Relative Stability of Peptide Sequence Ions Generated by Tandem Mass Spectrometry

We report the use of unimolecular dissociation by infrared radiation for gaseous multiphoton energy transfer to determine relative activation energy (E_a,laser) for dissociation of peptide sequence ions. The sequence ions of interest are mass-isolated; the entire ion cloud is then irradiated with a continuous wave CO₂ laser, and the first order rate constant, k_d, is determined for each of a series of laser powers. Provided these conditions are met, a plot of the natural logarithm of k_d versus the natural logarithm of laser power yields a straight line, whose slope provides a measure of E_a,laser. This method reproduces the E_a values from blackbody radiative dissociation (BIRD) for the comparatively large, singly and doubly protonated bradykinin ions (nominally y ₉ and y ₉ ²⁺ ). The comparatively small sequence ion systems produce E_a,laser values that are systematic underestimates of theoretical barriers calculated with density functional theory (DFT). However, the relative E_a,laser values are in qualitative agreement with the mobile proton model and available theory. Additionally, novel protonated cyclic-dipeptide (diketopiperazine) fragmentation reactions are analyzed with DFT. FT-ICR MS provides access to sequence ions generated by electron capture dissociation, infrared multiphoton dissociation, and collisional activation methods (i.e., b _n , y _m , c _n , z _m ^• ions).     

Pyridine adsorption on small Nin‐cluster (n = 2,3,4): A study of geometry and electronic structure

Adsorption of pyridine on Ni_n‐clusters (with n = 2,3,4) is studied by quantum chemical calculations at B3LYP/LANL2DZ and B3LYP/6‐311G^** levels. First, Ni_n‐clusters are investigated for accessible structure and electronic states. The lowest electronic state with four unpaired electrons is predicted for Ni₄‐cluster based on geometry and electronic structure, showing that the cluster stability nicely depends on number of unpaired electrons. Correction for basis set superposition error of metal‐metal bond is appreciable and has increasing effect on cluster binding energy. Next, adsorption of pyridine in planar and vertical adsorption modes is investigated on rhombus Ni₄‐cluster. The vertical mode is found (at B3LYP/6‐311G^** level) as the most favorable adsorption mode. Adsorption energy (ΔE_ads) depends on cluster size; adsorption on Ni₄‐cluster is most favorable with ΔE_ads = ?207.33 kJ/mol. The natural bond orbital analysis reveals the charge transfer in adsorbate/metal‐cluster. Results of investigations for the Ni₂‐ and Ni₃‐cluster are also presented. © 2012 Wiley Periodicals, Inc.     

The thermodynamic stability of P8, A CBS‐Q study

The thermodynamic stabilities of P₂, P₄, and three P₈ cage structure were investigated through high‐precision CBS‐Q calculations. The CBS‐Q values for the bond energy of P₂ (ΔE_o: +115.7 kcal mol⁻¹) and the formation of P₄ from P₂ (Δ E_o:‐56.6 kcal mol⁻¹) were in excellent agreement with the experimental values (E_o: +117 and ‐56.4 kcal mol⁻¹ respectively). Among the P₈ cages, the cubane structure was the least stable (Δ E_o +37 kcal vs. 2×P₄). The most stable P₈ isomer adopts a cuneane structure resembling S₄N₄, and is more stable than white phosphorus at T = 0 K (Δ E_o −3.3 kcal mol⁻¹), but still unstable under standard conditions for entropic reasons (Δ G^o of +8.1 kcal mol⁻¹ vs. 2×P₄). The CBS‐Q energies represent significant revisions (6–20 kcal mol⁻¹) of previous computational predictions obtained by high‐level single method calculations. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:453–457, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20119     

Conformational Relaxation of p‐Phenylenevinylene Trimers in Solution Studied by Picosecond Time‐Resolved Fluorescence

