Correlations of ion structure with multiple fragmentation pathways arising from collision‐induced dissociations of selected α‐hydroxycarboxylic acid anions

Under conditions of collision‐induced dissociation (CID), anions of α‐hydroxycarboxylic acids usually fragment to yield the distinctive hydroxycarbonyl anion (m/z 45) and/or the complementary product anion formed by neutral loss of formic acid (46 u). Further support for the known two‐step mechanism, involving an ion‐neutral complex for the formation of the hydroxycarbonyl anion from the carboxyl group, is herein provided by tandem mass spectrometric results and density functional theory computations on the glycolate, lactate and 3‐phenyllactate ions. A fourth, structurally related α‐hydroxycarboxylate ion, obtained by deprotonation of mandelic acid, showed only loss of carbon dioxide upon CID. Density functional theory computations on the mandelate ion indicated that similar energy inputs were required for a direct, phenyl‐assisted decarboxylation and a postulated novel rearrangement to a carbonate ester, which yielded the benzyl oxide ion upon loss of CO₂. Rearrangement of the glycolate ion led to expulsion of carbon monoxide, whereas the 3‐phenyllactate ion showed the loss of water and formation of the benzyl anion and the benzyl radical as competing processes. The fragmentation pathways proposed for lactate and 3‐phenyllactate are supported by isotopic labeling. The relative computed energies of saddle points and product ions for all proposed fragmentation pathways are consistent with the energies supplied during CID experiments and the observed relative intensities of product ions. The diverse reaction pathways characterized for this set of four α‐hydroxycarboxylate ions demonstrate that it is crucial to understand the effects of structural variations when attempting to predict the gas‐phase reactivity and CID spectra of carboxylate ions. Copyright © 2013 John Wiley & Sons, Ltd.     

Fragmentation pathways of deprotonated amide‐sulfonamide CXCR4 inhibitors investigated by ESI‐IT‐MSn,ESI‐Q‐TOF‐MS/MS and DFT calculations

Amide‐sulfonamides provide a potent anti‐inflammatory scaffold targeting the CXCR4 receptor. A series of novel amide‐sulfonamide derivatives were investigated for their gas‐phase fragmentation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time‐of‐flight mass spectrometry in negative ion mode. Upon collision‐induced dissociation (CID), deprotonated amide‐sulfonamides mainly underwent either an elimination of the amine to form the sulfonyl anion and amide anion or a benzoylamide derivative to provide sulfonamide anion bearing respective substituent groups. Based on the characteristic fragment ions and the deuterium–hydrogen exchange experiments, three possible fragmentation mechanisms corresponding to ion‐neutral complexes including [sulfonyl anion/amine] complex ( INC‐1 ), [sulfonamide anion/benzoylamide derivative] complex ( INC‐2 ) and [amide anion/sulfonamide] complex ( INC‐3 ), respectively, were proposed. These three ion‐neutral complexes might be produced by the cleavages of S–N and C–N bond from the amide‐sulfonamides, which generated the sulfonyl anion (Route 1), sulfonamide anion (Route 2) and the amide anion (Route 3). DFT calculations suggested that Route 1, which generated the sulfonyl anion (ion c ) is more favorable. In addition, the elimination of SO₂ through a three‐membered‐ring transition state followed by the formation of C–N was observed for all the amide‐sulfonamides.     

Characterization of multiple fragmentation pathways initiated by collision‐induced dissociation of multifunctional anions formed by deprotonation of 2‐nitrobenzenesulfonylglycine

