Charge Delocalization Modes Research Articles

A computational study of SF5-substituted carbocations

The effect of the SF5 group as a substituent on various classes of carbocation was probed computationally employing DFT to examine geometrical changes, relative energies, and charge delocalization modes. Relative electron withdrawing power of the SF5 group was compared with CF3, NO2, CN, and SCF3 through isodesmic reactions. NPA charge densities were employed to gauge the influence of SF5 group on the charge delocalization modes in the carbocations.

Experimental NMR and DFT Studies of Persistent Carbocations Derived from Hetero-Polycyclic Aromatic Hydrocarbons Containing Oxygen Atom: Dibenzo[b,d]furan, Benzo[b]naphtho[1,2-d]furan, Benzo[b]naphtho[2,3-d]furan, Benzo[b]naphtho[2,1-d]furan, and Dinaphtho[2,1-b:1′,2′-d]furan

Abstract Persistent protonation carbocations generated from hetero-PAHs containing oxygen atoms in their aromatic rings, dibenzo[b,d]furan (5), benzo[b]naphtho[1,2-d]furan (6), benzo[b]naphtho[2,3-d]furan (7), benzo[b]naphtho[2,1-d]furan (8), and dinaphtho[2,1-b:1′,2′-d]furan (9), were directly observed by NMR measurements in superacid. Compound 5 was protonated mainly at C(2) in FSO3H–SbF5 (1:1) or (4:1)/SO2ClF, and 6, 8, and 9 were protonated exclusively at C(5) in CF3SO3H or FSO3H/SO2ClF, whereas 7 was protonated at C(6) and C(11) to give two species in FSO3H/SO2ClF. Surprisingly, compound 5 resists protonation in FSO3H/SO2ClF to show NMR spectra corresponding to that of the intact material. Positive charge delocalization mapping for carbocations based on experimental Δδ13C values indicates limited delocalization in these systems. The chemical shifts and charge delocalization modes derived by DFT calculations agreed with the experimental results.

Application of Electron Delocalization Indicators in the Study of Electrophilic Aromatic Substitution Reactions

Electron delocalization is a fundamental concept in chemistry. It is deeply rooted in many important chemical phenomena e.g. aromaticity, conjugation and the reactivity of a vast number of inorganic, organometallic and organic compounds. This review focuses on those theoretical studies in which electron delocalization indicators provide valuable insigths in the understanding of electrophilic aromatic substitutions. The considered approaches to deal with electron delocalization include primarily the quantum theory of atoms in molecules but also briefly the analysis of the electron localization function, the topography of the molecular electrostatic potential, the anisotropy of the induced current density and GIAO-derived charge delocalization modes. We go over the characterization of the electron delocalization in the most important intermediates of the electrophilic aromatic substitutions namely the Wheland intermediates and the π complexes formed by aromatic molecules and electrophiles. Then we discuss the relation between aromaticity and electrophilic aromatic substitutions. Finally, we give an account of the importance of the electron delocalization in the effect of the substituents on the regiochemistry and reactivity of an aromatic molecule towards an electrophilic attack. Besides reviewing the literature in an extensive way, it is our hope that this review will suggest directions of further progress in the field.

Oxidized metabolites from cyclopenta‐fused polycyclic aromatic hydrocarbons (CP‐PAHs). A DFT model study of their carbocations formed by epoxide ring opening

AbstractA density functional theory (DFT) study aimed at understanding structure–reactivity relationships in the oxidized metabolites of cyclopenta‐fused polycyclic aromatic hydrocarbons (CP‐PAHs) is reported. Epoxidation at various positions was examined in order to identify the most stable epoxide in each class of CP‐PAHs. Relative energies of the carbocations resulting from O‐protonation and epoxide ring opening were analyzed and compared, taking into account the available biological activity data on these compounds. Geometrical, electronic, and conformational issues were considered. Charge delocalization modes in the resulting carbocations were deduced via the natural population analysis (NPA)‐derived changes in charges. Computational results pointed to the importance of the unsaturated cyclopenta ring on the reactivity of these compounds. The reported bioactivity of this highly mutagenic/carcinogenic family of PAHs was observed to parallel their relative carbocation stabilities. A different behavior was observed in crowded non‐planar structures possessing a distorted aromatic system. A covalent adduct formed between a CP‐PAH epoxide and a purine base was computed inside a DNA fragment employing the ONIOM method. Copyright © 2010 John Wiley & Sons, Ltd.