Two p‐phenylenevinylene (PV) trimers, containing 3′‐methylbutyloxyl (in MBOPV3) and 2′‐ethylhexyloxyl (in EHOPV3) side chains, are used as model compounds of PV‐based conjugated polymers (PPV) with the purpose of clarifying the origin of fast (picosecond time) components observed in the fluorescence decays of poly[2‐methoxy‐5‐(2′‐ethylhexyloxy)‐p‐phenylenevinylene] (MEH‐PPV). The fluorescence decays of MBOPV3 and EHOPV3 reveal the presence of similar fast components, which are assigned to excited‐state conformational relaxation of the initial population of non‐planar trimer conformers to lower‐energy, more planar conformers. The rate constant of conformational relaxation k_CR is dependent on solvent viscosity and temperature, according to the empirical relationship k_CR=aη_o^?α?exp(?αE_η/RT), where aη_o^?α is the frequency factor, η_o is the pre‐exponential coefficient of viscosity, E_η is the activation energy of viscous flow. The empirical parameter α, relating the solvent microscopic friction involved in the conformational change to the macroscopic solvent friction (α=1), depends on the side chain. The fast component in the fluorescence decays of MEH‐PPV polymers (PPVs), is assigned to resonance energy transfer from short to longer polymer segments. The present results call for revising this assignment/interpretation to account for the occurrence of conformational relaxation, concurrently with energy transfer, in PPVs.     

Alkylation Effects on the Energy Transfer of Highly Vibrationally Excited Naphthalene

The energy transfer of highly vibrationally excited isomers of dimethylnaphthalene and 2‐ethylnaphthalene in collisions with krypton were investigated using crossed molecular beam/time‐of‐flight mass spectrometer/time‐sliced velocity map ion imaging techniques at a collision energy of approximately 300 cm^?1. Angular‐resolved energy‐transfer distribution functions were obtained directly from the images of inelastic scattering. The results show that alkyl‐substituted naphthalenes transfer more vibrational energy to translational energy than unsubstituted naphthalene. Alkylation enhances the V→T energy transfer in the range ?ΔE_d=?100～?1500 cm^?1 by approximately a factor of 2. However, the maximum values of V→T energy transfer for alkyl‐substituted naphthalenes are about 1500～2000 cm^?1, which is similar to that of naphthalene. The lack of rotation‐like wide‐angle motion of the aromatic ring and no enhancement in very large V→T energy transfer, like supercollisions, indicates that very large V→T energy transfer requires special vibrational motions. This transfer cannot be achieved by the low‐frequency vibrational motions of alkyl groups.     

Serendipitous Discovery of Peptide Dialkyl Peroxides

In an attempt to synthesize a homologous series of peptide peresters, we investigated the reaction of the oxazol‐5(4H)‐ones of Pht‐(Aib)_n‐OH (n=2–8) and tert‐butyl hydroperoxide in the presence of 4‐(dimethylamino)pyridine. Unexpectedly, the major product isolated in each case proved to be the peptide dialkyl peroxide. This novel class of peptide derivatives was characterized by FT‐IR, ¹H‐NMR, MS, cyclic voltammetry, and X‐ray diffraction. On the basis of the experimental data, a plausible mechanism is proposed for this reaction.     

Effect of Preferential Solvation on the Thermodynamic Properties of Antidepressant Drug Trazodone in Aqueous Ethanol: Linear Free‐Energy Relationships

