The fragmentations of [M-H]- anions derived from underivatised peptides. The side-chain loss of H2S from Cys. A joint experimental and theoretical study

Loss of H₂S is the characteristic Cys side‐chain fragmentation of the [M? H]^? anions of Cys‐containing peptides. A combination of experiment and theory suggests that this reaction is initiated from the Cys enolate anion as follows: RNH‐^?C(CH₂SH)CONHR′ Ø [RNHC(?CH₂)CONHR′ (HS^?)] Ø [RNHC(?CH₂)CO‐HNR′‐H]^?+H₂S. This process is facile. Calculations at the HF/6‐31G(d)//AM1 level of theory indicate that the initial anion needs only ≥20.1 kcal mol^?1 of excess energy to effect loss of H₂S. Loss of CH₂S is a minor process, RNHCH(CH₂SH)CON^?‐R′ Ø RNHCH(CH₂S^?)CONHR′ Ø RNH ^?CHCONHR+CH₂S, requiring an excess energy of ≥50.2 kcal mol^?1. When Cys occupies the C‐terminal end of a peptide, the major fragmentation from the [M–H]^? species involves loss of (H₂S+CO₂). A deuterium‐labelling study suggests that this could either be a charge‐remote reaction (a process which occurs remote from and uninfluenced by the charged centre in the molecule), or an anionic reaction initiated from the C‐terminal CO₂^? group. These processes have barriers requiring the starting material to have an excess energy of ≥79.6 (charge‐remote) or ≥67.1 (anion‐directed) kcal mol^?1, respectively, at the HF/6‐31G(d)//AM1 level of theory. The corresponding losses of CH₂O and H₂O from the [M? H]^? anions of Ser‐containing peptides require ≥35.6 and ≥44.4 kcal mol^?1 of excess energy (calculated at the AM1 level of theory), explaining why loss of CH₂O is the characteristic side‐chain loss of Ser in the negative ion mode. Copyright © 2003 John Wiley & Sons, Ltd.     

Condensation of [Si3O9]6- anions in the solid state to the dimeric cyclotrisilicate anion [Si6O17]10-

The structure of the silicate Rb10[Si6O17] containing a novel dimeric cyclotrisilicate anion is reported. The compound is formed by the reaction of a mixture of SiO2 and Rb at temperatures above 700 degrees C. Systematic investigations by means of differential thermal analysis and temperature-dependent powder X-ray diffraction experiments revealed that the new compound evolved from Rb6[Si3O9], which occurred as an intermediate product. Thus, the dimeric anion [Si6O17]10- is formed by condensation of the monomeric cyclotrisilicate [Si3O9]6-. For both silicates, [Si6O17]10- and [Si3O9]6-, the characteristic ring vibration modes were observed in the IR spectrum. The structure of Rb10[Si6O17] was solved and refined from single-crystal X-ray diffraction data in the orthorhombic space group Pbca (No. 61). Synthesis and structure determination of Rb10[Si6O17] bridge the gap to show that the recently reported structures of Rb14[Si4][Si6O17] and Rb14[Ge4][Si6O17] are indeed fascinating intergrowth structures of the stable oxide Rb10[Si6O17] and the Zintl phases RbSi (Rb4Si4) and RbGe (Rb4Ge4), respectively.     

Evaluation of the binding ability of tetraaza[2]arene[2]triazine receptors anchoring l-alanine units for aromatic carboxylate anions

The binding affinities of three new tetraaza[2]arene[2]triazine based macrocycles anchoring one (AC1A) and two (AC2A and Me₄AC2A) l-alanine amino acid units for five aromatic carboxylate anions (bz^?, ph^2?, iph^2?, tph^2? and btc^3?) were investigated in DMSO-d₆. ¹H NMR titrations revealed that the AC1A and AC2A receptors exhibit comparable anion affinities, suggesting that the two l-alanine binding units in AC2A are not simultaneously involved in the anion recognition as indicated by molecular dynamics simulations carried out for selected AC1A and AC2A associations using the AMBER force field (GAFF). New force field parameters were developed in order to mimic the structural singularity derived from the N–H macrocyclic bridges.     

