, σ-aromatic stabilization must be associated with ring-current diamagnetism. Both nucleus-independent chemical shift (NICS) and bond resonance energy (BRE) values support this interpretation. Bond resonance energy has been used to determine local ring aromaticity in nonalternant hydrocarbons, alternant hydrocarbons, heterocyclic conjugated molecules, fullerenes, pure boron clusters, and porphyrins. This contribution represents the first application of bond resonance energy toward the evaluation of σ-aromaticity/σ-antiaromaticity of polycyclic alkanes.

Understanding the Role of Aromaticity and Conformational Changes in Bond Dissociation Processes of Photo-Protecting Groups.

Photoremovable protecting groups (PPGs) provide spatial and temporal control over the release of various chemicals. Using surface hopping studies with multireference electronic structure methods we have unravelled the nuclear and the electronic events at play. Furthermore, the electronic changes along the reaction path were probed using excited state aromaticity quantifiers and orbital analysis. We find that upon irradiation with light of appropriate wavelength on the substituted coumarin system a π-π* electronic excitation occurs which is followed by an electron loss from the aromatic ring on gaining proper alignment between the π* and the C-LG (LG = leaving group) σ*. This alignment is brought about by a critical dihedral angle change in the molecule, which subsequently triggers C-LG bond cleavage. The sequence of events is indicative of an intramolecular electron catalyzed process which is established through investigations of changes in aromaticity of the phenyl ring which acts as an electron reservoir.

Synthesis and photolysis of 3-tert-butyl-4-oxy(mercapto)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazines

Reactions of 3-tert-butyl- or 3,4-di-tert-butyl-substituted 8-methylpyrazolo[5,1-c][1,2,4]-triazines with trifluoroacetic anhydride afforded 1-(2,2,2-trifluoroacetyl)-1,4-dihydropyrazolo-[5,1-c][1,2,4]triazin-4-yl 2,2,2-trifluoroacetates. The treatment with H2X and RXH (X = O or S; R = Me or Et) of covalent trifluoroacetate that does not contain the But group at the C(4) atom allowed us to synthesize 1-(3-tert-butyl-4-R-pyrazolo[5,1-c][1,2,4]triazin-1(4H)-yl)-2,2,2-trifluoroethan-1-ones. The structure of 4-ethylthio derivative was fully established by the single-crystal X-ray diffraction analysis. The UV irradiation of obtained 2,2,2-trifluoroethan-1-ones leads to the aromatization of triazine ring. The UV photolysis of 1-trifluoroacetyl-4-hydroxy derivative has been proposed as a novel method for the photogeneration of acidity. Antimicrobial and antifungal activities of the synthesized compounds were evaluated.

Application of the Intramolecular Diels–Alder Vinylarenе (IMDAV) Approach for the Synthesis of Thieno[2,3-f]isoindoles

3-(Thien-2-yl)- and 3-(thien-3-yl)allylamines, readily accessible from the corresponding thienyl aldehydes, can interact with a broad range of anhydrides and α,β-unsaturated acids chlorides (maleic, сitraconic­, and phenyl maleic anhydrides, сrotonyl and сinnamyl chlorides, etc.) leading to the formation of a thieno[2,3-f]isoindole core. Usually, the reaction sequence involves three successive steps: acylation of the nitrogen atom of the initial allylamine, the intramolecular Diels–Alder vinylarenе (IMDAV) reaction, and the final aromatization of the dihydrothiophene ring in the Diels–Alder adducts. The scope and limitations of the proposed method were thoroughly investigated. It was revealed with the aid of X-ray analysis that the key step, the IMDAV reaction, proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. In the case of maleic anhydrides, the method allows to obtain functionally substituted thieno[2,3-f]isoindole carboxylic acids, which are potentially useful substrates for further transformations and subsequent bioscreening.