Dissociation constants (pK_a) of trazodone hydrochloride (TZD⋅HCl) in EtOH/H₂O media containing 0, 10, 20, 30, 40, 50, 60, 70, and 80% (v/v) EtOH at 288.15, 298.15, 308.15, and 318.15 K were determined by potentiometric techniques. At any temperature, pK_a decreased as the solvent was enriched with EtOH. The dissociation and transfer thermodynamic parameters were calculated, and the results showed that a non‐spontaneous free‐energy change (Δ_dissG^o>0) and unfavorable enthalpy (Δ_dissH^o>0) and entropy (Δ_dissS^o<0) changes occurred on dissociation of trazodone hydrochloride. The free‐energy change or pK_a varied nonlinearly with the reciprocal dielectric constant, indicating the inadequacy of the electrostatic approach. The dissociation equilibria are discussed on the basis of the standard thermodynamics of transfer, solvent basicity, and solute‐solvent interactions. The values of Δ_transG^o and Δ_transH^o increased negatively with increasing EtOH content, revealing a favorable transfer of trazodone hydrochloride from H₂O to EtOH/H₂O mixtures and preferential solvation of H⁺ and trazodone (TZD). Also, Δ_transS^o values were negative and reached a minimum, in the H₂O‐rich zone that has frequently been related to the initial promotion and subsequent collapse of the lattice structure of water. The pK_a or Δ_dissG^o values correlated well with the Dimroth‐Reichardt polarity parameter E_T(30), indicating that the physicochemical properties of the solute in binary H₂O/organic solvent mixtures are better correlated with a microscopic parameter than the macroscopic one. Also, it is suggested that preferential solvation plays a significant role in influencing the solvent dependence of dissociation of trazodone hydrochloride. The solute‐solvent interactions were clarified on the basis of the linear free‐energy relationships of Kamlet and Taft. The best multiparametric fit to the Kamlet‐Taft equation was evaluated for each thermodynamic parameter. Therefore, these parameters in any EtOH/H₂O mixture up to 80% were accurately derived by means of the obtained equations.     

An Approach to Mixed PnAsm Ligand Complexes

The reaction of a P₄ butterfly complex with yellow arsenic yields the largest mixed P_nAs_m ligand complexes synthesized to date. [{Cp′′′Fe(CO)₂}₂(μ,η^1:1‐P₄)] reacts with As₄ to yield [{Cp′′′Fe}₂(μ,η^4:4‐P_nAs_4‐n)] and [Cp′′′Fe(η⁵‐P_nAs_5‐n)]. Mass spectrometry together with NMR spectroscopy and X‐ray crystallography give clear evidence about the arrangement of the E positions within the cyclo‐E₅ and E₄ moieties of the products. Moreover, the results of DFT calculations agree well with the experimental determined outcomes. By coordinating the E₄ complex [{Cp′′′Fe}₂(μ,η^4:4‐P_nAs_4‐n)] with CuCl, a rearrangement of the E positions occurs in favor with a preferred phosphorus coordination towards copper atoms in the resulting 1D polymeric chain.     

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.     

Collisional energy transfer in highly vibrationally excited molecules: A very low-pressure pyrolysis study of acetyl chloride

The average downward energy transfer (〈Δ E_down〉) is obtained for highly vibrationally excited acetyl chloride with Ne and C₂H₄ bath gases at ca. 870 K. Data are obtained by the technique of very low-pressure pyrolysis (VLPP). Fitting these data by solution of the appropriate reaction-diffusion integrodifferential master equation yields the gas/gas collisional energy transfer parameters: 〈Δ E_down〉 values are 220 ± 10 cm^?1 (Ne bath gas) and 330 ± 20 cm^?1 (C₂H₄). These energy transfer quantities are much less than those predicted by statistical theories, or those observed for similar sized molecules such as CH₃CH₂Cl. These results are explained by the qualitative predictions of the biased random walk model wherein the fundamental mechanism of energy transfer is the multiple interactions between the bath gas and the individual atoms of the reactant molecule, during the course of the collision event. The charge distribution of acetyl chloride decreases the number of such interactions, thereby reducing the amount of energy transferred per collision.     