Quantum Chemical Studies on Ultimate Carcinogenic Metabolites from Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants well known as mutagenic/carcinogenic agents. This review will discuss recent theoretical studies regarding the stability and reactivity of ultimate carcinogenic metabolites from PAHs, focusing on their diol epoxide and amine derivatives. Geometrical and electronic features will be analyzed in order to obtain structure-activity relationships. Charge delocalization modes (positive charge density distribution), substituent effects, and conformational aspects will be considered. Computed properties will be compared with the available biological activity data. Correlations between experimental mutagenic potencies reported in the literature and calculated reaction energies and electronic properties will be shown. Heteroaromatic compounds (aza-PAHs, thia-PAHs, and heteroaromatic amines) will also be examined. To model the important step of covalent adduct formation, calculation of the adducts resulting from bond formation between some of these electrophilic intermediates and nucleotide bases (guanine, cytosine) will be described.

Synthesis and Stable‐Ion Studies of Regioisomeric Acetylnitropyrenes and Nitropyrenyl Carbinols and GIAO‐DFT Study of Nitro Substituent Effects on α‐Pyrenyl Carbocations

AbstractSeveral regioisomeric acetylnitropyrenes were synthesized from isomeric acetylpyrenes by mild protic nitration. Nitration of 1‐acetylpyrene gave the 3‐, 6‐, and 8‐nitro derivatives (with 8‐nitro as the major isomer), from which the corresponding carbinols [NO2‐Py‐CH(OH)CH3; Py = pyrene] were synthesized. Isomeric 4‐acetylnitropyrenes and their corresponding carbinols were synthesized by starting from hexahydropyrene through nitration/aromatization/reduction or aromatization/nitration/reduction sequences. The molecular structures of 4‐acetyl‐3‐nitropyrene and 1‐(6‐nitropyren‐1‐yl)ethanol were established by X‐ray analysis. Tetrahydropyrene was the starting point for the synthesis of isomeric nitro‐2‐acetylpyrenes. Low‐temperature protonation of 1‐acetyl‐8‐nitropyrene, 4‐acetyl‐3‐nitropyrene, and 2‐acetyl‐6‐nitropyrene in FSO3H/SO2ClF or in FSO3H/SbF5 (1:1)/SO2ClF resulted in the formation of onium dications (by C=O and NO2 protonation). Charge delocalization (pyrenium ion character) in the carboxonium ions is strongly influenced by the position of the carboxonium group, with the 4‐acetyl‐3‐nitropyrene dication being the most delocalized. Superacid protonation of 1‐(3‐nitropyren‐4‐yl)ethanol gave a persistent onium dication rather than an α‐pyrenyl carbocation. With all other isolated nitropyrenyl carbinol isomers, low‐temperature protonation (with FSO3H/SO2ClF) led to polymerization within 5 min standing at dry‐ice–acetone temperature. For these cases, nitro substituent effects on the α‐pyrenyl carbocations were gauged by DFT and GIAO‐DFT studies. An interesting relationship between the computed nitro tilt angles and the GIAO‐derived charge delocalization modes was observed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Superacid‐Catalyzed Dimerization/Cyclization of Isopropenyl‐PAHs – Novel Pathways to PAH Dimers, Phenalenes and Their Stable Carbocations