The correlation of anion structure with the fragmentation behavior of deprotonated nitrobenzenesulfonylamino acids was investigated using tandem mass spectrometry, isotopic labeling and computational methods. Four distinct fragmentation pathways resulting from the collision‐induced dissociation (CID) of deprotonated 2‐nitrobenzenesulfonylglycine (NsGly) were characterized. The unusual loss of the aryl nitro substituent as HONO was the lowest energy process. Subsequent successive losses of CO, HCN and SO₂ indicated that an ortho cyclization reaction had accompanied loss of HONO. Other pathways involving rearrangement of the ionized sulfonamide group, dual bond cleavage and intramolecular nucleophilic displacement were proposed to account for the formation of phenoxide, arylsulfinate and arylsulfonamide product ions at higher collision energies. The four distinct fragmentation pathways were consistent with precursor–product relationships established by CID experiments, isotopic labeling results and the formation of analogous product ions from 2,4‐dinitrobenzenesulfonylglycine and the Ns derivatives of alanine and 2‐aminoisobutyric acid. The computations confirmed a low barrier for ortho cyclization with loss of HONO and feasible energetics for each reaction step in the four pathways. Computations also indicated that three of the fragmentation pathways started from NsGly ionized at the carboxyl group. Overall, the pathways identified for the fragmentation of the NsGly anion differed from processes reported for anions containing a single functional group, demonstrating the importance of functional group interactions in the fragmentation pathways of multifunctional anions. Copyright © 2014 John Wiley & Sons, Ltd.     

ToF‐SIMS and computation analysis: Fragmentation mechanisms of polystyrene,polystyrene‐d5, and polypentafluorostyrene

We studied the time‐of‐flight secondary ion mass spectrometry fragmentation mechanisms of polystyrenes—phenyl‐fluorinated polystyrene (5FPS), phenyl‐deuterated polystyrene (5DPS), and hydrogenated polystyrene (PS). From the positive ion spectra of 5FPS, we identified some characteristic molecular ion structures with isomeric geometries such as benzylic, benzocyclobutene, benzocyclopentene, cyclopentane, and tropylium systems. These structures were evaluated by the B3LYP‐D/jun‐cc‐pVDZ computation method. The intensities of the C₇H₂F₅⁺ (m/z = 181), CyPent‐C₉H₃F₄⁺ (m/z = 187), CyPent‐C₉H₄F₅⁺ (m/z = 207), and CyPent‐C₉H₂F₅⁺ (m/z = 205) ions were enhanced by resonance stabilization. The positive fluorinated ions from 5FPS tended to rearrange and produce fewer fluorine‐containing molecular ions through the loss of F (m/z = 19), CF (m/z = 31), and CF₂ (m/z = 50) ion fragments. Consequently, the fluorine‐containing polycyclic aromatic ions had much lower intensities than their hydrocarbon counterparts. We propose the fragmentation mechanisms for the formation of C₅H₅⁺, C₆H₅⁺, and C₇H₇⁺ ion fragments, substantiated with detailed analyses of the negative ion spectra. These ions were created through elimination of a pentafluoro‐phenyl anion (C₆F₅⁻) and H⁺, followed by a 1‐electron‐transfer process and then cyclization of the newly generated polyene with carbon‐carbon bond formation. The pendant groups with elements of different electronegativities exerted strong influences on the intensities and fragmentation processes of their corresponding ions.     

9‐Benzylidene‐9H‐fluorene Derivatives Linked to Monoaza‐15‐crown‐5: Synthesis and Metal Ion Sensing

Two kinds of novel styryl chemosensory 2‐FMNC and 3‐FMNC, were designed and synthesized by an apporiate introduction of 9‐benzylidene‐9H‐fluorene group as fluorophore with the aim at avoiding photoisomerisation. These 9‐benzylidene‐9H‐fluorene derivatives showed the similar selectivity and sensitivity upon addition of metal ions. The sensitivity of FMNC to alkaline earth metal ions was Ba²⁺>Sr²⁺>Ca²⁺≈Mg²⁺.     

