Peptide cation-radicals. A computational study of the competition between peptide N-Calpha bond cleavage and loss of the side chain in the [GlyPhe-NH2 + 2H]+. cation-radical

Cation‐radicals and dications corresponding to hydrogen atom adducts to N‐terminus‐protonated N_α‐glycylphenylalanine amide (Gly‐Phe‐NH₂) are studied by combined density functional theory and Møller‐Plesset perturbational computations (B3‐MP2) as models for electron‐capture dissociation of peptide bonds and elimination of side‐chain groups in gas‐phase peptide ions. Several structures are identified as local energy minima including isomeric aminoketyl cation‐radicals, and hydrogen‐bonded ion‐radicals, and ylid‐cation‐radical complexes. The hydrogen‐bonded complexes are substantially more stable than the classical aminoketyl structures. Dissociations of the peptide N? C_α bonds in aminoketyl cation‐radicals are 18–47 kJ mol^?1 exothermic and require low activation energies to produce ion‐radical complexes as stable intermediates. Loss of the side‐chain benzyl group is calculated to be 44 kJ mol^?1 endothermic and requires 68 kJ mol^?1 activation energy. Rice‐Ramsperger‐Kassel‐Marcus (RRKM) and transition‐state theory (TST) calculations of unimolecular rate constants predict fast preferential N? C_α bond cleavage resulting in isomerization to ion‐molecule complexes, while dissociation of the C_α? CH₂C₆H₅ bond is much slower. Because of the very low activation energies, the peptide bond dissociations are predicted to be fast in peptide cation‐radicals that have thermal (298 K) energies and thus behave ergodically. Copyright © 2003 John Wiley & Sons, Ltd.     

N[bond]C(alpha) bond dissociation energies and kinetics in amide and peptide radicals. Is the dissociation a non-ergodic process?

Dissociations of aminoketyl radicals and cation radicals derived from beta-alanine N-methylamide, N-acetyl-1,2-diaminoethane, N(alpha)-acetyl lysine amide, and N(alpha)-glycyl glycine amide are investigated by combined density functional theory and M?ller-Plesset perturbational calculations with the goal of elucidating the mechanism of electron capture dissociation (ECD) of larger peptide and protein ions. The activation energies for dissociations of N[bond]C bonds in aminoketyl radicals decrease in the series N[bond]CH(3) > N-CH(2)CH(2)NH(2) > N[bond]CH(2)CONH(2) approximately N[bond]CH(CONH(2))(CH(2))(4)NH(2). Transition state theory rate constants for dissociations of N[bond]C(alpha) bonds in aminoketyl radicals and cation-radicals indicate an extremely facile reaction that occurs with unimolecular rate constants >10(5) s(-1) in species thermalized at 298 K in the gas phase. In neutral aminoketyl radicals the N[bond]C(alpha) bond cleavage results in fast dissociation. In contrast, N[bond]C(alpha) bond cleavage in aminoketyl cation-radicals results in isomerization to ion-molecule complexes that are held together by strong hydrogen bonds. The facile N[bond]C(alpha) bond dissociation in thermalized ions indicates that it is unnecessary to invoke the hypothesis of non-ergodic behavior for ECD intermediates.     

Stereospecific control of peptide gas‐phase ion chemistry with cis and trans cyclo ornithine residues

We report non‐chiral amino acid residues cis‐ and trans‐1,4‐diaminocyclohexane‐1‐carboxylic acid (cyclo‐ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen‐rich cation radicals produced by electron‐transfer dissociation. Upon collision‐induced dissociation (CID) in the slow heating regime, peptide cations containing trans‐cO residues undergo facile backbone cleavages of amide bonds C‐terminal to trans‐cO. By contrast, peptides with cis‐cO residues undergo dissociations at several amide bonds along the peptide ion backbone. Diastereoisomeric cO‐containing peptides thus provide remarkably distinct tandem mass spectra. The stereospecific effect in CID of the trans‐cO residue is explained by syn‐facially directed proton transfer from the 4‐ammonium group at cO to the C‐terminal amide followed by neighboring group participation in the cleavage of the CO―NH bond, analogous to the aspartic acid and ornithine effects. Backbone dissociations of diastereoisomeric cO‐containing peptide ions generate distinct [b_n]⁺‐type fragment ions that were characterized by CID‐MS³ spectra. Stereospecific control is also reported for electron‐transfer dissociation of cis‐ and trans‐cO containing doubly charged peptide ions. The stereospecific effect upon electron transfer is related to the different conformations of doubly charged peptide ions that affect the electron attachment sites and ensuing N―C_α bond dissociations.     

