Aromaticity Of Ring Research Articles

Theoretical Molecular Design of Heteroacenes for Singlet Fission: Tuning the Diradical Character by Modifying π-Conjugation Length and Aromaticity

A theoretical molecular design for efficient singlet fission (SF) is performed for several heteroacene models involving nitrogen (N) atoms based on the diradical character criterion of the energy level matching conditions. This criterion is found to be closely related to the relative contributions of diradical and zwitterionic resonance structures of the heteroacenes, i.e., the aromaticity of the central ring(s). From the analysis of the diradical characters of these heteroacene models, the increase in the aromaticity of the central ring(s) is found to prefer the diradical form to the zwitterionic form. From the comparison of the excitation energies evaluated by multireference second-order perturbation theory calculations, two promising candidates, chosen based on the diradical character criterion, are found to satisfy the energy level matching conditions and to possess high triplet energies of ∼1.1 eV, which are suitable for an application in organic photovoltaic cells. The proposed two candidates are shown to have mutually different types of the first excited singlet states, which are distinguished by the primary excitation configurations. These results suggest that the proposed two candidates exhibit different singlet fission dynamics due to the different amplitude of the electronic coupling.

The mechanism of human aromatase (CYP 19A1) revisited: DFT and QM/MM calculations support a compound I-mediated pathway for the aromatization process

Human aromatase is responsible for the last step of estrogen biosynthesis, for the aromatization of ring A of androstenedione or testosterone. In this work, the mechanism of aromatization was studied using gas phase and hybrid QM/MM calculations. It is shown that human aromatase can efficiently catalyze the aromatization process via a compound I (or compound II)-mediated pathway. The nature of the oxidant is very sensitive to the polarizing environment of the enzyme, as the oxidant has a compound I nature in the gas phase calculations, which is modulated by the enzyme environment to become a mixed compound I and compound II character. The electronic structure of the obtained QM-only and QM/MM stationary points is thoroughly discussed.

Effect of benzo-annelation on local aromaticity in heterocyclic conjugated compounds.

The effect of benzo-annelation on the local aromaticity of the central ring of acridine (1), 9H-carbazole (2), dibenzofuran (3), and dibenzothiophene (4) was analyzed by means of the energy effects (ef), pairwise energy effects (pef), multicenter delocalization index (MCI), electron density at ring critical points (ρ(r(C))), harmonic oscillator model of aromaticity (HOMA), and nucleus independent chemical shifts (NICS). According to energetic, electron delocalization, and geometrical indices, angular benzo-annelation increases, whereas linear benzo-annelation decreases, the extent of the local aromaticity of the central ring containing heteroatoms. The local aromaticity of the central heterocyclic ring in the examined molecules can significantly vary by applying different modes of benzo-annelation. The NICS values do not always support the results obtained by the other aromaticity indices and, in some cases, lead to completely opposite conclusions.

Substituent Effect of Nitro Group on Aromaticity of Carbazole Rings

The molecular geometries of carbazole and its 17 nitro derivatives were optimized at the B3LYP/6-311++G(2d,2p) level of theory. The harmonic oscillator model of aromaticity and nucleus-independent chemical shift descriptors of π-electron delocalization were calculated to estimate the aromaticity of the carbazole five- and six-membered rings. The biggest changes in the value of both descriptors were observed for the pyrrole ring. The nitro group attached to 3 and/or 6 positions of the carbazole ring system exerts only a slight influence on the benzene ring aromaticity.