Backbone cleavages of [M - H](-) anions derived from caerin 1 peptides and some synthetic modifications. Molecular recognition initiating internal cyclisation of Glu23

The collision induced spectra of [M - H](-) anions from of caerin 1 peptides and some synthetic modifications show the usual alpha, beta and beta' backbone cleavages together with Ser (epsilon,gamma) and Glu (gamma) cleavages which break the peptide backbone in the vicinity of those residues. All of these cleavages require the peptide backbone to be flexible. There is also a backbone cleavage of a type not observed before. This cleavage involves nucleophilic attack of the carboxylate anion of the Glu23 side chain at the backbone CH of Ile 21. We propose that this cleavage requires the caerin peptide to be in an alpha helical conformation (the 3D structure that this peptide adopts in solution) in order that the interacting groups are held in close proximity.     

Gas-phase chemistry of diphosphate anions as a tool to investigate the intrinsic requirements of phosphate ester enzymatic reactions: the [M1M2HP2O7]- ions

Experimental studies on gaseous inorganic phosphate ions are practically nonexistent, yet they can prove helpful for a better understanding of the mechanisms of phosphate ester enzymatic processes. The present contribution extends our previous investigations on the gas-phase ion chemistry of diphosphate species to the [M(1)M(2)HP(2)O(7)](-) ions where M(1) and M(2) are the same or different and correspond to the Li, Na, K, Cs, and Rb cations. The diphosphate ions are formed by electrospray ionization of 10(-4) M solutions of Na(5)P(3)O(10) in CH(3)CN/H(2)O (1/1) and MOH bases or M salts as a source of M(+) cations. The joint application of mass spectrometric techniques and quantum-mechanical calculations makes it possible to characterize the gaseous [M(1)M(2)HP(2)O(7)](-) ions as a mixed ionic population formed by two isomeric species: linear diphosphate anion coordinated to two M(+) cations (group I) and [PO(3)M(1)M(2)HPO(4)](-) clusters (group II). The relative gas-phase stabilities and activation barriers for the isomerization I-->II, which depend on the nature of the M(+) cations, highlight the electronic susceptibility of P-O-P bond breaking in the active site of enzymes. The previously unexplored gas-phase reactivity of [M(1)M(2)HP(2)O(7)](-) ions towards alcohols of different acidity was investigated by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). The reaction proceeds by addition of the alcohol molecule followed by elimination of a water molecule.     

Electron transfer and CO addition to polynitrido cobalt carbonyl clusters: parallel pathways for conversion of the [Co10N2(CO)19]4- anion to the novel [Co11N2(CO)21]3- anion

The redox aptitude of the dinitrido anion [Co10N2(CO)19]4- has been tested from both chemical and electrochemical points of view, together with its reactivity toward CO that induces disproportionation. In any case, through a remarkable overlapping of intermediate steps, the new anion [Co11N2(CO)21]3- (4) is eventually obtained. A detailed study of the pathways to 4 allowed the identification of three labile intermediates by their characteristic IR spectra as well as their electrochemical and paramagnetic properties. The unprecedented structure of trianion 4 has been studied in details in two different crystalline salts.     

Electrochemical transfer of [18F]fluoride from [18O]water into organic solvents ready for labeling reactions

For labeling reactions [¹⁸F]fluoride has to be separated from [¹⁸O]water and transferred into an organic solvent suitable for nucleophilic substitutions. An electrolytical method is described for depositing [¹⁸F]fluoride on a vitreous carbon electrode and releasing it directly into CH₃CN or DMSO. In the presence of Et₃N×3HF, [¹⁸F]fluoride is almost quantitatively released into acetonitrile. When using n.c.a conditions, i.e., Et₃N^.HCl, desorption of the ¹⁸F activity is almost 70% and 60% in acetonitrile and DMSO, respectively, already within 5 minutes.     

Kinetics of proton transfer from benzo[b]-2,3-dihydrofuran-2-one and benzo[b]-2,3-dihydrothiophene-2-one. Effect of anion aromaticity on intrinsic barriers