Two isomers of 2,4‐di­benzyl‐8‐azabicyclo­[3.2.1]­octan‐3‐ol

The crystal structures of the title compounds, 2α,4α‐di­benzyl‐3α‐tropanol (2α,4α‐di­benzyl‐8‐methyl‐8‐aza­bi­cyclo­[3.2.1]­octan‐3α‐ol), C₂₂H₂₇NO, (I), and 2α,4α‐di­benzyl‐3β‐tropanol (2α,4α‐di­benzyl‐8‐methyl‐8‐aza­bi­cyclo­[3.2.1]­octan‐3β‐ol), C₂₂H₂₇NO, (II), show that both compounds have a piperidine ring in a chair conformation and a pyrrolidine ring in an envelope conformation. Isomer (I) is asymmetric, the benzyl groups having different orientations, whereas isomer (II) is mirror symmetric, and the N and O atoms, the C atom attached to the hydroxy group, and the methyl C atom attached to the N atom lie on the mirror plane. In the crystal structures of both (I) and (II), the mol­ecules are linked together by intermolecular O—H⋯N hydrogen bonds to form chains that run parallel to the a direction in (I) and parallel to b in (II).     

Disulfide bond cleavage in TEMPO-free radical initiated peptide sequencing mass spectrometry

The gas‐phase free radical initiated peptide sequencing (FRIPS) fragmentation behavior of o‐TEMPO‐Bz‐conjugated peptides with an intra‐ and intermolecular disulfide bond was investigated using MSⁿ tandem mass spectrometry experiments. Investigated peptides included four peptides with an intramolecular cyclic disulfide bond, Bactenecin (RLC RIVVIRVC R), TGF‐α (C HSGYVGVRC ), MCH (DFDMLRC MLGRVFRPC WQY) and Adrenomedullin (16–31) (C RFGTC TVQKLAHQIY), and two peptides with an intermolecular disulfide bond. Collisional activation of the benzyl radical conjugated peptide cation, which was generated through the release of a TEMPO radical from o‐TEMPO‐Bz‐conjugated peptides upon initial collisional activation, produced a large number of peptide backbone fragments in which the S? S or C? S bond was readily cleaved. The observed peptide backbone fragments included a‐, c‐, x‐ or z‐types, which indicates that the radical‐driven peptide fragmentation mechanism plays an important role in TEMPO‐FRIPS mass spectrometry. FRIPS application of the linearly linked disulfide peptides further showed that the S? S or C? S bond was selectively and preferentially cleaved, followed by peptide backbone dissociations. In the FRIPS mass spectra, the loss of ?SH or ?SSH was also abundantly found. On the basis of these findings, FRIPS fragmentation pathways for peptides with a disulfide bond are proposed. For the cleavage of the S? S bond, the abstraction of a hydrogen atom at C_β by the benzyl radical is proposed to be the initial radical abstraction/transfer reaction. On the other hand, H‐abstraction at C_α is suggested to lead to C? S bond cleavage, which yields [ion ± S] fragments or the loss of ?SH or ?SSH. Copyright © 2011 John Wiley & Sons, Ltd.     

Bond dissociations in hypervalent ammonium radicals prepared by collisional neutralization of protonated six-membered nitrogen heterocycles

Hypervalent organic ammonium radicals were generated by collisional neutralization with dimethyl disulfide of protonated 1,4-diazabicyclo[2.2.2]octane (1H⁺), N,N′-dimethylpiperazine (2H⁺) and N-methylpiperazine (3H⁺). The radicals dissociated completely on the 5.1 μs time-scale. Radical 1H^• underwent competitive N−H and N−C bond dissociations producing 1,4-diazabicyclo[2.2.2]octane and small ring fragments. Dissociations of radical 2H^• proceeded by N−H bond dissociation and ring cleavage, whereas N−CH₃ bond cleavage was less frequent. Radical 3H^• underwent N−H, N−CH₃ and N−C_ring bond cleavages followed by post-reionization dissociations of the formed cations. The pattern of bond dissociations in the hypervalent ammonium radicals derived from six-membered nitrogen heterocycles is similar to those of aliphatic ammonium radicals. © 1997 John Wiley & Sons, Ltd.     