Two pyrolysate products from Omani frankincense smoke: First evidence of thermal aromatization of boswellic acids

The frankincense resin of botanically-certified Boswellia sacra was pyrolyzed and the smoke was trapped into water using self-developed assembly. Two compounds, namely 1,2,4a,9-tetramethyl-1,2,3,4,4a,5, 6,14b-octahydropicene (1) and 2,9-dimethylpicene (2) were isolated from n-hexane extract of the smoke-saturated water. Their structures were determined by means of spectroscopic data including ESIMS, 1H NMR, 13C NMR, and 2D NMR (COSY, HSQC, HMBC, and NOESY). Dehydration of C-3 alcohols in boswellic acids (BAs) lead to aromatization of ring A followed by dehydrogenation and demethylation to afford triaromatic derivative viz., 1,2,4a,9-tetramethyl-1,2,3,4,4a,5, 6,14b-octahydropicene (1) and finally penta-aromatic derivative viz., 2,9-dimethylpicene (2). Compounds 1 and 2 were screened for their antiproliferative effects on MDA-MB-231 breast cancer cells. It was found that these pyrolysate products were capable of inhibiting cancer cell growth. However, this growth inhibitory effect was less when compared to their precursor AKBA (3-acetyl-11-keto-β-boswellic acid). The antiproliferative activity is inversely proportional to loss of functional groups.

Ring currents in benzo- and benzocyclobutadieno-annelated biphenylene derivatives.

The effect of benzo and benzocyclobutadieno annelation on the current density induced in a series of biphenylene derivatives is examined at the B3LYP/cc-pVDZ level of theory, by using the CTOCD-DZ method. Angular benzo annelation increases, whereas linear benzo annelation decreases the intensity of paratropic (antiaromatic) current density along the four-membered ring of biphenylene. The opposite effect is found for benzocyclobutadieno annelation. It is shown that the extent of local aromaticity of the four-membered ring in biphenylene congeners can vary from highly antiaromatic to nonaromatic, as a result of different modes of annelation.

Reactivity of damaged pyrimidines: DNA cleavage via hemiaminal formation at the C4 positions of the saturated thymine of spore photoproduct and dihydrouridine.

Described here are mechanistic details of the chemical reactivities of two modified/saturated pyrimidine residues that represent naturally occurring forms of DNA damage: 5-thyminyl-5,6-dihydrothymine, commonly referred to as the “spore photoproduct” (SP), and 5,6-dihydro-2′-deoxyuridine (dHdU), formed via ionizing radiation damage to cytosine under anoxic conditions and also serving as a general model of saturated pyrimidine residues. It is shown that due to the loss of the pyrimidine C5–C6 double bond and consequent loss of ring aromaticity, the C4 position of both these saturated pyrimidines is prone to the formation of a hemiaminal intermediate via water addition. Water addition is facilitated by basic conditions; however, it also occurs at physiological pH at a slower rate. The hemiaminal species so-formed subsequently converts to a ring-opened hydrolysis product through cleavage of the pyrimidine N3–C4 bond. Further decomposition of this ring-opened product above physiological pH leads to DNA strand break formation. Taken together, these results suggest that once the aromaticity of a pyrimidine residue is lost, the C4 position becomes a “hot spot” for the formation of a tetrahedral intermediate, the decay of which triggers a cascade of elimination reactions that can under certain conditions convert a simple nucleobase modification into a DNA strand break.

Exploratory breath analyses for assessing toxic dermal exposures of firefighters during suppression of structural burns

Firefighters wear fireproof clothing and self-contained breathing apparatus (SCBA) during rescue and fire suppression activities to protect against acute effects from heat and toxic chemicals. Fire services are also concerned about long-term health outcomes from chemical exposures over a working lifetime, in particular about low-level exposures that might serve as initiating events for adverse outcome pathways (AOP) leading to cancer. As part of a larger US National Institute for Occupational Safety and Health (NIOSH) study of dermal exposure protection from safety gear used by the City of Chicago firefighters, we collected pre- and post-fire fighting breath samples and analyzed for single-ring and polycyclic aromatic hydrocarbons as bioindicators of occupational exposure to gas-phase toxicants. Under the assumption that SCBA protects completely against inhalation exposures, any changes in the exhaled profile of combustion products were attributed to dermal exposures from gas and particle penetration through the protective clothing. Two separate rounds of firefighting activity were performed each with 15 firefighters per round. Exhaled breath samples were collected onto adsorbent tubes and analyzed with gas-chromatography-mass spectrometry (GC-MS) with a targeted approach using selective ion monitoring. We found that single ring aromatics and some PAHs were statistically elevated in post-firefighting samples of some individuals, suggesting that fire protective gear may allow for dermal exposures to airborne contaminants. However, in comparison to a previous occupational study of Air Force maintenance personnel where similar compounds were measured, these exposures are much lower suggesting that firefighters’ gear is very effective. This study suggests that exhaled breath sampling and analysis for specific targeted compounds is a suitable method for assessing systemic dermal exposure in a simple and non-invasive manner.