AbstractThe isopropenyl derivatives of representative classes of polycyclic aromatic hydrocarbons (PAHs) having four and five fused‐ring systems, namely pyrene, chrysene, benzo[c]phenanthrene (BcPh), dibenzo[a,c]anthracene (benzo[f]tetraphene) and perylene, were synthesized by Wittig olefination from the corresponding acetyl‐PAHs. Under the influence of triflic acid (TfOH), the isopropenyl derivatives were converted to novel PAH dimers and/or phenalenes in a simple one‐pot procedure. A plausible mechanism for this process has been outlined, and the synthetic scope of this chemistry has been explored. Structural features in the PAH dimers were examined by DFT. As representative initial and final carbocation intermediates in the reaction sequence, stable carbocations derived from 3‐isopropenylperylene and from 4,6,6‐trimethyl‐6H‐dibenzo[a,kl]anthracene were generated and studied directly by NMR spectroscopy. The NMR characteristics and charge delocalization modes in the resulting benzylic carbocations are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Stable Ion NMR and GIAO-DFT Study of Novel Cations from 8,16-Dicyano[2.2]metacyclophanedienes and from Strategically Substituted/Benzannelated Dihydropyrenes: Charge-Induced Tropicity Modulation and π-Switching

The dicyanometacyclophanediene 1 is diprotonated at the cyano groups (1H2 2+) in various superacid media. Upon quenching, intact 1 and the ring-closed CPD 2 were obtained in a 3:2 or 3:1 ratio, depending on the superacid system. Compound 2 undergoes ring opening in the superacid to give the ipso-monoprotonated 2H+, which on quenching furnishes 1-cyanopyrene as a major product together with 2 and 1. The dication 3 2+, with strongly deshielded internal methyls, was generated from the epoxyannulene 3. Ketones 4-6 and ester 7 are O/C diprotonated to give paratropic carboxonium-annulenium dications (4H2 2+, 5H2 2+, 6H2 2+, and 7H2 2+, respectively). Ester 8 gives a trication by two-electron oxidation and O-protonation. Conjugated carboxylic acid 9 gives a mixture of two dications by CO and ring protonation. The dibromo derivatives 10 and 11 form carboxonium ions, whereas the monobromo derivative 12 is O/C diprotonated to give an oxonium-annulenium dication. Charge delocalization modes and tropicity in the resulting species are evaluated by NMR and GIAO-DFT. Facile formation of 2 from 1 in quenching experiments indicates that thermal closing can be achieved with the diprotonated dinitrile, without imposing skeletal rearrangement.

Electrophilic Chemistry of Thia-PAHs: Stable Carbocations (NMR and DFT), S-Alkylated Onium Salts, Model Electrophilic Substitutions (Nitration and Bromination), and Mutagenicity Assay

First examples of stable carbocations are reported from several classes of thia-PAHs with four fused rings, namely, benzo[b]naphtho[2,1-d]thiophene (1) and its 3-methoxy derivative (2), phenanthro[4,3-b]thiophene (3) and its 7-methoxy (4), 10-methoxy (5), and 9-methoxy (6) derivatives, phenanthro[3,4-b]thiophene (7) and its 7-methoxy (8) and 9-methoxy (9) derivatives, and 3-methoxybenzo[b]naphtha[1,2-d]thiophene (11). In several cases, the resulting carbocations were also studied by GIAO-DFT. Charge delocalization modes in the resulting carbocations were probed. A series of S-alkylated onium tetrafluoroborates, namely, 1Me+, 1Et+, 2Et+, and 7Me+ (from 1, 2, and 7), 10Me+ and 10Et+ (from benzo[b]naphtha[1,2-d]thiophene 10), 12Me+ and 12Et+ (from phenanthro[3,2-b][1]benzothiophene 12), 13Me+ (from 3-methoxyphenanthro[3,2-b]benzothiophene 13), 14Me+ (from phenanthro[4,3-b][1]benzothiophene 14), and 15Me+ (from 3-methoxyphenanthro[4,3-b][1]benzothiophene 15), were synthesized. PAH-sulfonium salts 1Me+, 1Et+, 10Me+, 10Et+, 12Me+, and 14Me+ proved to be efficient akylating agents toward model nitrogen nucleophile receptors (imidazole and azaindole). Facile transalkylation to model nucleophiles (including guanine) is also supported by favorable reaction energies computed by DFT. Ring opening energies in thia-PAH-epoxides from 1, 3, and 7 and charge delocalization modes in the resulting carbocations were also evaluated. The four-ring-fused thia-PAHs 1, 2, 3, 4, 5, 7, 8, and 11 are effectively nitrated under extremely mild conditions. Nitration regioselectivity corresponds closely to protonation under stable ion conditions. Bromination of 4 and 6 is also reported. Comparative mutagenicity assays (Ames test) were performed on 1 versus 1NO2, 5 versus 5NO2, and 11 versus 11NO2. Compound 5NO2 was found to be a potent direct acting mutagen.