Electron transfer to protonated beta-alanine N-methylamide in the gas phase: an experimental and computational study of dissociation energetics and mechanisms

Ammonium radicals derived from protonated beta-alanine N-methyl amide (BANMA) were generated by femtosecond collisional electron transfer to gas-phase cations prepared by chemical ionization and electrospray. Regardless of the mode of precursor ion preparation, the radicals underwent complete dissociation on the time scale of 5.15 micros. Deuterium isotope labeling and product analysis pointed out several competitive and convergent dissociation pathways that were not completely resolved by experiment. Ab initio calculations, which were extrapolated up to the CCSD(T)/6-311++G(3df,2p) level of theory, provided the proton affinity and gas-phase basicity of BANMA as PA = 971 kJ mol-1 and GB = 932 kJ mol-1 to form the most stable ion structure 1c+ in which the protonated ammonium group was internally solvated by hydrogen bonding to the amide carbonyl. Ion 1c+ was calculated to have an adiabatic recombination energy of 3.33 eV to form ammonium radical 1c*. The potential energy surface for competitive and consecutive isomerizations and dissociations of 1c* was investigated at correlated levels of theory and used for Rice-Ramsperger-Kassel-Marcus (RRKM) calculations. RRKM unimolecular rate constants suggested that dissociations starting from the ground electronic state of radical 1c* were dominated by loss of an ammonium hydrogen atom. In contrast, dissociations starting from the B excited state were predicted to proceed by reversible isomerization to an aminoketyl radical (1f*). The latter can in part dissociate by N-Calpha bond cleavage leading to the loss of the amide methyl group. This indicates that apparently competitive dissociations observed for larger amide and peptide radicals, such as backbone cleavages and losses of side-chain groups, may originate from different electronic states and proceed on different potential energy surfaces.     

Hypervalent radical formation probed by electron transfer dissociation of zwitterionic tryptophan and tryptophan‐containing dipeptides complexed with Ca2+ and 18‐crown‐6 in the gas phase

The relationship between peptide structure and electron transfer dissociation (ETD) is important for structural analysis by mass spectrometry. In the present study, the formation, structure and reactivity of the reaction intermediate in the ETD process were examined using a quadrupole ion trap mass spectrometer equipped with an electrospray ionization source. ETD product ions of zwitterionic tryptophan (Trp) and Trp‐containing dipeptides (Trp‐Gly and Gly‐Trp) were detected without reionization using non‐covalent analyte complexes with Ca²⁺ and 18‐crown‐6 (18C6). In the collision‐induced dissociation, NH₃ loss was the main dissociation pathway, and loss related to the dissociation of the carboxyl group was not observed. This indicated that Trp and its dipeptides on Ca²⁺(18C6) adopted a zwitterionic structure with an NH₃⁺ group and bonded to Ca²⁺(18C6) through the COO^? group. Hydrogen atom loss observed in the ETD spectra indicated that intermolecular electron transfer from a molecular anion to the NH₃⁺ group formed a hypervalent ammonium radical, R‐NH₃, as a reaction intermediate, which was unstable and dissociated rapidly through N–H bond cleavage. In addition, N–C_α bond cleavage forming the z₁ ion was observed in the ETD spectra of Trp‐GlyCa²⁺(18C6) and Gly‐TrpCa²⁺(18C6). This dissociation was induced by transfer of a hydrogen atom in the cluster formed via an N–H bond cleavage of the hypervalent ammonium radical and was in competition with the hydrogen atom loss. The results showed that a hypervalent radical intermediate, forming a delocalized hydrogen atom, contributes to the backbone cleavages of peptides in ETD. Copyright © 2015 John Wiley & Sons, Ltd.     

