(Trifluoromethoxy)Phenylboronic Acids: Structures,Properties, and Antibacterial Activity

Three isomers of (trifluoromethoxy)phenylboronic acids were studied in the context of their physicochemical, structural, antimicrobial and spectroscopic properties. They were characterized by ¹H, ¹³C, ¹¹B and ¹⁹F NMR spectroscopy. The acidity of all the isomers was evaluated by both spectrophotometric and potentiometric titrations. The introduction of the -OCF₃ group influences the acidity, depending, however, on the position of a substituent, with the ortho isomer being the least acidic. Molecular and crystal structures of ortho and para isomers were determined by the single crystal XRD method. Hydrogen bonded dimers are the basic structural motives of the investigated molecules in the solid state. In the case of the ortho isomer, intramolecular hydrogen bond with the -OCF₃ group is additionally formed, weaker, however, than that in the analogous -OCH₃ derivative, which has been determined by both X-Ray measurements as well as theoretical DFT calculations. Docking studies showed possible interactions of the investigated compounds with LeuRS of Escherichia coli. Finally, the antibacterial potency of studied boronic acids in vitro were evaluated against Escherichia coli and Bacillus cereus.     

Trapping of a cycloheptatetraene in the reaction of atomic carbon with phenol

Reaction of atomic carbon with phenol generates tropone in a reaction postulated to proceed via the hydroxycycloheptatetraenes, which rearrange to tropone. When the hydroxyphenylcarbenes are generated by the C atom deoxygenation of the corresponding aldehydes, the meta and para isomers produce tropone; the ortho isomer does not.     

Separating Para and Ortho Water

Water exists as two nuclear‐spin isomers, para and ortho, determined by the overall spin of its two hydrogen nuclei. For isolated water molecules, the conversion between these isomers is forbidden and they act as different molecular species. Yet, these species are not readily separated, and no pure para sample has been produced. Accordingly, little is known about their specific physical and chemical properties, conversion mechanisms, or interactions. The production of isolated samples of both spin isomers is demonstrated in pure beams of para and ortho water in their respective absolute ground state. These single‐quantum‐state samples are ideal targets for unraveling spin‐conversion mechanisms, for precision spectroscopy and fundamental symmetry‐breaking studies, and for spin‐enhanced applications, for example laboratory astrophysics and astrochemistry or hypersensitized NMR experiments.     

Identification of position isomers by energy‐resolved mass spectrometry

This study reports an energy‐resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals (^●OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by ^●OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision‐induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M ? H]^? towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M ? H]^? molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time‐consuming separation/purification methods along with the use of multi‐spectroscopic methods. Copyright © 2015 John Wiley & Sons, Ltd.     

Imaging the Bonds of Dehalogenated Benzene Radicals on Cu(111) and Au(111)

Dissociative adsorption of doubly substituted benzene molecules leads to formation of benzyne radicals. In this study, co‐adsorbed hydrogen molecules are used in scanning tunneling hydrogen microscopy to enhance the contrast of the meta‐ and the para‐isomers of these radicals on Cu(111) and Au(111). Up to three hydrogen molecules are attached to one radical. One hydrogen molecule reveals the orientation of the carbon ring and its adsorption site, allowing discrimination between the two radicals. Two hydrogen molecules reflect the bond picture of the carbon skeleton and reveals that adsorption on Cu(111) distorts the meta‐ isomer differently from its gas‐phase distortion. Three hydrogen molecules allow us to determine the bond picture of a minor species.     

Calorimetric study of ionization processes for nitro-substituted phenols in water-dimethylsulfoxide mixtures at 25°C

The ionization and solution enthalpies of the nitrophenol isomers were measured calorimetrically at 25°C in water-DMSO mixtures ranging from pure water up to 0.8 DMSO mole fraction.The different solvation values obtained for ortho-nitrophenol with respect to the meta and para isomers, were explained taking into account the electrostatic forces between the water molecules and the anions, as well as the intramolecular and intermolecular hydrogen bonds associated with the undissociated molecules.     