Substituents and environment influences on aromaticity of peri- and para-substituted naphthalenes.

The influence of substituents and environment on the aromaticity of the naphthalene ring is shown for a series of peri- and para-substituted naphthalenes. Crystal structure geometries are compared with the single molecule structures in vacuum (optimized at the B3LYP/6-311++G** level) and with structures determined in media of different polarity. The harmonic oscillator model of aromaticity (HOMA) index of the naphthalene rings has been used to characterize the aromaticity of the investigated molecules. It has been shown that the ellipticity of the C2-C3 (C6-C7) bonds can be applied as a measure of participation of the quinoid resonance structure and through-resonance effect between the para-substituents.

Fuel properties and chemical compositions of the tar produced from a 5 MW industrial biomass gasification power generation plant

The industrial biomass gasification tar (IBGT) was analyzed for its basic fuel properties and chemical compositions. The results suggested that IBGT had some special properties (high water content, high ash content, high viscosity, etc.). IBGT was subjected to extraction to obtain n-hexane soluble, n-hexane insoluble/toluene soluble, toluene insoluble/tetrahydrofuran soluble, and tetrahydrofuran insoluble fractions, which were characterized by FTIR. The n-hexane soluble fraction was further fractionated by column chromatography into four fractions, which were characterized by gas chromatography-mass spectrometry (GC/MS). The n-hexane insoluble/toluene soluble and toluene insoluble/tetrahydrofuran soluble fractions were characterized by 1H NMR. The results showed that the first fraction (6.96 wt.%) contained alkanes and alkenes; the second fraction (15.68 wt.%) contained 1–3 ring aromatics; the third fraction (29.20 wt.%) contained oxygen compounds, such as phenols; the fourth fraction (6.40 wt.%) contained nitrogen compounds, such as quinoline, isoquinoline, amine and amide; the fifth fraction (21.07 wt.%) mainly contained polycyclic aromatic structure with short aliphatic side chain and long aliphatic bridge bond; the sixth fraction (12.32 wt.%) mainly contained polycyclic aromatic structure with heteroatom side chain; the seventh fraction (8.38 wt.%) contained ash, coke and unreacted biomass. These results may present an effective solution to utilization of IBGT.

A B3LYP and MP2(full) theoretical investigation into cooperativity effects, aromaticity and thermodynamic properties in the Na+⋯benzonitrile⋯H2O ternary complex

The cooperativity effects between H-bonding and Na(+)⋯π or Na(+)⋯σ interactions in Na(+)⋯benzonitrile⋯H2O complexes were investigated using the B3LYP and MP2(full) methods with 6-311++G(2d,p) and aug-cc-pVTZ basis sets. The thermodynamic cooperativity and the influence of this cooperativity on aromaticity was evaluated by nucleus-independent chemical shifts (NICS). The results showed that the influence of the Na(+)⋯σ or Na(+)⋯π interaction on the hydrogen bond is more pronounced than that of the latter on the former. The cooperativity effect appeared in the Na(+)⋯σ interaction complex while the anti-cooperativity effect tended to be in the Na(+)⋯π system. The change in enthalpy is the major factor driving cooperativity. Thermodynamic cooperativity is not in accordance with the cooperativity effect evaluated by the change of interaction energy. The ring aromaticity of is weakened while the bond dissociation energy (BDE) of the C-CN bond increases upon ternary complex formation. The cooperativity effect (E coop) correlates with R c (NICS(1)ternary/NICS(1)binary) and ΔΔδ (Δδ ternary - Δδ binary) involving the ring and C ≡ N bond, as well as R BDE(C-CN) [BDE(C-CN)ternary/BDE(C-CN)binary], respectively. AIM (atoms in molecules) analysis confirms the existence of cooperativity.