Vacancy‐Rich Ni(OH)2 Drives the Electrooxidation of Amino C−N Bonds to Nitrile C≡N Bonds

Electrochemical synthesis based on electrons as reagents provides a broad prospect for commodity chemical manufacturing. A direct one‐step route for the electrooxidation of amino C?N bonds to nitrile C≡N bonds offers an alternative pathway for nitrile production. However, this route has not been fully explored with respect to either the chemical bond reforming process or the performance optimization. Proposed here is a model of vacancy‐rich Ni(OH)₂ atomic layers for studying the performance relationship with respect to structure. Theoretical calculations show the vacancy‐induced local electropositive sites chemisorb the N atom with a lone pair of electrons and then attack the corresponding N(sp³)?H, thus accelerating amino C?N bond activation for dehydrogenation directly into the C≡N bond. Vacancy‐rich nanosheets exhibit up to 96.5 % propionitrile selectivity at a moderate potential of 1.38 V. These findings can lead to a new pathway for facilitating catalytic reactions in the chemicals industry.     

Toward a general mechanism of electron capture dissociation

The effects of positive charge on the properties of ammonium and amide radicals were investigated by ab initio and density functional theory calculations with the goal of elucidating the energetics of electron capture dissociation (ECD) of multiply charged peptide ions. The electronic properties of the amide group in N-methylacetamide (NMA) are greatly affected by the presence of a remote charge in the form of a point charge, methylammonium, or guanidinium cations. The common effect of the remote charge is an increase of the electron affinity of the amide group, resulting in exothermic electron capture. The N-Calpha bond dissociation and transition state energies in charge-stabilized NMA anions are 20-50 kJ mol(-1) greater than in the hydrogen atom adduct. The zwitterions formed by electron capture have proton affinities that were calculated as 1030-1350 kJ mol(-1), and are sufficiently basic for the amide carbonyl to exothermically abstract a proton from the ammonium, guanidinium and imidazolium groups in protonated lysine, arginine, and histidine residues, respectively. A new mechanism is proposed for ECD of multiply charged peptide and protein cations in which the electron enters a charge-stabilized electronic state delocalized over the amide group, which is a superbase that abstracts a proton from a sterically proximate amino acid residue to form a labile aminoketyl radical that dissociates by N-Calpha bond cleavage. This mechanism explains the low selectivity of N-Calpha bond dissociations induced by electron capture, and is applicable to dissociations of peptide ions in which the charge carriers are metal ions or quaternary ammonium groups. The new amide superbase and the previously proposed mechanisms of ECD can be uniformly viewed as being triggered by intramolecular proton transfer in charge-reduced amide cation-radicals. In contrast, remote charge affects N-H bond dissociation in weakly bound ground electronic states of hypervalent ammonium radicals, as represented by methylammonium, CH3NH3*, but has a negligible effect on the N-H bond dissociation in the strongly bound excited electronic states. This refutes previous speculations that loss of "hot hydrogen" can occur from an excited state of an ammonium radical.     

Synthese eines funktionalen Aluminiumalkinids,Me3C‐C≡C‐AlBr2, und dessen Reaktionen mit der sperrigen Lithiumverbindung LiCH(SiMe3)2

Synthesis of a Functional Aluminium Alkynide, Me₃C‐C≡C‐AlBr₂, and its Reactions with the Bulky Lithium Compound LiCH(SiMe₃)₂ Treatment of aluminium tribromide with the lithium alkynide (Li)C≡C‐CMe₃ afforded the aluminium alkynide Me₃C‐C≡C‐AlBr₂ ( 1 ) in an almost quantitative yield. 1 crystallizes with trimeric formula units possessing Al₃C₃ heterocycles and the anionic carbon atoms of the alkynido groups in the bridging positions. A dynamic equilibrium was determined in solution which probably comprises trimeric and dimeric formula units. Reaction of 1 with one equivalent of LiCH(SiMe₃)₂ yielded the compound [Me₃C‐C≡C‐Al(Br)‐CH(SiMe₃)₂]₂ ( 2 ), which is a dimer via Al‐C‐Al bridges. Two equivalents of the lithium compound gave a mixture of four main‐products, which could be identified as 2 , Li[Me₃C‐C≡C‐Al{CH(SiMe₃)₂}₃] ( 3 ), Me₃C‐C≡C‐Al[CH(SiMe₃)₂]₂ ( 4 ), and Al[CH(SiMe₃)₂]₃. The lithium atom of 3 is coordinated by the C≡C triple bond and an inner carbon atom of one bis(trimethylsilyl)methyl group. Further interactions were observed to C‐H bonds of methyl groups.     