Effect of the structure of the <Emphasis Type="Italic">ortho</Emphasis>, <Emphasis Type="Italic">meta</Emphasis>, and <Emphasis Type="Italic">para</Emphasis> isomers of perhydroterphenyl on their reactivity in heterogeneous catalytic dehydrogenation

The kinetics of the dehydrogenation of the individual ortho, meta, and para isomers of perhydroterphenyl and their mixtures over a (3 wt % Pt)/C catalyst has been investigated in a flow reactor at 280–340°C. The rate of the isomerization of the stereoisomers of the initial substrate (perhydroterphenyl) and terphenyl dehydrogenation products has an effect on the hydrogen release kinetics. The highest reactivity in isomerization is shown by the ortho isomer. The largest amount of hydrogen (7.0 wt %) is released in the dehy-drogenation of perhydro-meta-terphenyl and perhydro-para-terphenyl, whose conversion at 320°C is 96%.     

Quantum Chemical Approach for Determining Degradation Pathways of Phenol by Electrical Discharge Plasmas

This study uses density functional theory (DFT) simulations to predict the main pathways by which hydroxyl (OH) radicals oxidize phenol into monohydroxylated products during an electrical discharge directly in or contacting water. The calculated activation energies and reaction rate constants indicate that phenol ring H abstraction is less likely to occur than OH addition, which will be the fastest in the ortho and para positions. The chain propagation with molecular oxygen of such formed ortho and para radicals will result in the production of hydroquinone and catechol, which are, concurrently, the most likely products of phenol degradation by OH radicals. Electron transfer reactions between dihydroxycyclohexadienyl radicals and plasma oxidative species are another important reaction mechanism which may be contributing significantly to the formation of products. Good agreement between computed kinetic and experimental data demonstrates the feasibility of applying DFT to investigate chemical reaction mechanisms.     

Alkali‐Metal Trichloroacetates for Dichloromethylenation of Fullerenes: Nucleophilic Addition‐Substitution Route

The first experimental evidence that fullerenes react with alkali‐metal trichloroacetates through a nucleophilic addition‐substitution route, yielding dichloromethylenefullerenes as the final products, is reported. The intermediates, C₆₀(CCl₃)^? and C₇₀(CCl₃)^? anions, have been isolated in their protonated forms as ortho‐C₆₀(CCl₃)H, as well as three ortho and one para isomer of C₇₀(CCl₃)H. The structures were unambiguously determined by means of ¹H, ¹³C, and ¹H–¹³C HMBC NMR spectroscopy along with UV/Vis spectroscopy. The observed regiochemistry was analyzed with the aid of quantum chemical calculations. Conversion of the protonated compounds into the [6,6]‐closed C_60/70(CCl₂) cycloadducts under basic conditions can be effected only for the ortho isomers, whereas para‐C₇₀(CCl₃)H decomposes back into pristine C₇₀.     

A new biologically active molecular scaffold: crystal structure of 7‐(3‐hydroxyphenyl)‐4‐methyl‐2H‐[1,2,4]triazolo[3,2‐c][1,2,4]triazole and selective antiproliferative activity of three isomeric triazolo–triazoles

A study of three isomeric compounds containing a phenolic moiety attached to the nitrogen‐rich triazolo–triazole bicycle is presented. In the three isomers, the phenolic OH group is in the ortho, meta and para positions. The crystal structure analysis of the meta isomer (C₁₀H₉N₅O) shows that the 2H‐tautomer is present in the crystal and that the molecule adopts a substantially planar geometry. However, the conformation found in the crystal is different compared to the monoprotonated cation of the same compound previously investigated in several salts. The packing of the meta isomer is driven by the formation of strong hydrogen bonds and shows the formation of infinite planar ribbons, parallel to a, formed around 2₁ crystallographic axes. The three isomers were tested against some cancer cell lines and also against normal cell lines. The ortho isomer shows a weak antiproliferative activity, the meta isomer shows significant antiproliferative activity against some cancer lines and no activity against healthy cell lines, and the para isomer is active against all the tested cell lines.     

Polymethylations of bis(cyanomethyl)benzenes

o-, m- and p-bis(cyanomethyl)benzene were reacted with various quantities of methyllithium and methyliodide. Di and tetra methylations can be easily obtained in the cases of the meta and para isomers. Di and tri methylations were obtained in the reactions of the ortho isomer. The product from tri methylation of the ortho isomer cyclizes under the reaction conditions to a 3-indanone derivative.     

ortho-Substituted 2-Phenyldihydroazulene Photoswitches: Enhancing the Lifetime of the Photoisomer by ortho-Aryl Interactions