Heterocyclic Anticancer compounds: Using S-NICS Method

This work is done for developing of modern anticancer drugs. Many of heterocyclic compounds are known as anticancer drugs such as alkylating agents which have targeted cell DNA causing cell death. Heterocycles’ ring structures are in essence composed by atoms other than carbon, where the most frequent substituents are sulfur, oxygen and nitrogen. In our previous work , it has been exhibited that S-NICS method is an accurate method for estimation the amount of aromaticity in the non-benzenerings similar heterocyclic rings which are popular molecules in organic chemical compounds as anti-cancer disease. Although NICS values for benzene and naphthalene and so on can be indicated as aromaticity criterion, for other molecules such as heterocyclic rings and their derivatives, S-NICS values are much more accurate compare to NICS index.

Low-pressure two-stage catalytic hydropyrolysis of lignin and lignin-derived phenolic monomers using zeolite-based bifunctional catalysts

In the present study, a two-stage catalytic hydropyrolysis of lignin was investigated by converting lignin extracted from corn stover, loblolly pine and red oak using HZSM-5, MoO3/ZSM-5 and Ni/ZSM-5 as catalysts. Compared to the catalytic pyrolysis with inert gas, the presence of atmospheric-pressure hydrogen significantly enhanced the formation of hydrocarbon from lignin whereas dramatically reducing coke yield. In comparison to HZSM-5, MoO3/ZSM-5 increased the production of aromatic hydrocarbons, while Ni/ZSM-5 enhanced the formation of aliphatic hydrocarbons. Coke yields decreased with both MoO3/ZSM-5 and Ni/ZSM-5, which corresponds to the suppression of polyaromatic formation and increased selectivity to single ring aromatics. Corn stover lignin produced the highest yield of aromatic hydrocarbons with all three catalysts, followed by loblolly pine and red oak lignins. Particularly, up to 42.24 C% of corn stover lignin was converted into aromatic and aliphatic hydrocarbons with MoO3/ZSM-5. In this study, reaction pathways of lignin-derived pyrolysis vapor during catalytic hydropyrolysis were further studied using phenol, guaiacol, and syringol as the model compounds. Results suggest that demethoxylation followed by the hydrodeoxygenation of methoxyl radicals and subsequent alkylation of the phenolic ring to produce cresol, and dimethyl phenol as intermediates prior to the intermediate phenolics were further hydrodeoxygenated to produce benzene and alkylated benzene. MoO3/ZSM-5 showed strong ability for both demethoxylation and hydrodeoxygenation. In comparison, the ability of Ni/ZSM-5 for phenolic-hydroxyl removal was much inferior. Based on the results obtained from the conversions of lignin and the model compounds, a negative correlation between the total yields of aromatic hydrocarbons from lignin and the abundancy of phenolic methoxyls in the lignin-derived pyrolysis vapor was found. It was also found that the pyrolysis vapors of simple H, G, or S-based monomers tend to produce more aromatic hydrocarbons than the vapors composed of more complex monomers and oligomers from their corresponding H, G or S group. However, the yield differences were less significant among G and S-based monomers and oligomers.

Toward Rational Understandings of α-C-H Functionalization: Energetic Studies of Representative Tertiary Amines.

SummaryFunctionalization of α-C–H bonds of tertiary amines to build various α-C–X bonds has become a mainstream in synthetic chemistry nowadays. However, due to lack of fundamental knowledge on α-C–H bond strength as an energetic guideline, rational exploration of new synthetic methodologies remains a far-reaching anticipation. Herein, we report a unique hydricity-based approach to establish the first integrated energetic scale covering both the homolytic and heterolytic energies of α-C–H bonds for 45 representative tertiary amines and their radical cations. As showcased from the studies on tetrahydroisoquinolines (THIQs) by virtue of their thermodynamic criteria, the feasibility and mechanisms of THIQ oxidation were deduced, which, indeed, were found to correspond well with experimental observations. This integrated scale provides a good example to relate bond energetics with mechanisms and thermodynamic reactivity of amine α-C–H functionalization and hence, may be referenced for analyzing similar structure-property problems for various substrates.

Superacid-promoted synthesis of quinoline derivatives

A series of vinylogous imines have been prepared from anilines and cinnamaldehydes. These substrates react in superacidic media to provide quinolines and related compounds. A mechanism for the conversion is proposed which involves the cyclization of dicationic superelectrophilic intermediates. Aromatization of the quinoline ring is thought to occur by superacid-promoted elimination of benzene.