Rates of the reversible deprotonation of benzo[b]-2,3-dihydrofuran-2-one (6H-O) and benzo[b]-2,3-dihydrothiophene-2-one (6H-S) by OH-, primary aliphatic amines, secondary alicyclic amines, and carboxylate ions have been determined in water at 25 degrees C. As noted earlier by Kresge and Meng, 6H-S (pKa = 8.82) is considerably more acidic than 6H-O (pKa = 11.68), which mainly reflects the greater aromatic stabilization of the conjugate base of 6H-S (thiophene derivative) compared to that of 6H-O (furan derivative). The main focus of this paper is to assess how the difference in the aromaticity of the two enolate ions affects the intrinsic barrier to the proton transfer. These intrinsic barriers were determined from Br?nsted plots for the reactions with the amines and carboxylate ions or calculated on the basis of the Marcus equation for the reactions with OH-. They are consistently somewhat higher for the reactions of 6H-S than for the reactions of 6H-O, implying that the aromaticity in the anion enhances the intrinsic barrier. This contrasts with a previous report on the deprotonation of some cyclic rhenium Fischer-type carbene complexes where the reaction that leads to the most aromatic conjugate base (thiophene derivative) has a lower intrinsic barrier than the reaction that leads to the less aromatic furan analogue. We are offering a detailed analysis of other potential factors that may affect the intrinsic barriers and which could explain these contradictory results.     

[7+2]- and [11+2]-cycloaddition reactions of diazo-azoles with isocyanates to azolo[5,1-d] [1,2,3,5] tetrazine-4-ones

Diazo-azoles react as 1,7- or 1,11-dipoles with isocyanates to form the hitherto unknown pyrazolo[5,1-d] [1,2,3,5]tetrazine-4-ones, [1,2,3,5]tetrazino[5,4-b]indazole-4-ones and [1,2,3]triazolo[5,1-d][1,2,3,5]tetrazine-4-ones in a [7+2]- or [11+2]-cycloaddition reaction.     

Crown compounds for anions: sandwich and half-sandwich complexes of cyclic trimetric perfluoro-o-phenylenemercury with polyhedral closo-[B10H10]2- and closo-[B12H12]2- anions

It has been shown by IR and NMR spectroscopy that cyclic trimeric perfluoro-o-phenylenemercury (o-C6F4-Hg)3 (1) is capable of binding closo-[B10H10]2- and closo-[B12H12]2- anions to form complexes [[(o-C6F4Hg)3](B10-H10)]2- (2), [[(o-C6F4Hg)3]2(B10H10)]2-(3), [[(o-C6F4Hg)3](B12H12)]2- (4), and [[(o-C6F4Hg)3]2(B12H12)]2- (5). According to IR data, the bonding of the [B10H10]2- and [B12H12]2- ions to the macrocycle in these complexes is accomplished through the formation of B-H-Hg bridges. Complexes 2, 3, and 5 have been isolated in analytically pure form and have been characterized by spectroscopic means. X-ray diffraction studies of 3 and 5 have revealed that these compounds have unusual sandwich structures, in which the polyhedral di-anion is located between the planes of two molecules of 1 and is bonded to each of them through two types of B-H-Hg bridges. One type is the simultaneous coordination of a B-H group to all three Hg atoms of the macrocycle. The other type is the coordination of a B-H group to a single Hg atom of the cycle. According to X-ray diffraction data, complex 2 has an analogous but half-sandwich structure. The obtained complexes 2-5 are quite stable; their stability constants in THF/acetone (1:1) at 20 degrees C have been determined as 1.0 x 10(2)Lmol(-1), 2.6 x 10(3)L(2)mol(2), 0.7 x 10(2)Lmol(-1), and 0.98 x 10(3)L(2)mol(-2), respectively.     

Stereoselective cascade reactions for construction of polyfunctionalised octahydroquinolines via [2C+2C+1C,1N] cyclisation

A conceptually unifying approach for a highly enantio- and diastereoselective synthesis of polyfunctionalised octrahydroquinolines incorporating three contiguous chiral centres is reported. The synthesis involves diphenylprolinol silyl ether-catalysed Michael addition of 1,3-cyclohexanedione to nitroalkenes followed by potassium carbonate-promoted aza-Henry reaction with N-tosyl aldimines, intramolecular hemiaminalisation and dehydration reaction cascade in a one-pot operation.     

Ligand movement modulates the rate of proton transfer in reactions of [Fe4S4Cl4]2-

Substitution of the first chloro-ligand in [Fe4S4Cl4]2- by 4-RC6H4S- (R = CF3, Cl, H, Me or MeO), in the presence of [H2N(CH2)3CH2]+, involves initial binding of thiolate, followed by protonation and finally chloride dissociation; the rate of protonation is facilitated by electron-withdrawing R-substituents indicating that Fe-thiolate bond length changes modulate proton transfer.     