Oxidized metabolites from benzo[a]pyrene, benzo[e]pyrene, and aza-benzo[a]pyrenes. A computational study of their carbocations formed by epoxide ring opening reactions

A DFT study aimed at understanding structure-reactivity relationships and fluorine substitution effects on carbocation stability in benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and aza-benzo[a]pyrene (aza-BaP) derivatives are reported. The relative energies of the resulting carbocations are examined and compared, taking into account the available biological activity data on these compounds. O-Protonation of the epoxides and diol epoxides leads to carbocation formation by barrierless processes. Charge delocalization modes in the resulting carbocations were deduced via NPA-derived changes in charges, and fluorine substitution effects were analyzed on the basis of charge density at different carbocation positions. Thus, fluorine substitution at sites bearing negative charge generated inductive destabilization of the carbocation, whereas a fluorine atom at a ring position which presented significant positive charge density produced a less pronounced destabilization due to fluorine p-pi back-bonding. Protonation reactions were also studied for the azaBaPs. In selected cases, the covalent adducts generated via bond formation with the exocyclic nitrogen of cytosine were computed and relative energies and geometries of the resulting adducts were examined.

Stable Ion and Electrophilic Substitution (Nitration and Bromination) Study of A‐Ring Substituted Phenanthrenes: Novel Carbocations and Substituted Derivatives; NMR, X‐ray Analysis, and Comparative DNA Binding

AbstractPersistent carbocations were generated from five A‐ring mono‐ and di‐substituted phenanthrenes [3‐OMe; 4‐OMe, 1,3‐bis(OMe), 2,4‐bis(OMe), and 1,3‐bis(Me)]. In all cases protonation occurs in the A‐ring, ortho/para relative to methoxy or methyl substituent(s). Complete NMR assignments of the resulting carbocations are reported and their charge delocalization modes are discussed. Mild nitration (with 20–50 % aqueous HNO3 at –10 °C or at room temp.) and bromination (NBS/MeCN/room temp.) of these substrates resulted in the synthesis of several novel mononitro‐/dinitro‐ as well as monobromo/dibromo derivatives, including those with nitro or bromo substituent in the bay‐region. Correspondence between the site of attack in low‐temperature protonation study and nitro substitution in ambient mild nitrations are examined. Complete NMR assignments for the new derivatives are reported as well as X‐ray structures for 2,4‐dimethoxy‐1‐nitro‐ and 1,3‐dimethyl‐4‐nitrophenanthrenes. A comparative DNA binding study with MCF cells on three of the synthesized mononitro and one dinitro derivative showed that 1,3‐dimethyl‐9‐nitro‐ (nitro at the meso position), 3‐methoxy‐4‐nitro‐ (nitro in bay‐region), and 1,3‐dimethoxy‐4,9‐dinitrophenanthrenes (nitro in both meso and bay‐regions) formed DNA adducts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A Computational Study of Carbocations from Oxidized Metabolites of Dibenzo[a,h]acridine and Their Fluorinated and Methylated Derivatives

In a model computational study aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability in aza-polycyclic aromatic hydrocarbons, the epoxides, diol epoxides, and the dihydrodiols of dibenzo[a,h]acridine (DB[a,h]ACR) were studied by density functional theory at the B3LYP/6-31G level. Bay region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (polarized continuum model method). Charge delocalization modes in the resulting carbocations were deduced by gauge-independent atomic orbitals (GIAO) NMR (based on Delta delta13C values) and via the natural population analysis (NPA)-derived changes in charges. Although the solvent decreases the exothermicity of the epoxide ring-opening reactions due to greater stabilization of the reactants, relative reactivity trends remain the same. Whereas fluorine substitution at ring positions bearing significant positive charge leads to carbocation stabilization by fluorine p-pi back-bonding, fluorine substitution at a ring position that presented negative charge density in the unsubstituted compound leads to inductive destabilization. Methylated derivatives exhibit less sensitivity to substituent effects as compared to the fluorinated analogues. A bay region methyl group produces structural distortion, and this deviation from planarity destabilizes the epoxide, favoring ring opening. Relative energies, changes in NPA charges, and GIAO NMR data in the resulting "benzylic" carbocations are examined collectively and discussed, taking into account the available biological activity data on these compounds.