Rational Functionalization of a C70 Buckybowl To Enable a C70:Buckybowl Cocrystal for Organic Semiconductor Applications.

Fullerene fragments, referred to as buckybowls, are garnering interest due to their distinctive molecular shapes and optoelectronic properties. Here, we report the synthesis and characterization of a novel C70 subunit, diindeno[4,3,2,1-fghi:4',3',2',1'-opqr]perylene, that is substituted with either triethylsilyl(TES)-ethynyl or 2,4,6-triisopropylphenyl groups at the meta-positions. The resulting compounds (1 and 2) display a bowl-to-bowl inversion at room temperature. Notably, the substituent groups on the meta-positions alter both the geometric and the electronic properties as well as the crystal packing of the buckybowls. In contrast to the 2,4,6-triisopropylphenyl groups in 2, the TES-ethynyl groups in 1 lead to enhanced bond length alternation, resulting in weaker aromaticity of the six-membered rings of the buckybowl skeleton. 1 forms one-dimensional (1D) concave-in-convex stacking columns, and when 1 is blended with C70, the buckybowls encapsulate C70 and result in two-dimensional cocrystals. Organic field-effect transistor (OFET) measurements demonstrate that 1 displays a hole mobility of 0.31 cm2 V-1 s-1, and the 1-C70 cocrystal exhibits ambipolar transport characteristics with electron and hole mobilities approaching 0.40 and 0.07 cm2 V-1 s-1, respectively. This work demonstrates the potential of buckybowls for the development of organic semiconductors.

Substituted adenine quartets: interplay between substituent effect, hydrogen bonding, and aromaticity.

Adenine, one of the components of DNA/RNA helices, has the ability to form self-organizing structures with cyclic hydrogen bonds (A4), similar to guanine quartets. Here, we report a computational investigation of the effect of substituents (X = NO2, Cl, F, H, Me, and NH2) on the electronic structure of 9H-adenine and its quartets (A4-N1, A4-N3, and A4-N7). DFT calculations were used to show the relationships between the electronic nature of the substituents, strength of H-bonds in the quartets, and aromaticity of five- and six-membered rings of adenine. We demonstrated how the remote substituent X modifies the proton-donating properties of the NH2 group involved in the H-bonds within quartets and how the position of the substituent and its electronic nature affect the stability of the quartets. We also showed the possible changes in electronic properties of the substituent and aromaticity of adenine rings caused by tetramer formation. The results indicate that the observed relationships depend on the A4 type. Moreover, the same substituent can both strengthen and weaken intermolecular interactions, depending on the substitution position.

Investigation of hot char catalytic role in the pyrolysis of waste tires in a two-step process

This study pursues the valorization of waste tires by pyrolysis using a different approach for tire parts, specifically, the tire tread rubber and side wall rubber. Tire tread rubber was used to produce hot char with the purpose of using it as cracking catalyst. Side wall rubber was valorized by pyrolysis and online catalytic pyrolysis over tire tread rubber derived hot char in two fixed bed reactor. This work aims to improve the quality of pyrolysis products using tire tread rubber derived hot char as catalyst. The thermal decomposition behavior and products characteristics were tested by means of TG-FTIR, GC, GC-MS, nitrogen adsorption and SEM. Under catalytic pyrolysis temperature of 500−550 °C, a high yield of valuable single ring aromatics (concentration in the oil of 50 %) was obtained. The yield of gas can reach 10.5 wt.% after catalytic pyrolysis, which only 3.0 wt.% without catalytic pyrolysis. The yield of undesirable byproducts as PAHs and carbon deposits was also limited. This strategy represents a novel and feasible alternative to traditional waste tire catalytic pyrolysis processes using expensive catalysts as zeolite.

Methanol-to-Olefins in a Membrane Reactor with in situ Steam Removal - The Decisive Role of Coking.