Photochromic molecules are systems that undergo a photoisomerization to high-energy isomers and are attractive for the storage of solar energy in a closed-energy cycle, for example, in molecular solar thermal energy storage systems. One challenge is to control the discharge time of the high-energy isomer. Here, we show that different substituents in the ortho position of a phenyl ring at C-2 of dihydroazulene (DHA-Ph) significantly increase the half-life of the metastable vinylheptafulvene (VHF-Ph) photoisomer; thus, the energy-releasing VHF-to-DHA back-reaction rises from minutes to days in comparison to the corresponding para- and meta-substituted systems. Systems with two photochromic DHA-Ph units connected by a diacetylene bridge either at the para, meta and ortho positions and corresponding to a linear or to a cross-conjugated pathway between the two photochromes are also presented. Here, the ortho substitution was found to compromise the switching properties. Thus, irradiation of ortho-bridged DHA-DHA resulted in degradation, probably due to the proximity of the different functional groups that can give rise to side-reactions.     

The Loss of a hydroxyl group from the molecular ions of alkylnitrobenzenes

It is confirmed that the loss of HO˙ from the molecular ion of o-nitrotoluene involves exclusively a hydrogen from the methyl group. However, in higher homologues hydrogen atoms from non-benzylic sites are also implicated. With such compounds this fragmentation mode is shown not only by the ortho but, to a lesser extent, by the meta and para isomers as well. The proportion of the total ion current borne by the [M – 17]⁺ ion follows the order ortho > meta > para, which is attributed to substituent migration around the ring with a hydroxyl radical only being lost when the groups are on adjacent ring atoms. Other ions present in the spectra point to interaction between substituents to form a new heterocyclic ring.     

Natural abundance 17O NMR study of 2- and 4-substituted benzoyl chlorides

Natural abundance ¹⁷O NMR chemical shift data for 17 ortho and para benzoyl chlorides recorded in acetonitrile at 75°C are reported. ¹⁷O NMR data for the para substituted benzoyl chlorides are correlated with ¹⁷O NMR data for similarly substituted acetophenones and methyl benzoates. The ¹⁷O NMR signals for ortho isomers are downfield (ca 30 ppm) from their para isomers; the downfield shifts are consistent with torsion angle change. The ¹⁷O NMR data for the para isomers gave good correlations with σ⁺ constants and with dual substituent parameters (DSP).     

Regiospecific oxidation of polycyclic aromatic phenols to quinones by hypervalent iodine reagents

The hypervalent iodine reagents o-iodoxybenzoic acid (IBX) and bis(trifluoro-acetoxy)iodobenzene (BTI) are shown to be general reagents for regio-controlled oxidation of polycyclic aromatic phenols (PAPs) to specific isomers (ortho, para, or remote) of polycyclic aromatic quinones (PAQs). The oxidations of a series of PAPs with IBX take place under mild conditions to furnish the corresponding ortho-PAQs. In contrast, oxidations of the same series of PAPs with BTI exhibit variable regiospecificity, affording para-PAQs where structurally feasible and ortho-PAQs or remote PAQ isomers in other cases. The structures of the specific PAQ isomers formed are predictable on the basis of the inherent regioselectivities of the hypervalent iodine reagents in combination with the structural requirements of the phenol precursors. IBX and BTI are recommended as the preferred reagents for regio-controlled oxidation of PAPs to PAQs.     

Three isomeric bis(methoxycarbonyl)[2.2]paracyclophanes

The title isomers 4,16‐ (pseudo‐ortho), 4,15‐ (pseudo‐gem) and 4,12‐bis­(methoxy­carbonyl)[2.2]­para­cyclo­phane (pseudo‐para), C₂₀H₂₀O₄, all show the typical structural features of [2.2]­para­cyclo­phanes (flattened boat conformation of the rings, lengthened single bonds in the bridges and narrow ring angles at the bridgehead atoms). The 4,12‐isomer displays crystallographic inversion symmetry. The carbonyl groups adopt a conformation in which they are directed away from the ring systems towards the nearest bridge; the corresponding angle at the ring substituent atom is widened. Crystal packing involves C—H?π interactions for the 4,15‐isomer and weak C—H?O hydrogen bonds for the other two isomers.     

Temperature effect on the single and double hydrogen atom transfer reactions in o-, m-and p-toluic acid butyl esters

The temperature effect on the single and double hydrogen atom transfer reactions in o-, m- and p-toluic acid n-butyl esters and isobutyl esters has been investigated. For the meta and para isomers, the abundance of the m/z 137 ion [C₈H₉O₂]⁺ generated by a double hydrogen atom transfer reaction increases relative to the m/z 136 ion [C₈H₈O₂]⁺˙ generated by a single hydrogen atom transfer reaction upon lowering the temperature of the ionization chamber. On the other hand, the ratio of the peak abundances [137]⁺/[136]⁺ for the ortho isomers is nearly constant when the temperature is changed. It is shown that this is due to the difference between the appearance energies of the m/z 136 and m/z 137 ions.     