High‐Potential Perfluorinated Phthalocyanine–Fullerene Dyads for Generation of High‐Energy Charge‐Separated States: Formation and Photoinduced Electron‐Transfer Studies

High oxidation potential perfluorinated zinc phthalocyanines (ZnF_nPcs) are synthesised and their spectroscopic, redox, and light‐induced electron‐transfer properties investigated systematically by forming donor–acceptor dyads through metal–ligand axial coordination of fullerene (C₆₀) derivatives. Absorption and fluorescence spectral studies reveal efficient binding of the pyridine‐ (Py) and phenylimidazole‐functionalised fullerene (C₆₀Im) derivatives to the zinc centre of the F_nPcs. The determined binding constants, K, in o‐dichlorobenzene for the 1:1 complexes are in the order of 10⁴ to 10⁵ M ^?1; nearly an order of magnitude higher than that observed for the dyad formed from zinc phthalocyanine (ZnPc) lacking fluorine substituents. The geometry and electronic structure of the dyads are determined by using the B3LYP/6‐31G* method. The HOMO and LUMO levels are located on the Pc and C₆₀ entities, respectively; this suggests the formation of ZnF_nPc^.+–C₆₀Im^.? and ZnF_nPc^.+–C₆₀Py^.? (n=0, 8 or 16) intra‐supramolecular charge‐separated states during electron transfer. Electrochemical studies on the ZnPc–C₆₀ dyads enable accurate determination of their oxidation and reduction potentials and the energy of the charge‐separated states. The energy of the charge‐separated state for dyads composed of ZnF_nPc is higher than that of normal ZnPc–C₆₀ dyads and reveals their significance in harvesting higher amounts of light energy. Evidence for charge separation in the dyads is secured from femtosecond transient absorption studies in nonpolar toluene. Kinetic evaluation of the cation and anion radical ion peaks reveals ultrafast charge separation and charge recombination in dyads composed of perfluorinated phthalocyanine and fullerene; this implies their significance in solar‐energy harvesting and optoelectronic device building applications.     

Peptide o‐Aminoanilides as Crypto‐Thioesters for Protein Chemical Synthesis

Fully unprotected peptide o‐aminoanilides can be efficiently activated by NaNO₂ in aqueous solution to furnish peptide thioesters for use in native chemical ligation. This finding enables the convergent synthesis of proteins from readily synthesizable peptide o‐aminoanilides as a new type of crypto‐thioesters. The practicality of this approach is shown by the synthesis of histone H2B from five peptide segments. Purification or solubilization tags, which are sometimes needed to improve the efficiency of protein chemical synthesis, can be incorporated into the o‐aminoanilide moiety, as demonstrated in the preparation of the cyclic protein lactocyclicin Q.     

Probing the role of the linker in ferrocene-ATP conjugates: monitoring protein kinase catalyzed phosphorylations electrochemically

The synthesis and electrochemical properties of ferrocene conjugates are presented for the purpose of investigating adenosine 5′‐[γ‐ferrocenoylalkyl] triphosphate ( 1 a – 4 a , ferrocene (Fc)–ATP) as co‐substrates for phosphorylation reactions. Compounds 1 a – 4 a were synthesized, purified by HPLC, and characterized by NMR spectroscopy and mass spectrometry. In solution, all Fc–ATP bioconjugates exhibit a reversible one‐electron redox process with a half‐wave potential (E_1/2) in the 390–430 mV range, peak separations (ΔE_p) in the 40–70 mV range, and the peak current ratio (i_pa/i_pc) near unity. The peptide‐modified surface Glu‐Gly‐Ile‐Tyr‐Asp‐Val‐Pro was used to study the sarcoma‐related protein (Src) kinase activity by employing the Fc–ATP bioconjugates as co‐substrates. Subsequent kinase‐catalyzed transfer of the γ‐Fc‐phosphate group to the tyrosine residues of the surface‐bound peptides was characterized by a formal potential (E^o) ≈390 mV (vs. Ag/AgCl). The Fc‐coverage, estimated by time‐of‐flight secondary‐ion mass spectrometry (TOF‐SIMS) and cyclic voltammetry (CV), suggested validity of Fc–ATP conjugates as kinase co‐substrates. Depending on the length of the alkyl spacer of the Fc–ATP conjugate, different current densities were obtained, pointing to a direct correlation between the two. Molecular modeling revealed that the structural constraint imposed by the short alkyl spacer ( 1 a ) causes a steric congestion and negatively affects the outcome of phosphorylation reaction. An optimal analytical response was obtained with the Fc–ATP conjugates with linker lengths longer than six CH₂ groups.     