Prompt and Slow Electron‐Detachment‐Dissociation/Electron‐Photodetachment‐Dissociation of a 21‐Mer Peptide

Electron detachment dissociation (EDD) and electron photodetachment dissociation (EPD) are relatively new dissociation methods that involve electron detachment followed by radical‐driven dissociation from multiply deprotonated species. EDD yields prompt dissociation whereas only electron detachment is obtained by EPD; subsequent vibrational activation of the charge‐reduced radical anion is required to obtain the product ions. Herein, the fragmentation patterns that were obtained by EDD and by vibrational activation of the charge‐reduced radical anions that were produced through EDD or EPD (activated‐EDD and activated‐EPD) were compared. The observed differences were related to the dissociation kinetics and/or the contribution of electron‐induced dissociation (EID). Time‐resolved double‐resonance experiments were performed to measure the dissociation rate constants of the EDD product ions. Differences in the formation kinetics were revealed between the classical EDD/EPD ′a^._i/′′x_j complementary ions and some ′a^._i/c_i/′′′z^._j product ions, which were produced with slower dissociation rate constants, owing to the presence of specific neighbouring side chains. A new fragmentation pathway is proposed for the formation of the slow‐kinetics ′a^._i ions.     

两类三组份反应产物：1,3-恶嗪及嘧啶-2-酮类化合物的质谱学行为研究

电喷雾质谱被应用于分辨2-氨基-1,3-恶嗪及六氢化-4-苯基-吡喃[2,3-d]嘧啶-2-酮的杂环结构。两类化合物均为三组份反应的产物,且其杂环的结构很难用NMR判断。实验首次系统研究了两类化合物的质谱学行为（包括氘代实验和高分辨质谱研究）,发现前者在CID实验中丢失CH2N2和HCNO,而后者为直接丢失尿素。这些特征丢失为该类衍生物的结构判断,尤其是高通量的合成产物分析提供了重要的依据。     

Synthesis and Properties of 2‐Phenylbenzoxazole‐Based Luminophores for in situ Photopolymerized Liquid‐Crystal Films

We report the synthesis of a series of blue‐emitting 2‐phenylbenzoxazoles (PBOs) substituted at either the 5‐ or 6‐position of the benzoxazole ring and the para‐position of the phenyl substituent. The thermal and optical properties of the materials can be rationalized in terms of the position of the substituent at the benzoxazole moiety and the electron‐withdrawing or electron‐donating character of the substituents. From the results, we conclude that the combination of an electron‐donating substituent at the benzoxazole fragment and an electron‐withdrawing one at the phenyl fragment has a more marked effect on the electronic properties of the aromatic PBO core than other possibilities. This particular combination gives luminophores that are suitable for optical applications on the basis of their high emission efficiency and photostability. In view of that, oriented films were prepared by in situ polymerization of a mixture of a liquid crystalline direactive matrix containing 5% (w/w) of the luminophore. The films exhibit linearly polarized emission.     

Solvent‐ and concentration‐sensitive fluorescence of 2‐(3,4,5,6‐tetrafluoro‐2‐hydroxyphenyl)benzoxazole

2‐(3,4,5,6‐Tetrafluoro‐2‐hydroxyphenyl)benzoxazole ( 2 ) emits the long wavelength fluorescence around 500 nm in nonpolar solvent via the intramolecular proton transfer process in the excited state of 2 (enol‐form) and also emits the intermediate wavelength fluorescence around 440 nm in polar solvent, which is assumed to originate from the excited state of 2 (anion). The ease of formation of 2 (anion), compared to 2‐(2‐hydroxyphenyl)benzoxazole ( 1 ), is explained by the strongly inductive fluorine atoms. In a solvent with the intermediate polarity, 2 emits both fluorescences and their relative intensity is dependent on the concentration of 2 , which is supposed to be caused by the high sensitivity of the intermediate wavelength emission to the concentration quenching.     