4‐Fluoro‐2‐(phospho­no­methyl)­benzene­sulfonic acid monohydrate

The title compound, C₇H₈FO₆PS·H₂O, contains both phospho­nic and sulfonic acid functionalities. An extensive network of O—H?O hydrogen bonds is present in the crystal structure. The three acidic protons are associated with the phospho­nate group. Two protons experience typical hydrogen‐bond contacts with the sulfonate‐O atoms, while the third has a longer covalent bond of 1.05 (3) Å to the phospho­nate‐O atom and a short hydrogen‐bond contact of 1.38 (3) Å to the water O atom (all O—H?O angles are in the range 162–175°). The sulfonate group is positioned so that one S—O bond is nearly coplanar with the phenyl ring [torsion angle O—S—C—C ?8.6 (2)°]. The phospho­nate group is oriented approximately perpendicular to the ring [torsion angle P—C—C—C 99.2 (2)°] with one P—O bond anti to the benzyl C—C bond. The mol­ecules pack in layers in the b–c plane with the water mol­ecules in between adjacent pairs of inverted layers.     

The first N‐terminal unprotected (Gly‐Aib)n peptide: H‐Gly‐Aib‐Gly‐Aib‐OtBu

Glycine (Gly) is incorporated in roughly half of all known peptaibiotic (nonribosomally biosynthesized antibiotic peptides of fungal origin) sequences and is the residue with the greatest conformational flexibility. The conformational space of Aib (α‐aminoisobutyric acid) is severely restricted by the second methyl group attached to the C_α atom. Most of the crystal structures containing Aib are N‐terminal protected. Deprotection of the N‐ or C‐terminus of peptides may alter the hydrogen‐bonding scheme and/or the structure and may facilitate crystallization. The structure reported here for glycyl‐α‐aminoisobutyrylglycyl‐α‐aminoisobutyric acid tert‐butyl ester, C₁₆H₃₀N₄O₅, describes the first N‐terminal‐unprotected (Gly‐Aib)_n peptide. The achiral peptide could form an intramolecular hydrogen bond between the C=O group of Gly1 and the N—H group of Aib4. This hydrogen bond is found in all tetrapeptides and N‐terminal‐protected tripeptides containing Aib, apart from one exception. In the present work, this hydrogen bond is not observed (N...O = 5.88 Å). Instead, every molecule is hydrogen bonded to six other symmetry‐related molecules with a total of eight hydrogen bonds per molecule. The backbone conformation starts in the right‐handed helical region (and the left‐handed helical region for the inverted molecule) and reverses the screw sense in the last two residues.     

The arginine anomaly: arginine radicals are poor hydrogen atom donors in electron transfer induced dissociations

Arginine amide radicals are generated by femtosecond electron transfer to protonated arginine amide cations in the gas phase. A fraction of the arginine radicals formed (2-amino-5-dihydroguanid-1'-yl-pentanamide, 1H) is stable on the 6.7 micros time scale and is detected after collisional reionization. The main dissociation of 1H is loss of a guanidine molecule from the side chain followed by consecutive dissociations of the 2-aminopentanamid-5-yl radical intermediate. Intramolecular hydrogen atom transfer from the guanidinium group onto the amide group is not observed. These results are explained by ab initio and density functional theory calculations of dissociation and transition state energies. Loss of guanidine from 1H is calculated to require a transition state energy of 68 kJ mol(-)(1), which is substantially lower than that for hydrogen atom migration from the guanidine group. The loss of guanidine competes with the reverse migration of the arginine alpha-hydrogen atom onto the guanidyl radical. RRKM calculations of dissociation kinetics predict the loss of guanidine to account for >95% of 1H dissociations. The anomalous behavior of protonated arginine amide upon electron transfer provides an insight into electron capture and transfer dissociations of peptide cations containing arginine residues as charge carriers. The absence of efficient hydrogen atom transfer from charge-reduced arginine onto sterically proximate amide group blocks one of the current mechanisms for electron capture dissociation. Conversely, charge-reduced guanidine groups in arginine residues may function as radical traps and induce side-chain dissociations. In light of the current findings, backbone dissociations in arginine-containing peptides are predicted to involve excited electronic states and proceed by the amide superbase mechanism that involves electron capture in an amide pi* orbital, which is stabilized by through-space coulomb interaction with the remote charge carriers.     