Thiophilic addition of alkyllithium to dithiocarboxylic acid anions:synthesis of 2-[bis(alkylthio)methylene]-1,3-dithioles

2-lithio-4,5-disubstituted-1,3-dithioles react with CS₂ in thepresence of an excess organolithium reagents yielding a product of thiophilic addition; subsequent alkylation furnished a new series of2-[bis(alkylthio)methylene]-1,3-dithioles.     

Proton transfer reactions from N-H acid [5,10,15,20-tetrakis(pentafluorophenyl)-21-H, 23-H-porphyrin] to strong bases in acetonitrile

Deprotonation of 5,10,15,20-tetrakis(pentafluorophenyl)-21-H, 23-H-porphyrin (PhF₅PorH₂) by various bases has been studied by ¹H NMR and kinetic methods. The kinetic parameters in acetonitrile were defined for proton transfer reactions yielding [NH]⁺ protonated bases and [NHN]⁻ anions with intramolecular hydrogen-bonded chains.     

Backbone cleavages of [M - H](-) anions of peptides. Cyclisation of citropin 1 peptides involving reactions between the C-terminal [CONH](-) residue and backbone amide carbonyl groups. A new type of beta cleavage: a joint experimental and theoretical study

This paper reports the study of backbone cleavages in the collision-induced negative-ion mass spectra of the [M - H](-) anions of some synthetic modifications of the bioactive amphibian peptide citropin 1 (GLFDVIKKVASVIGGL-NH(2)). The peptides chosen for study contain no amino acid residues which could effect facile side-chain cleavage, i.e. Ser (-CH(2)O, side-chain cleavage) and Asp (-H(2)O) are replaced by Ala or Lys. We expected that such peptides should exhibit standard and pronounced peaks due to alpha cleavage ions (and to a lesser extent beta cleavage ions) in their collision-induced negative-ion spectra. This expectation was realised, but the spectra also contained peaks formed by a new series of cleavage anions. These are produced following cyclisation of the C-terminal CONH(-) moiety at carbonyl functions of amide groups along the peptide backbone; effectively transferring the NH of the C-terminal CONH(-) group to other amino acid residues. We have called the product anions of these processes beta' ions, in order to distinguish them from standard beta ions. Some beta' ions also fragment directly to some other beta' ions of smaller mass. The reaction coordinates of alpha,beta and beta' backbone processes have been calculated at the HF/6-31G*//AM1 level theory for simple model systems. The initial cyclisation step of the beta' sequence is barrierless and exothermic. Subsequent steps have a maximum barrier of +40 kcal mol(-1), with the overall reaction being endothermic by some 30 kcal mol(-1) at the level of theory used. These calculations take no account of the complexity of the conformationally flexible peptide system, and it is surprising that each of the two reacting centres can 'find' each other in such a large system.     

Switching off electron transfer reactions in confined media: reduction of [Co(dipic)2]- and [Co(edta)]- by hexacyanoferrate(II)

The kinetics of reduction of two cobalt(III) complexes with similar redox potentials by hexacyanoferrate(II) were investigated in water and in reverse micelle (RM) microemulsions. The RMs were composed of water, surfactant [(sodium(bis(2-ethylhexylsulfosuccinate)), NaAOT], and isooctane. Compared to the reaction in water, the reduction rates of (ethylenediaminetetraacetato)cobaltate(III) by hexacyanoferrate(II) were dramatically suppressed in RM microemulsions whereas a slight rate increase was observed for reduction of bis-(2,6-dipicolinato)cobaltate(III). For example, the ferrocyanide reduction of [Co(dipic)(2)](-) increased from 55 M(-1) s(-1)in aqueous media to 85 M(-1) s(-1) in a w(o) = 20 RM. The one-dimensional (1-D) and two-dimensional (2-D) (1)H NMR and FT-IR studies are consistent with the reduction rate constants of these two complexes being affected by their location within the RM. Since reduction of [Co(edta)](-) is switched off, in contrast to [Co(dipic)(2)](-), these observations are attributed to the penetration of the [Co(edta)](-) into the interfacial region of the RM whereas [Co(dipic)(2)](-) is in a region highly accessible to the water pool and thus hexacyanoferrate(II). These results demonstrated that compartmentalization completely turns off a redox reaction in a dynamic microemulsion system by either reactant separation or alteration of the redox potentials of the reactants.