Stereoselective synthesis of 1,4,2‐oxazaphosphorines as precursors of chiral α‐aminophosphonic acids by intramolecular heterocyclization of β‐aldiminoalkylphosphites

The intramolecular version of nucleophilic additon of phosphites to imines was carried out for the first time taking as an example β‐aldiminoalkylphosphites, formed from chlorophosphites and β‐aldiminoalcohols [N‐(benzylidene)‐2‐aminoethanol and R‐(+)‐N‐(benzylidene)‐2‐aminobutanol‐1]. In these reactions, stereoisomeric 1,4,2‐oxazaphosphorines were obtained in good yields. R‐(+)‐N‐(benzylidene)‐2‐aminobutanol‐1 being used as a precursor, nucleophilic attack by P(III) atom on electrophilic C atom of the CN group proceeds stereospecifically with participation of only re‐face of the two possible diastereotopic faces of the imine double bond to give the epimeric at phosphorus (3R,5R)‐2‐(β‐chloroethyl)‐2‐oxo‐3‐phenyl‐5‐ethyl‐1,4,2‐oxazaphosphorines as precursors of nonracemic α‐aminophosphonic acids. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:56–61, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10054     

Photolysis of Some N‐Arylbenzamidoximes in Acetonitrile

The photolysis of five N‐arylbenzamidoxime derivatives I‐V in dry acetonitrile gives rise to anilides 8 and benzimidazoles 1 as the major products in addition to benzonitrile 4 , arylamines 5 , benzoic acid 6 , and 2‐phenyl benzoxazoles 7 . In the presence of naphthalene, I gave α‐ and β‐naphthols 2 and 3 beside the previous products. The isolated products have been interpreted in the terms of a free radical mechanism involving the homolysis of N‐O and/or C‐N bonds. This photodegradation process can be considered as an alternative method for the synthesis of anilide, benzimidazole and benzoxazole derivatives in addition to other organic compounds.     

Investigation of c ions formed by N‐terminally charged peptides upon collision‐induced dissociation

Peptide fragments such as b and y sequence ions generated upon low‐energy collision‐induced dissociation have been routinely used for tandem mass spectrometry (MS/MS)‐based peptide/protein identification. The underlying formation mechanisms have been studied extensively and described within the literature. As a result, the ‘mobile proton model’ and ‘pathways in competition model’ have been built to interpret a majority of peptide fragmentation behavior. However, unusual peptide fragments which involve unfamiliar fragmentation pathways or various rearrangement reactions occasionally appear in MS/MS spectra, resulting in confused MS/MS interpretations. In this work, a series of unfamiliar c ions are detected in MS/MS spectra of the model peptides having an N‐terminal Arg or deuterohemin group upon low‐energy collision‐induced dissociation process. Both the protonated Arg and deuterohemin group play an important role in retention of a positive charge at the N‐terminus that is remote from the cleavage sites. According to previous reports and our studies involving amino acid substitutions and hydrogen–deuterium exchange, we propose a McLafferty‐type rearrangement via charge‐remote fragmentation as the potential mechanism to explain the formation of c ions from precursor peptide ions or unconventional b ions. Density functional theory calculations are also employed in order to elucidate the proposed fragmentation mechanisms. Copyright © 2016 John Wiley & Sons, Ltd.     

Chloride‐Selective Electrodes Based on “Two‐Wall” Aryl‐Extended Calix[4]Pyrroles: Combining Hydrogen Bonds and Anion–π Interactions to Achieve Optimum Performance

The performance of chloride‐selective electrodes based on “two‐wall” aryl‐extended calix[4]pyrroles and multiwall carbon nanotubes is presented. The calix[4]pyrrole receptors bear two phenyl groups at opposite meso‐positions. When the meso‐phenyl groups are decorated with strong electron‐withdrawing substituents, attractive anion–π interactions may exist between the receptor’s aromatic walls and the sandwiched anion. These anion–π interactions are shown to significantly affect the selectivity of the electrodes. Calix[4]pyrrole, bearing a p‐nitro withdrawing group on each of the meso‐phenyl rings, afforded sensors that display anti‐Hofmeister behavior against the lipophilic salicylate and nitrate anions. Based on the experimental data, a series of principles that help in predicting the suitability of synthetic receptors for use as anion‐specific ionophores is discussed. Finally, the sensors deliver excellent results in the direct detection of chloride in bodily fluids.     