The reaction of methanol to light olefins and water (MTO) was studied in a fixed bed tubular membrane reactor using commercial SAPO‐34 catalyst. In the fixed bed reactor without membrane support, the MTO reaction collapsed after 3 h time on stream. However, if the reaction by‐product steam is in situ extracted from the reactor through a hydrophilic tubular LTA membrane, the reactor produces long‐term stable about 60 % ethene and 10 % propene. It is shown that the reason for the superior performance of the membrane‐assisted reactor is not the prevention of catalyst damage caused by steam but the influence of the water removal on the formation of different carbonaceous residues inside the SAPO‐34 cages. Catalytically beneficial methylated 1 or 2 ring aromatics have been found in a higher percentage in the MTO reaction with a water removal membrane compared to the MTO reaction without membrane support.

Strong Metal-Adsorbate Interactions Increase the Reactivity and Decrease the Orientational Order of OH-Functionalized N-Heterocyclic Carbene Monolayers.

Fundamental understanding of the correlation between the structure and reactivity of chemically addressable N-heterocyclic carbene (NHC) molecules on various surfacesis essential for the design of functional NHC-based self-assembled monolayers. In this work, we identified the ways by which the deposition of chemically addressable OH-NHCs on Au(111) or Pt(111) surfaces modified the anchoring geometry and chemical reactivity of surface-anchored NHCs. The properties of surface-anchored NHCs were probed by conducting X-ray photoelectron spectroscopy and polarized near-edge X-ray absorption fine structure measurements. While no preferred orientation was identified for OH-NHCs on Pt(111), the anchored molecules adopted a preferred flat-lying position on Au(111). Dehydrogenation and aromatization of the imidazoline ring along with partial hydroxyl oxidation were detected in OH-NHCs that were anchored on Au(111). The dehydrogenation and aromatization reactions were facilitated, along with partial decomposition, for OH-NHCs that were anchored on Pt(111). The spectroscopic results reveal that stronger metal-adsorbate interactions increase the reactivity of surface-anchored OH-NHCs while decreasing their molecular orientational order.

In Silico Drug-designing Studies on Sulforaphane Analogues: Pharmacophore Mapping, Molecular Docking and QSAR Modeling.

In the presented work we successfully discovered several novel NQO1 inducers using the computational approaches. The phytochemical sulforaphane (SFN) is a potent inducer of carcinogen detoxication enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1) through the Kelch-like erythroid cellderived protein with CNC homology[ECH]-associated protein 1 (Keap1)-[NF-E2]-related factor 2 (Nrf2) signaling pathway. In this paper, we report the first QSAR and pharmacophore modeling study of sulforaphane analogues as NQO1 inducers. The pharmacophore model and understanding the relationships between the structures and activities of the known inducers will give useful information on the structural basis for NQO1 enzymatic activity and lead optimization for future rational design of new sulforaphane analogues as potent NQO1 inducers. In this study, a combination of QSAR modeling, pharmacophore generation, virtual screening and molecular docking was performed on a series of sulforaphane analogues as NQO1 inducers. In deriving the QSAR model, the stepwise multiple linear regression established a reliable model with the training set (N: 43, R: 0.971, RMSE: 0.216) and test set (N: 14, R: 0.870, RMSE: 0.324, Q2: 0.80) molecules. The best ligand-based pharmacophore model comprised two hydrophobic (HY), one ring aromatic (RA) and three hydrogen bond acceptor (HBA) sites. The model was validated by a testing set and the decoys set, Güner-Henry (GH) scoring methods, etc. The enrichment of model was assessed by the sensitivity (0.92) and specificity (0.95). Moreover, the values of enrichment factor (EF) and the area under the receiver operating characteristics curve (AUC) were 12 and 0.94, respectively. This well-validated model was applied to screen two Asinex libraries for the novel NQO1 inducers. The hits were subsequently subjected to molecular docking after being filtering by Lipinski's, MDDR-like, and Veber rules as well as evaluating their interaction with three major drugmetabolizing P450 enzymes, CYP2C9, CYP2D6 and CYP3A4. Ultimately, 12 hits filtered by molecular docking were subjected to validated QSAR model for calculating their inducer potencies and were introduced as potential NQO1 inducers for further investing action. Conclusively, the validated QSAR model was applied on the hits to calculate their inducer potencies and these 12 hits were introduced as potential NQO1 inducers for further investigations.