Two new thiophosphoramide structures: N,N′,N′′‐tricyclohexylphosphorothioic triamide and O,O′‐diethyl (2‐phenylhydrazin‐1‐yl)thiophosphonate

The compound N,N′,N′′‐tricyclohexylphosphorothioic triamide, C₁₈H₃₆N₃PS or P(S)[NHC₆H₁₁]₃, (I), crystallizes in the space group Pnma with the molecule lying across a mirror plane; one N atom lies on the mirror plane, whereas the bond‐angle sum at the other N atom has a deviation of some 8° from the ideal value of 360° for a planar configuration. The orientation of the atoms attached to this nonplanar N atom corresponds to an anti orientation of the corresponding lone electron pair (LEP) with respect to the P=S group. The P=S bond length of 1.9785 (6) Å is within the expected range for compounds with a P(S)[N]₃ skeleton; however, it is in the region of the longest bond lengths found for analogous structures. This may be due to the involvement of the P=S group in N—H...S=P hydrogen bonds. In O,O′‐diethyl (2‐phenylhydrazin‐1‐yl)thiophosphonate, C₁₀H₁₇N₂O₂PS or P(S)[OC₂H₅]₂[NHNHC₆H₅], (II), the bond‐angle sum at the N atom attached to the phenyl ring is 345.1°, whereas, for the N atom bonded to the P atom, a practically planar environment is observed, with a bond‐angle sum of 359.1°. A Cambridge Structural Database [CSD; Allen (2002). Acta Cryst. B 58 , 380–388] analysis shows a shift of the maximum population of P=S bond lengths in compounds with a P(S)[O]₂[N] skeleton to the shorter bond lengths relative to compounds with a P(S)[N]₃ skeleton. The influence of this difference on the collective tendencies of N...S distances in N—H...S hydrogen bonds for structures with P(S)[N]₃ and P(S)[O]₂[N] segments were studied through a CSD analysis.     

Imines in the Titanium Coordination Sphere – Transformation of Imidoyl Chlorides to Nitrilium Ions

In the reaction of TiCl₄ in benzene as solvent with the imidoyl chloride p‐Tolyl(Cl)C=NPh ( 1 ) the abstraction of the chloride substituent is observed, leading to the nitrilium salt [p‐Tolyl–C≡N–Ph]⁺[Ti₂Cl₉]^– ( 2 ) in quantitative yield. The highly electrophilic salt 2 is characterized by IR‐ and NMR spectroscopy. The observed band for the C≡N stretching mode of 2 clearly indicates the formation of a nitrilium ion. Especially a characteristic line broadening of the ¹³C{¹H}‐NMR signals related to carbon atoms next to the nitrogen is observed. By ¹⁵N,¹H‐HMBC NMR experiments it is shown that the nitrogen signal of 2 is significantly shifted to high‐field in relation to nitriles and imines. The molecular structure of 2 was confirmed by single‐crystal X‐ray diffraction. The C≡N bond length and the linearity of the C–C≡N–C unit in 2 confirm the triple bond character of this bond.     

N‐Benzylnicotinamide and N‐benzyl‐1,4‐dihydronicotinamide: useful models for NAD+ and NADH

3‐Aminocarbonyl‐1‐benzylpyridinium bromide (N‐benzylnicotinamide, BNA), C₁₃H₁₃N₂O⁺·Br⁻, (I), and 1‐benzyl‐1,4‐dihydropyridine‐3‐carboxamide (N‐benzyl‐1,4‐dihydronicotinamide, rBNA), C₁₃H₁₄N₂O, (II), are valuable model compounds used to study the enzymatic cofactors NAD(P)⁺ and NAD(P)H. BNA was crystallized successfully and its structure determined for the first time, while a low‐temperature high‐resolution structure of rBNA was obtained. Together, these structures provide the most detailed view of the reactive portions of NAD(P)⁺ and NAD(P)H. The amide group in BNA is rotated 8.4 (4)° out of the plane of the pyridine ring, while the two rings display a dihedral angle of 70.48 (17)°. In the rBNA structure, the dihydropyridine ring is essentially planar, indicating significant delocalization of the formal double bonds, and the amide group is coplanar with the ring [dihedral angle = 4.35 (9)°]. This rBNA conformation may lower the transition‐state energy of an ene reaction between a substrate double bond and the dihydropyridine ring. The transition state would involve one atom of the double bond binding to the carbon ortho to both the ring N atom and the amide substituent of the dihydropyridine ring, while the other end of the double bond accepts an H atom from the methylene group para to the N atom.     