Tuning the Aromaticity of s-Triazine in the Crystal Phase by Pressure

The effect of pressure on the electronic properties of crystalline s-triazine has been studied up to 14 GPa by using two-photon induced fluorescence. Emission and excitation spectra have been measured as a function of pressure on samples compressed in a diamond anvil cell. The different two-photon absorption cross sections to the nπ* and ππ* excited states account for the selectivity in the excitation wavelength observed in the high pressure photoinduced reactivity. The comparison between excitation and emission spectra highlights a remarkable red shift with rising pressure of the higher electronic excited states having ππ* character, which contrasts with the pressure insensitivity of the lowest nπ* states. Pressure is therefore extremely efficient at progressively destabilizing the π bonding orbitals, causing a reduction of the ring aromaticity, and driving the high pressure reactivity.

Clar theory extended for polyacenes and beyond.

An extension of Clar's classical sextet ideas is presented to allow resonance-based weak-pairing long bonds. As the prototypic illustration, the theory is developed in the context of polyacenes, where this extension is needed to properly understand what goes on in this sort of polymer, whose radicality increases with chain length. A quantification of these novel Clar-sextic ideas is made, and detailed computational results are reported for the polyacenes even to the limit of arbitrary long chains. Resonance energies, bond lengths, and local (ring) aromaticity indices are addressed. It is emphasized that weak pairing is not at all unique to the polyacenes, but also applies whenever there are suitable boundaries (say of the "zig-zag" type) on general grapheneic structures--thereby readily explaining novel features of different boundaries.

Ring currents in silicon tetramer (Si4, Si42+) and planar tetracoordinate carbon doped cluster Si4C2+: σ versus π aromaticity

We revisited the aromaticity of silicon tetramer Si4, Si42+ and isoelectronic four-membered rings without and with a planar tetracoordinate carbon dopant (Si4C2+). Electron localizability indicators and magnetic ring currents were used to probe bonding patterns. Comparison with Al42−, Si2Al2, Al4C2− and Si2Al2C was performed. The 14 (Si42+), 16 (Si4) and 18 (Si4C2+) valence electrons systems exhibit diatropic ring current, but this is determined by σ electrons. Electrons in π orbitals do not significantly take part in the diatropic magnetic response which determines aromaticity. These clusters can thus be regarded as σ-aromatic species and do not follow the classical Hückel rule.

Electronic Origin of Out‐of‐Plane Distortions in Porphyrins

AbstractPorphyrins are noninnocent ligands that facilitate redox processes in many biological reactions. Though the porphyrin dianion is planar and aromatic, in many instances, its skeleton exhibits a variety of out‐of‐plane (OOP) distortions, which are primarily attributed to steric factors. Nevertheless, these distortions are suspected to play a hidden role in their biochemical reactions, as the nature of the distortion is conserved for a specific functionality across species. The propensity of porphyrins to assist redox reactions remains mysterious, as oxidation and OOP distortions affect their aromaticity. Our quantum chemical modelling of the two‐electron oxidation of porphyrin reveals that there are definite electronic reasons behind OOP distortions. An extension of the frontier orbital model of Gouterman to include the occupied b1g, b2g and a1g (σ) molecular orbitals (MOs) is necessary to explain the nature and origin of OOP distortions. The distortions are the effect of the mixing of these σ‐type MOs with the π‐type a1u and a2u highest occupied molecular orbitals (HOMOs). These are further facilitated by the flexibility of the internal [16]annulene skeleton of the porphyrin framework. In the absence of transition metal ions, oxidation usually entails pronounced bond alternation along this internal cross owing to a1u/a2u mixing, which leads to the loss of aromaticity. However, this is accompanied by OOP distortions that help to retain the local aromaticity of the pyrrolic rings. Transition metal porphyrins with their energetically accessible d orbitals prefer OOP distortions over bond alternation and effectively conserve aromaticity. For late transition metal ions, the d8 electronic configuration, which is ideal for a square‐planar complex, itself shows a variety of OOP distortions that stabilize the corresponding oxidation state through the mixing of the b1g MO with the a2u MO. For octahedral complexes with d6 configuration of the central metal ion, a two‐electron oxidation is effectively supported by OOP distortions that result from the mixing of the b2g MO with the a2u MO. The a1u MO is usually less prone to mixing as it is concentrated far away from the central metal ion. Despite involving σ–π mixing, these OOP distortions conserve the aromaticity as shown by the computed chemical shifts of the optimized porphyrin systems. In addition to explaining the origin of the noninnocent nature of porphyrins, our results also provides a basis for the rational prediction and control of the OOP distortions to suite the desired biomimetic applications.