The investigation of proton transfer and fluorescence‐sensing mechanisms of [2‐(2‐hydroxy‐phenyl)‐1H‐benzoimidazol‐5‐yl]‐phenyl‐methanone

Given the tremendous potential of fluorescence sensors in recent years, in this present work, we theoretically explore a novel fluorescence chemosensor [2‐(2‐Hydroxy‐phenyl)‐1H‐benzoimidazol‐5‐yl]‐phenyl‐methanone (HBPM) about its excited state behaviors and probe‐response mechanism. Using density functional theory (DFT) and time‐dependent density functional theory (TDDFT) methods, we explore the S₀‐state and S₁‐state hydrogen bond dynamical behaviors and confirm that the strengthening intramolecular hydrogen bond in the S₁ state may promote the excited state intramolecular proton transfer (ESIPT) reaction. In view of the photoexcitation process, we find that the charge redistribution around the hydroxyl moiety plays important roles in providing driving force for ESIPT. And the constructed potential energy curves further verify that the ESIPT process of HBPM should be ultrafast. That is the reason why the normal HBPM fluorescence cannot be detected in previous experiment. Furthermore, with the addition of fluoride anions, the exothermal deprotonation process occurs spontaneously along with the intermolecular hydrogen bond O–H?F. It reveals the uniqueness of detecting fluoride anions using HBPM molecules. As a whole, the fluoride anions inhibit the initial ESIPT process of HBPM, which results in different fluorescence behaviors. This work presents the clear ESIPT process and fluoride anion‐sensing mechanism of a novel HBPM chemosensor.     

Chemoselectivity in the Reaction of 2‐Diazo‐3‐oxo‐3‐phenylpropanal with Aldehydes and Ketones

The chemoselectivity in the reaction of 2‐diazo‐3‐oxo‐3‐phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et₃N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron‐donating substituents and cyclic ketones under formation of 6‐phenyl‐4H‐1,3‐dioxin‐4‐one derivatives. However, it reacts with aromatic aldehydes with electron‐withdrawing substituents to yield 1,3‐diaryl‐3‐hydroxypropan‐1‐ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron‐donating substituents. A mechanism for the formation of 1,3‐diaryl‐3‐hydroxypropan‐1‐ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N,N′‐dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS₂. Only with N,N′‐dialkylcarbodiimines, the expected cycloaddition took place.     

Multiple N—H...NC,C—H...NC and nitrile...π interactions in 4,4′‐bipyridine‐1,1′‐diium bis(1,1,3,3‐tetracyano‐2‐ethoxypropenide): structure determination and DFT calculations of anion...π cation interaction energies

Polynitrile anions are important in both coordination chemistry and molecular materials chemistry, and are interesting for their extensive electronic delocalization. The title compound crystallizes with two symmetry‐independent half 4,4′‐bipyridine‐1,1′‐diium (bpyH₂²⁺) cations and two symmetry‐independent 1,1,3,3‐tetracyano‐2‐ethoxypropenide (tcnoet⁻) anions in the asymmetric unit. One of the bpyH₂²⁺ ions is located on a crystallographic twofold rotation axis (canted pyridine rings) and the other is located on a crystallographic inversion center (coplanar pyridine rings). The ethyl group of one of the tcnoet⁻ anions is disordered over two sites with equal populations. The extended structure exhibits two separate N—H...NC hydrogen‐bonding motifs, which result in a sheet structure parallel to (010), and weak C—H...NC hydrogen bonds form joined rings. Two types of multicenter CN...π interactions are observed between the bpyH₂²⁺ rings and tcnoet⁻ anions. An additonal CN...π interaction between adjacent tcnoet⁻ anions is observed. Using density functional theory, the calculated attractive energy between cation and anion pairs in the tcnoet⁻...π(bipyridinediium) interactions were found to be 557 and 612 kJ mol⁻¹ for coplanar and canted bpyH₂²⁺ cations, respectively.     