Reactivity Study of Pyridyl‐Substituted 1‐Metalla‐2,5‐diaza‐cyclopenta‐2,4‐dienes of Group 4 Metallocenes

In this work the reactivity of 1‐metalla‐2,5‐diaza‐cyclopenta‐2,4‐dienes of group 4 metallocenes, especially of the pyridyl‐substituted examples, towards small molecules is investigated. The addition of H₂, CO₂, Ph?C≡N, 2‐py?C≡N, 1,3‐dicyanobenzene or 2,6‐dicyanopyridine results in exchange reactions, which are accompanied by the elimination of a nitrile. For CO₂, a coordination to the five‐membered cycle occurs in case of Cp*₂Zr(N=C(2‐py)?C(2‐py)=N). A 1,4‐diaza‐buta‐1,3‐diene complex is formed by H‐transfer in the conversion of the analogous titanocene compound with CH₃?C≡N, PhCH₂?C≡N or acetone. For CH₃?C≡N a coupling product of three acetonitrile molecules is established additionally. In order to split off the metallocene from the coupled nitriles, we examined reactions with HCl, PhPCl₂, PhPSCl₂ and SOCl₂. In the last case, the respective thiadiazole oxides and the metallocene dichlorides were obtained. A subsequent reaction produced thiadiazoles.     

Dissociation behaviors of carboxyl and amine groups on carboxymethyl‐chitosan in aqueous system

Several carboxymethyl‐chitosan (CMCS) samples with different deacetylation degree and/or substituted degree were prepared from the carboxymethylation reaction of chitosan under soft conditions. The products were dissolved in standard HCl aqueous solution to carry out potentiometric titration by using NaOH as titrating solution at different ionic strengths. Then the dissociation behaviors of protonated carboxyl and amine groups were investigated under their degree of dissociation (α) and protonation constant (pK_α) had been calculated. Moreover, influences of the intrinsic and extrinsic parameters on the dissociation behavior of CMCS were also considered in this article. As a result, dissociations of carboxyl and amine on CMCS exhibited unusual behaviors in comparison with carboxyl of carboxymethyl‐cellulose and amine groups of chitosan, respectively. The pK_α values of carboxyl declined slightly at early dissociation stage but subsequently maintained constant. In contrast, the pK_α of ammonium increased with its dissociation degree despite that there was an inflexed change on its dissociation curve. The potentiometric behavior of carboxyl was hardly affected by variation of deacetylation degree or substituted degree. However, these intrinsic parameters played more important role on dissociations of ammonium on CMCS. The ionic strength of media could bring screening effect on dissociaciation of both sorts of ionizable groups of CMCS. By increasing the ionic strength of media, screening effect on dissociations increased significantly. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1419–1429, 2008     

Charge‐Assisted Halogen Bonding: Donor–Acceptor Complexes with Variable Ionicity

Charge‐assisted halogen bonding is unambiguously revealed from structural and electronic investigations of a series of isostructural charge‐transfer complexes derived from iodinated tetrathiafulvalene and tetracyanoquinodimethane derivatives, (EDT‐TTFI₂)₂(TCNQF_n), n=0–2, which exhibit variable degrees of ionicity. The iodinated tetrathiafulvalene derivative, EDT‐TTFI₂, associates with tetracyanoquinodimethane (TCNQ) and its derivatives of increasing reduction potential (TCNQF, TCNQF₂) through highly directional C? I???N≡C halogen‐bond interactions. With the less oxidizing TCNQ acceptor, a neutral and insulating charge‐transfer complex is isolated whereas with the more oxidizing TCNQF₂ acceptor, an ionic, highly conducting charge‐transfer salt is found, both of 2:1 stoichiometry and isostructural with the intermediate TCNQF complex, in which a neutral–ionic conversion takes place upon cooling. A correlation between the degree of charge transfer and the C? I???N≡C halogen‐bond strength is established from the comparison of the structures of the three isostructural complexes at temperatures from 300 to 20 K, thus demonstrating the importance of electrostatics in the halogen‐bonding interaction. The neutral–ionic conversion in (EDT‐TTFI₂)₂(TCNQF) is further investigated through the temperature dependence of its magnetic susceptibility and the stretching modes of the C≡N groups.