Classification SAR Modeling of Diverse Quinolone Compounds for Antimalarial Potency Against Plasmodium falciparum

Both a development of resistance to artemisinin monotherapy and lack of effective vaccine against malaria have created the urgent need for the development of new and efficient antimalarial agents. In this background, we have developed here a linear discriminant analysis (LDA) model and a few 3D-pharmacophore models for the classification of diverse quinolone compounds based on their antimalarial potency against Plasmodium falciparum. The discriminant model shows 70% correct classification for the test set compounds into higher active and lower active analogues. The best pharmacophore model (Hypo-1) with a correlation coefficient of 0.83 shows one hydrogen bond acceptor (HBA) and two ring aromatic (RA) features as the essential structural requirements for antimalarial activity against P falciparum. Both the models may act as in silico filters for a virtual screening and could be utilized for the selection of higher active molecules falling within the applicability of the models.

Substituent effects in trans-p,p'-disubstituted azobenzenes: X-ray structures at 100 K and DFT-calculated structures.

The crystal and molecular structures of two para-substituted azobenzenes with π-electron-donating -NEt2 and π-electron-withdrawing -COOEt groups are reported, along with the effects of the substituents on the aromaticity of the benzene ring. The deformation of the aromatic ring around the -NEt2 group in N,N,N',N'-tetraethyl-4,4'-(diazenediyl)dianiline, C20H28N4, (I), may be caused by steric hindrance and the π-electron-donating effects of the amine group. In this structure, one of the amine N atoms demonstrates clear sp(2)-hybridization and the other is slightly shifted from the plane of the surrounding atoms. The molecule of the second azobenzene, diethyl 4,4'-(diazenediyl)dibenzoate, C18H18N2O4, (II), lies on a crystallographic inversion centre. Its geometry is normal and comparable with homologous compounds. Density functional theory (DFT) calculations were performed to analyse the changes in the geometry of the studied compounds in the crystalline state and for the isolated molecules. The most significant changes are observed in the values of the N=N-C-C torsion angles, which for the isolated molecules are close to 0.0°. The HOMA (harmonic oscillator model of aromaticity) index, calculated for the benzene ring, demonstrates a slight decrease of the aromaticity in (I) and no substantial changes in (II).

Aromatics to bis-triquinane: a tandem oxidative dearomatization of bis-phenol, cycloaddition, photorearrangement and a rapid entry into carbocyclic framework of Xeromphalinone E

A novel approach for the synthesis of a bird-shaped bis-triquinane 3, a fascinating carbocyclic framework closely related to the skeleton of Xeromphalinone E 1 from readily available 2,6-dimethyl phenol 8 has been reported. The synthesis of bis-cyclohexadienones 6, 22a–e by oxidative acetylation of tetramethyl bisphenols 7, 20a–e has been investigated using two different reagents under varying reaction conditions. The cycloaddition of bis-cyclohexadienone 6 gives two carbocycles, bis-adduct 4b and mono-adduct 5d in a stereocontrolled manner. The photochemical sigmatropic 1,2-acyl shift in 4b furnished 3 and monotriquinane 9 linked with a 9-acetoxy-9-methyl-endo-tricyclo[5,2,2,02,6]undeca-4,10-diene-8-one system. Two different pentasubstituted phenols 13 and 14 were also isolated during an attempted oxa-di-π-methane (ODPM) rearrangement of mono-adduct 5d via aromatisation of the cyclohexadienone ring. The photochemical behaviour of bis-cyclohexadienones 6, 22a–e has also been investigated under UV irradiation and two different aromatized products were isolated for each bis-cyclohexadienone by migration and elimination of acetate groups.