Electrospray ionization mass spectrometry of tributyltin(IV) complexes and their larvicidal activity on mosquito larvae: crystal and molecular structure of polymeric (Bu3Sn[O2CC6H4{NN(C6H3‐4‐OH(C(H)NC6H4OCH3‐4))}‐o])n

A series of tributyltin(IV) complexes of 2‐[(E)‐2‐(3‐formyl‐4‐hydroxyphenyl)‐1‐diazenyl]benzoic acid and 4‐[((E)‐1‐{2‐hydroxy‐5‐[(E)‐2‐(2‐carboxyphenyl)‐1‐diazenyl]phenyl}methylidene)amino]aryls have been investigated by electrospray mass spectrometry (ESI‐MS) and tandem mass spectrometry (MSⁿ) techniques. The assignments are facilitated by agreement between observed and calculated isotopic patterns and MSⁿ studies. Single‐crystal X‐ray crystallography of (Bu₃Sn[O₂CC₆H₄{N?N(C₆H₃‐4‐OH(C(H)?NC₆H₄OCH₃‐4))}‐o])_n reveals a polymeric structure. Toxicity studies of the tributyltin(IV) complexes of the 4‐[((E)‐1‐{2‐hydroxy‐5‐[(E)‐2‐(2‐carboxyphenyl)‐1‐diazenyl]phenyl}methylidene)amino]aryls on the second larval instar of the Aedes aegypti and Anopheles stephensi mosquito larvae are also reported. The LC₅₀ values indicate that the complexes are effective larvicides, which range from a low of 0.36 ppm to a high of 0.69 ppm against the Ae. aegypti larvae and between 0.82 and 1.17 ppm against the An. stephensi larvae. Copyright © 2005 John Wiley & Sons, Ltd.     

Inverse gas chromatography of lignocellulosic fibers coated with a thermosetting polymer: Use of peak maximum and conder and young methods

The Conder and Young (CY) and the peak maximum (PM) methods were used to estimate the retention time of n-alkane probes on chemithermomechanical pulp (CTMP) wood fibers treated with a low molecular weight grade phenol-formaldehyde resin (PFR). Thermodynamic functions (ΔH_a^o, ΔG_a^o, and ΔS_a^o) and the London dispersive component of the surface energy were derived from these retention times. Treated wood fibers show a high energy surface due to the presence of the thermoset resin on their surface. Values of ΔH_a^o obtained from the CY method were higher than those obtained with the PM method at relatively high temperatures and with relatively low molecular weight alkanes. The results from the two methods were identical at low temperature (293 K) and with the relatively high molecular weight alkane n-undecane.     

Synthesis of poly(n‐butyl acrylate) homopolymer and poly(styrene‐b‐n‐butyl acrylate‐b‐styrene) triblock copolymer via AGET emulsion ATRP using a cationic surfactant

Cationic emulsions of triblock copolymer particles comprising a poly(n‐butyl acrylate) (PⁿBA) central block and polystyrene (PS) outer blocks were synthesized by activator generated by electron transfer (AGET) atom transfer radical polymerization (ATRP). Difunctional ATRP initiator, ethylene bis(2‐bromoisobutyrate) (EBBiB), was used as initiator to synthesize the ABA type poly(styrene‐b‐n‐butyl acrylate‐b‐styrene) (PS‐PⁿBA‐PS) triblock copolymer. The effects of ligand and cationic surfactant on polymerizations were also discussed. Gel permeation chromatography (GPC) was used to characterize the molecular weight (M_n) and molecular weight distribution (MWD) of the resultant triblock copolymers. Particle size and particle size distribution of resulted latexes were characterized by dynamic light scattering (DLS). The resultant latexes showed good colloidal stability with average particle size around 100–300 nm in diameter. Glass transition temperature (T_g) of copolymers was studied by differential scanning calorimetry (DSC). © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 611–620     