A DFT study of proton transfers for the reaction of phenol and hydroxyl radical leading to dihydroxybenzene and H2O in the water cluster

Reactions of phenol and hydroxyl radical were studied under the aqueous environment to investigate the antioxidant characters of phenolic compounds. M06‐2X/6‐311 + G(d,p) calculations were carried out, where proton transfers via water molecules were examined carefully. Stepwise paths from phenol + OH^• + (H₂O)_n (n = 3, 7, and 12) to the phenoxyl radical (Ph O^•) via dihydroxycyclohexadienyl radicals (ipso, ortho, meta, and para OH‐adducts) were obtained. In those paths, the water dimer was computed to participate in the bond interchange along hydrogen bonds. The concerted path corresponding to the hydrogen atom transfer (HAT, apparently Ph OH + OH^• → Ph O^• + H₂O) was found. In the path, the hydroxyl radical located on the ipso carbon undergoes the charge transfer to prompt the proton (not hydrogen) transfer. While the present new mechanism is similar to the sequential proton loss electron transfer (SPLET) one, the former is of the concerted character. Tautomerization reactions of ortho or para (OH)C₆H₅=O + (H₂O)_n → C₆H₄(OH)₂(H₂O)_n were traced with n = 2, 3, 4, and 14. The n = 3 (and n = 14) model of ortho and para was calculated to be most likely by the strain‐less hydrogen‐bond circuit.     

Combining UV photodissociation action spectroscopy with electron transfer dissociation for structure analysis of gas‐phase peptide cation‐radicals

We report the first example of using ultraviolet (UV) photodissociation action spectroscopy for the investigation of gas‐phase peptide cation‐radicals produced by electron transfer dissociation. z ‐Type fragment ions ^●Gly‐Gly‐Lys⁺, coordinated to 18‐crown‐6‐ether (CE), are generated, selected by mass and photodissociated in the 200–400 nm region. The UVPD action spectra indicate the presence of valence‐bond isomers differing in the position of the C_α radical defect, (α‐Gly)‐Gly‐Lys⁺(CE), Gly‐(α‐Gly)‐Lys⁺(CE) and Gly‐Gly‐(α‐Lys⁺)(CE). The isomers are readily distinguishable by UV absorption spectra obtained by time‐dependent density functional theory (TD‐DFT) calculations. In contrast, conformational isomers of these radical types are calculated to have similar UV spectra. UV photodissociation action spectroscopy represents a new tool for the investigation of transient intermediates of ion‐electron reactions. Specifically, z ‐type cation radicals are shown to undergo spontaneous hydrogen atom migrations upon electron transfer dissociation. Copyright © 2015 John Wiley & Sons, Ltd.     

Absolute configuration assignment of ortho,meta, or para isomers by mass spectrometry

A general method based solely on mass spectrometric techniques for the absolute configuration assignment of ortho, meta, or para isomers of acyl nitrobenzenes and derivatives is described. Instead of comparing the mass spectra of the three intact molecules of each positional isomer and investigating each one of the many sets of positional isomers, the method generalizes the effort by performing structural analysis on configurationally diagnostic fragment ions that are common for a given class of compounds. These ions must therefore retain the positional information of the parent molecules and be unequivocally distinguished. Nitrobenzoyl cations are common and stable fragment ions of most acyl nitrobenzenes and derivatives retaining the respective ortho, meta, or para configuration of the precursor molecules. The different NO₂ and CO⁺ ring alignments profoundly influence their collision-induced dissociation and bimolecular reactivity, and the isomeric 2-, 3-, and 4-nitrobenzoyl cations are found to be unequivocally distinguished using both approaches. Absolute ortho, meta, or para positional assignment by tandem MS of every isomeric molecule of the acyl nitrobenzene class and derivatives forming detectable amounts of any of those diagnostic nitrobenzoyl cations is, therefore, possible. The ability to perform absolute (non-comparative) configuration assignment using such diagnostic ions is exemplified for a single test molecule of (2R)-(−)-2-methylglycidyl 4-nitrobenzoate. The general application of this absolute MS-only method for other classes of positional isomers is discussed.