Experimental and Theoretical Study of Aromaticity Effects in the Solid State Architecture on Squaric Acid Derivatives

In this manuscript, the aromaticity of the four-membered ring in squaric acid derivatives and, particularly, how it changes when it participates in noncovalent interactions are studied combining experimental observations and theoretical analysis using the nucleus independent chemical shift (NICS). Moreover, the ability of the squaric acid and its derivatives to establish hydrogen bonds, π–π stacking, and other π-interactions (anion−π, lone pair−π, and C–H/π) is related to the increase in the aromaticity of the ring. In addition, several squaric acid derivatives (benzamh)(sqah)·H2O (1), (pipropamh2)(sqa)·2H2O (2), (deamh)(deamsqa) (3), (phpetamh)(sqah)·(4), (amsqa)(sqa) (5), (and benzamh)(benzamsqa)·H2O (6) where benzam = benzylamine; sqah2 = squaric acid; deamsqah = diethylamidosquaric acid; pipropam = 3,3′-(piperazine-1,4-diyl)bis(propan-1-amine); deam = diethylamine phpetam = p-hydroxiphenylethylamine and benzamsqah = benzylamidosquaric acid) were synthesized and characterized by single crystal X-ray diffraction analyses.

Aromaticity As Driving Force for Bingel-Hirsch Derivatization of Endohedral Metallofullerenes

Functionalization of EMFs is mainly achieved via cycloaddition reactions, principally through Diels-Alder (DA), 1,3-dipolar and nucleophilic [2+1] Bingel-Hirsch (BH) additions. It has been shown that the strain induced by the inner metal cluster on the carbon structure plays an important role in determining the regioselectivity of the EMF exohedral functionalizations.1 Electronic effects are also essential due to the formal charge transfer from the metal cluster to the fullerene cage.2 In DA and 1,3-dipolar cases, the best criterion for chemical-reactivity predictions of EMFs is provided by a combination of short bond lengths, high pyramidalization angles, and appropriate shape of some of the LUMOs.1 However, there are some recent experimental examples of BH cycloadditions on non-IPR EMFs where the usually employed reactivity parameters are not able to reproduce the experimental observations.3 In this communication, we unveil that the driving force behind the BH addition on EMFs is the aromaticity. We have explored the complete BH reaction mechanism for Sc3N@D3h -C78 considering all non-equivalent addition sites. This system is the perfect scenario for investigating the BH addition as the encapsulated metal cluster cannot freely rotate and, therefore, the effect of the cluster on the BH reactivity is directly investigated. Our results clearly show that the BH addition is governed by the aromaticity of the fullerene rings.4 The aromaticity of the carbon cage of the first step intermediate of the reaction dictates the BH addition. Based on these observations, we have proposed some general aromaticity-based rules that correctly predict the most suitable BH addition sites for experimentally studied EMFs.5 [Figure 1 here] S. Osuna, M. Swart and M. Solà, J. Am. Chem. Soc., 2009, 131, 129.M. Garcia-Borràs, A. Romero-Rivera, S. Osuna, J. M. Luis, M. Swart and M. Solà, J. Chem. Theory Comput., 2012, 8, 1671.N. Alegret, M. N. Chaur, E. Santos, A. Rodríguez-Fortea, L. Echegoyen and J. M. Poblet, J. Org. Chem., 2010, 75, 8299.M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis, L. Echegoyen, and M. Solà, Chem. Commun. 2013, 49, 8767.M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis, L. Echegoyen, and M. Solà, in preparation.