Cytotoxicity Of Chalcone Of Eugenia aquea Burm F. Leaves Against T47D Breast Cancer Cell Lines And Its Prediction As An Estrogen Receptor Antagonist Based On Pharmacophore-Molecular Dynamics Simulation.

BackgroundThe 2ʹ,4ʹ-dihydroxy-6-methoxy-3,5-3-dimethylchalcone (ChalcEA) isolated from Eugenia aquea Burm f. leaves has potential anticancer activity against human breast-adenocarcinoma cell lines (MCF-7) with an IC50 value of 250 µM. However, its apoptotic activity on the T47D breast cancer cell lines which is involving caspase-3 has not been investigated.Materials and methodsTherefore, this study aims to evaluate the cytotoxicity of ChalcEA on the T47D cell lines using the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST) method and to predict its possible antagonistic activity on the human estrogen receptor alpha (hERα) using pharmacophore and molecular dynamics (MD) methods. The in vitro test of 10 synthesized ChalcEA derivatives was also performed as an insight into the further development of its structure as an anticancer agent.ResultsIt is shown that ChalcEA has an IC50 of 142.58 ± 4.6 µM against the hERα-overexpressed T47D breast cancer cell lines, indicating its possible mechanism of anticancer activity as an antagonist of hERα. Pharmacophore study showed that ChalcEA shares similar features with the known hERα antagonist, 4-hydroxytamoxifen (4-OHT), which has hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), ring aromaticity (RA), and hydrophobicity (Hy) features. Molecular docking showed that ChalcEA formed hydrogen bonds with Glu353 and Arg394, and hydrophobic interactions in a similar manner with 4-OHT. Moreover, MD simulations showed that ChalcEA destabilized the conformation of His524, a remarkable behavior of a known hERa antagonist, including 4-OHT. Furthermore, the 10 best chalcone derivatives resulted from pharmacophore- and docking-based screening, were tested against the T47D cell lines. None of the derivatives have better activity than ChalcEA. It is suggested that the functional groups at the B-ring of ChalcEA are interesting to be further optimized in the next studies.ConclusionChalcEA might act as an antagonist toward hERα, thus warranting further investigation as a potential anticancer agent.

Nucleolar Stress Induction by Oxaliplatin and Derivatives.

Platinum(II) compounds are a critical class of chemotherapeutic agents. Recent studies have highlighted the ability of a subset of Pt(II) compounds, including oxaliplatin but not cisplatin, to induce cytotoxicity via nucleolar stress rather than a canonical DNA damage response. In this study, influential properties of Pt(II) compounds were investigated using redistribution of nucleophosmin (NPM1) as a marker of nucleolar stress. NPM1 assays were coupled to calculated and measured properties such as compound size and hydrophobicity. The oxalate leaving group of oxaliplatin is not required for NPM1 redistribution. Interestingly, although changes in diaminocyclohexane (DACH) ligand ring size and aromaticity can be tolerated, ring orientation appears important for stress induction. The specificity of ligand requirements provides insight into the striking ability of only certain Pt(II) compounds to activate nucleolar processes.

Phosphaaluminirenes: Synthons for Main Group Heterocycles.

The phosphaaluminirenes HC[(CMe)(NDipp)]2Al[C(R)═P] (Dipp = 2,6-i-Pr2C6H3, R = tBu or adamantyl) 2 and 3, featuring an unsaturated three-membered AlCP ring, have been synthesized as crystalline solids via a [1 + 2] cycloaddition reaction of the aluminum(I) complex HC[(CMe)(NDipp)]2Al (1) with phosphaalkynes. Computational investigations infer three-centered 2π-electron aromaticity of the AlCP rings. Compound 3 is readily protonated by tBuOH to induce a ring-opening σ-bond metathesis, giving an alumina-substituted P-hydrogeno phosphaalkene 4. Remarkably, the high strain of the AlCP ring of 3 allows for facile ring enlargement in reactions with CyNC, bis(diisopropylamino) cyclopropenylidene (BAC), elemental Se, Ph2CO, PhCH═CHCOPh, and PhCN at room temperature. These furnish a series of unprecedented main group heterocycles 5-10 with the C═P unsaturated bonds remaining intact. The mechanisms are considered in light of thorough density functional theory (DFT) calculations.