Lanthanide(III) Complexes with Two Hexapeptides Incorporating Unnatural Chelating Amino Acids: Secondary Structure and Stability

Unnatural metal‐chelating amino acids bearing aminodiacetate side‐chains have been introduced into two hexapeptides to obtain efficient lanthanide‐binding peptides. The synthesis of the enantiopure Fmoc‐Ada_n(tBu)₂‐OH synthons is described with overall yields of 32 and 50 % for n=2 and n=3 side‐chain carbon atoms, respectively. The two peptides AcWAda_nPGAda_nGNH₂ ( P ⁿ ) were synthesized from the protected synthons by standard solid‐phase peptide synthesis. Studies of the lanthanide complexes of the two peptides P ⁿ by luminescence titrations, mass spectrometry, circular dichroism, and solution NMR spectroscopy demonstrate that the Ada_n chain length has a dramatic effect on the complexation properties. Indeed, the flexible compound P³ forms a mononuclear complex of moderate stability (β₁₁=10^9.9), which tends to transform into a binuclear species in the presence of excess of the metal ion. Interestingly, the more compact peptide P² provides stable Ln³⁺ complexes with the exclusive formation of the mononuclear Ln P² adduct. The stability constant of Tb P² is two orders of magnitude higher (β₁₁=10^12.1) than that measured for P³ . The 800 MHz NMR spectrum of the La³⁺ complex of P² evidences a well‐defined type II β‐turn as well as a hydrophobic Trp(indole)–Pro interaction. These interactions exemplify the non‐innocent character of the peptide spacer in the complex La P² as well as the role of a peptide secondary structure in the stabilization of metal complexes.     

Fragmentation and reaction processes in cluster-surface collisions

We review the processes which have been observed from collisions between alkali-halide clusters and solid surfaces. Soft impact of nanocrystalline Na_nF _n?1 ⁺ clusters against solid surfaces causes them to cleave along the lowest energy (100) plane. At higher collision energies (E_i>1 eV/atom), an evaporative cascade occurs which is characteristic of a transformation of the nanocrystal to a molten state. Efficient F^? transfer from the cluster to the surface can occur for the larger clusters (>60 atoms) scattering from Si(111), in direct competition with the cleaving channel at low energies. In this regime, strong bonds can form between the F^? and silicon surface. The reaction probability increases with cluster size indicating that an impact-initiated shock wave is needed to enhance the reactive process.     

Gas‐phase dissociation of ionic liquid aggregates studied by electrospray ionisation mass spectrometry and energy‐variable collision induced dissociation

Positive singly charged ionic liquid aggregates [(C_nmim)_m+1(BF₄)_m]⁺ (mim = 3‐methylimidazolium; n = 2, 4, 8 and 10) and [(C₄mim)_m+1(A)_m]⁺ (A = Cl⁻, BF₄⁻, PF₆⁻, CF₃SO₃⁻ and (CF₃SO₂)₂N⁻) were investigated by electrospray ionisation mass spectrometry and energy‐variable collision induced dissociation. The electrospray ionisation mass spectra (ESI‐MS) showed the formation of an aggregate with extra stability for m = 4 for all the ionic liquids with the exception of [C₄mim][CF₃SO₃]. ESI‐MS‐MS and breakdown curves of aggregate ions showed that their dissociation occurred by loss of neutral species ([C_nmim][A])_a with a ≥ 1. Variable‐energy collision induced dissociation of each aggregate from m = 1 to m = 8 for all the ionic liquids studied enabled the determination of E_{cm, 1/2} values, whose variation with m showed that the monomers were always kinetically much more stable than the larger aggregates, independently of the nature of cation and anion. The centre‐of‐mass energy values correlate well with literature data on ionic volumes and interaction and hydrogen bond energies. Copyright © 2008 John Wiley & Sons, Ltd.