Solid‐State Binding Studies of Group 2 Metal Ions with 12‐Crown‐4

The mode of co‐ordination of 12‐crown‐4 with the heavier group(II) ions Ca²⁺, Sr²⁺ and Ba²⁺ has been studied. Size limitations of the 12‐crown‐4 ligand enforced co‐ordinated metal ions to reside above the macrocyclic plane, with the remaining co‐ordination sphere occupied by water molecules and/or counter anions, or a second crown ether ligand to form a sandwich type species. Variation of the anion, by virtue of its co‐ordinating ability, affects the structural outcome.     

Fatty Acid Carboxylate‐ and Anionic Surfactant‐Controlled Delivery Systems That Use Mesoporous Silica Supports

We report the preparation of a MCM‐41 mesoporous material that contains the dye [Ru(bipy)₃]Cl₂ (bipy=bipyridine) inside the mesopores and functionalised with suitable binding groups at the entrance of the pores. Solids S1 – S3 were obtained by the reaction of the mesoporous material with N‐methyl‐N′‐propyltrimethoxysilylimidazolium chloride, N‐phenyl‐N′‐[3‐(trimethoxysilyl)propyl]thiourea, or N‐phenyl‐N′‐[3‐(trimethoxysilyl)propyl]urea, respectively. A study of the dye delivery of these systems in buffered water (pH 7.0, 2‐[4‐(2‐hydroxyethyl)piperazin‐1‐yl]ethanesulfonic acid (HEPES), 10^?3 mol dm^?3) in the presence of a family of carboxylate ions was carried out. In the interaction of the anions with the surface of the solids, the response depends on the characteristics of the binding groups (i.e., imidazolium, urea and thiourea) at the pore outlets and their specific interaction with the corresponding anion. The interaction of long‐chain carboxylate ions with the binding sites at the surface of the solids resulted in a remarkable inhibition of the delivery of the dye. This inhibition was observed clearly for the dodecanoate anion, whereas the octanoate, decanoate, cholate, deoxycholate, glycodeoxycholate and taurocholate anions induced a certain pore blockage that varied according to the solid studied. The interaction of smaller anions, such as acetate, butanoate, hexanoate and octanoate, with the solids had no effect on the dye release process. The possible use of the gating system for the chromo‐fluorogenic detection of anionic surfactants through selective dye delivery inhibition was also explored. Molecular dynamic simulations that use force‐field methods have been made to theoretically study the capping carboxylate mechanism. The calculations are in agreement with the experimental results, thus allowing a representation of the dye delivery inhibition in the presence of long‐chain carboxylate ions.     

Collision‐induced dissociation mass spectra of glucosinolate anions

Collision‐induced dissociation (CID) mass spectra of differently substituted glucosinolates were investigated under negative‐ion mode. Data obtained from several glucosinolates and their isotopologues (³⁴S and ²H) revealed that many peaks observed are independent of the nature of the substituent group. For example, all investigated glucosinolate anions fragment to produce a product ion observed at m/z 195 for the thioglucose anion, which further dissociates via an ion/neutral complex to give two peaks at m/z 75 and 119. The other product ions observed at m/z 80, 96 and 97 are characteristic for the sulfate moiety. The peaks at m/z 259 and 275 have been attributed previously to glucose 1‐sulfate anion and 1‐thioglucose 2‐sulfate anion, respectively. However, based on our tandem mass spectrometric experiments, we propose that the peak at m/z 275 represents the glucose 1‐thiosulfate anion. In addition to the common peaks, the spectrum of phenyl glucosinolate (β‐D ‐Glucopyranose, 1‐thio‐, 1‐[N‐(sulfooxy)benzenecarboximidate] shows a substituent‐group‐specific peak at m/z 152 for C₆H₅‐C(?NOH)S^?, the CID spectrum of which was indistinguishable from that of the anion of synthetic benzothiohydroxamic acid. Similarly, the m/z 201 peak in the spectrum of phenyl glucosinolate was attributed to C₆H₅‐C(?S)OSO₂^?. Copyright © 2009 John Wiley & Sons, Ltd.