Theoretical study of aza-polycyclic aromatic hydrocarbons (aza-PAHs), modelling carbocations from oxidized metabolites and their covalent adducts with representative nucleophiles

Protonation of the epoxides, diol epoxides, and dihydrodiols of benzo[h]quinoline (BhQ), benzo[f]quinoline (BfQ), phenanthrene (Phe), benzo[c]phenanthridine (BcPhen), and chrysene (Chry) were studied by DFT at the B3LYP/6-31G* level, and selected cases were calculated with the 6-31+G* diffuse-function augmented basis set for comparison purposes. Bay-region carbocations were formed from O-protonated epoxides via a barrierless processes. Relative carbocation stabilities were determined in the gas phase and with water as solvent (PCM method). The presence of a heteroatom changes the regioselectivity of epoxide ring opening, in some cases favoring non-bay-region carbocations. The epoxide ring opening mode is also greatly influenced by N-protonation. The dications resulting from initial N-protonation followed by epoxide protonation were also studied by DFT. Charge delocalization modes in the resulting mono- and dications were derived by GIAO-NMR (based on Delta delta13C values) and via the NPA-derived changes in charges. Relative aromaticity in different rings in the arenium ions was gauged by NICS. In representative cases, the covalent adducts (syn and anti) formed by reaction of the benzylic carbocations derived from diol epoxides and dihydrodiols with methoxide and methanethiolate anions were studied. Relative energies (in the gas phase and with water as solvent) and geometries of the adducts formed by quenching of the carbocations derived from BhQ and Phe-epoxides with guanine via the exocyclic amino group and via the N-7 were also investigated computationally. Although aqueous phase calculations change the energy for the addition reactions because of greater stabilization of the reactants, relative reactivity trends remain the same. The data are discussed, taking into account the available experimental results concerning the biological activity of these compounds.

Theoretical (DFT, GIAO–NMR, NICS) study of carbocations (M+H)+, dications (M2+) and dianions (M2−) from dihydro-dicyclopenta[ef,kl]heptalene (dihydro-azupyrene), dihydro-dicyclohepta[ed,gh]pentalene, and related bridged [14]annulenes

The annulenium ions of protonation, the two-electron oxidation dications, and the two-electron reduction dianions derived from dihydro- and dimethyldihydro derivatives (cis and trans) of dicyclopenta[ef,kl]heptalene (azupyrene) (1) and dicyclohepta[ed,gh]pentalene (2), which are the nonalternant isomers of pyrene, were studied by density functional theory (DFT) at the B3LYP/6-31G(d), 6-31+G(d,p), or 6-31++G(d,p) levels. Charge delocalization modes in the energetically most favored annulenium ions, as well as in the singlet and triplet dications and dianions, were assessed based on gauge-including atomic orbital (GIAO) Deltadelta](13)C values and via changes in natural population analysis (NPA) charges. Relative aromaticity/antiaromaticity in the annulenes were gauged via nucleus-independent chemical shift (NICS) and DeltaNICS. Annulenium ions of monoprotonation, the dications, and dianions derived from bismethano- and propanediylidene [14]annulenes were also studied by DFT for comparison with the cis-dihydro isomers derived from . Computed GIAO NMR data and the optimized geometries were compared with the experimental data when available, and the optimized geometries were compared with the X-ray data if known. A basis-set dependency study of the computed GIAO chemical shifts was also undertaken. The present DFT work represents the first detailed comparative theoretical study of charged annulenes derived from the dihydro derivatives of and .

超強酸中での[5]helicene誘導体の反応と発生するカルボカチオンの陽電荷分布

超強酸中での[5]helicene誘導体の反応と発生するカルボカチオンの陽電荷分布