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Jeanine Tortajada

Publications and source records attributed to Jeanine Tortajada.

At least 19 recordsLinked to original sources
PubMed2007

Unimolecular reactivity of uracil-Cu(2+) complexes in the gas phase.

The gas-phase interaction of copper(II) ions with uracil are studied by means of mass spectrometry and B3LYP/6-311+G(2df,2p)//B3LYP/6-31G(d) calculations. Positive-ion electrospray spectra show that the reaction of uracil with copper(II) gives rise to singly charged species, whereby the [Cu(uracil--H)](+) complex is the most intense ion in the spectra at low concentration. Mass spectrometry/mass spectrometry (MS/MS) experiments show that the loss of HNCO and NCO are the dominant fragmentation processes, accompanied by a minor loss of CO. A systematic study of the spectra obtained with different labeled species, namely, 2-(13)C- (m/z 175), 2-(13)C,1,3-(15)N(2)- (m/z 177) and 3-(15)N-uracil (m/z 175), concludes unambiguously that both the loss of HNCO and NCO involve exclusively C2 and N3, whereas only C4 is involved in the loss of CO. Suitable mechanisms for these fragmentation processes are proposed through a theoretical survey of the corresponding potential energy surface. In these mechanisms, pi complexes, which lie high in energy with respect to the global minimum, play a significant role in the loss of NCO; this explains why both products, HNCO and NCO involve the same atoms of the ring.

Journal Article↗
PubMed2006

A coupled Car-Parrinello molecular dynamics and EXAFS data analysis investigation of aqueous Co(2+).

We have studied the microscopic solvation structure of Co(2+) in liquid water by means of density functional theory (DFT)-based Car-Parrinello molecular dynamics (CPMD) simulations and extended X-ray absorption fine structure (EXAFS) data analysis. The effect of the number of explicit water molecules in the simulation box on the first and second hydration shell structures has been considered. Classical molecular dynamics simulations, using an effective two-body potential for Co(2+)-water interactions, were also performed to show box size effects in a larger range. We have found that the number of explicit solvent molecules has a marginal role on the first solvation shell structural parameters, whereas larger boxes may be necessary to provide a better description of the second solvation shell. Car-Parrinello simulations were determined to provide a reliable description of structural and dynamical properties of Co(2+) in liquid water. In particular, they seem to describe both the first and second hydration shells correctly. The EXAFS signal was reconstructed from Car-Parrinello simulations. Good agreement between the theoretical and experimental signals was observed, thus strengthening the microscopic picture of the Co(2+) solvation properties obtained using first-principle simulations.

Cations, Divalent↗
PubMed2006

A study of noncovalent complexes involving single-stranded DNA and polybasic compounds using nanospray mass spectrometry.

Noncovalent complexes involving a single-stranded DNA oligonucleotide and a polybasic compound (spermine, penta-L-lysine, penta-L-arginine, or polydisperse poly-L-lysine) were detected by nanospray-MS. Several control experiments tended to show that these complexes preexisted in solution and that the interactions were initially ionic ones between oligonucleotide phosphates and protonated basic sites of the polybasic compound. Collision-induced dissociation (CID) experiments carried out with these complexes allowed us to identify some differences in the nature of the interactions between the solution and the gas phase, arising from possible proton transfers. Different dissociation pathways were observed according to the nature of the polybasic compound and to the initial charge state of the complex. The complex involving spermine dissociated by cleavage of noncovalent bonds leading to the separation of the two components, whereas the one involving penta-L-arginine underwent fragmentations of covalent bonds. Both behaviors were independent of the initial charge state of the complex. On the other hand, the dissociation pathway of the complex involving penta-L-lysine has been shown to be clearly charge state dependent. Noncovalent dissociation (separation of the two components) driven by coulomb repulsion occurred for the higher charged complexes, whereas fragmentation of covalent bonds was the main pathway of the lower charged complexes. In the latter case, differences in CID behavior were observed for different lengths of poly-L-lysine.

Biogenic Polyamines↗
PubMed2006

An experimental and theoretical investigation of gas-phase reactions of Ca2+ with glycine.

The gas-phase reactions between Ca(2+) and glycine ([Ca(gly)](2+)) have been investigated through the use of mass spectrometry techniques and B3-LYP/cc-pWCVTZ density functional theory computations. The major peaks observed in the electrospray MS/MS spectrum of [Ca(gly)](2+) correspond to the formation of the [Ca,C,O(2),H](+), NH(2)CH(2) (+), CaOH(+), and NH(2)CH(2)CO(+) fragment ions, which are produced in Coulomb explosion processes. The computed potential energy surface (PES) shows that not only are these species the most stable product ions from a thermodynamic point of view, but they may be produced with barriers lower than for competing processes. Carbon monoxide is a secondary product, derived from the unimolecular decomposition of some of the primary ions formed in the Coulomb explosions. In contrast to what is found for the reactions of Ca(2+) with urea ([Ca(urea)](2+)), minimal unimolecular losses of neutral fragments are observed for the gas-phase fragmentation processes of [Ca(gly)](2+), which is readily explained in terms of the topological differences between their respective PESs.

Calcium↗
PubMed2006

Co2+ binding cysteine and selenocysteine: a DFT study.

In this paper we report structural and energetic data for cysteine and selenocysteine in the gas phase and the effect of Co(2+) complexation on their properties. Different conformers are analyzed at the DFT/B3LYP level of both bound and unbound species. Geometries, vibrational frequencies, and natural population analysis are reported and used to understand the activity of these species. In particular, we have focused our attention on the role of sulfur and selenium in the metal binding process and on the resulting deprotonation of the thiol and seleniol functions. From the present calculations we are able to explain, both from electronic structure and thermochemical point of views, a metal-induced thiol deprotonation as observed in gas-phase experiments. A similar process is expected in the case of selenocysteine. In fact, cobalt was found to have a preferential affinity with respect to thiolate and selenolate functions. This can be related to the observation that only S and Se are able-in thiolate and selenolate states-to make a partial charge transfer to the cobalt thus forming very stable complexes. Globally, very similar results are found when substituting S with Se, and a very small difference in cobalt binding affinity is found, thus justifying the use of this substitution in X-ray absorption experiments done on biomolecules containing cysteine metal binding pockets.

Cations, Divalent↗
PubMed2006

Toward a DFT-based molecular dynamics description of Co(II) binding in sulfur-rich peptides.

In this paper, we investigated the reliability of a Car-Parrinello molecular dynamics (CPMD) approach to characterize the binding of Co(II) metal cation to peptide molecules containing cysteine. To this end, we compared pseudo-potentials and DFT plane wave expansion, which are used as key ingredients in the CPMD method, with standard all-electron Gaussian basis set DFT calculations. The simulations presented here are the first attempts to characterize interactions and dynamics of Co(II) metal with the building blocks of phytochelatin peptide molecules. Benchmark calculations are performed on [Co(Cys-H)]+ and [Co(Glutathione-H)]+ complexes, since they are the main fragments of the Co(II)-Cys and Co(II)-glutathione systems found in gas phase electrospray ionisation mass spectrometry (ESI-MS) experiments done in our laboratory. We also present benchmark calculations on the [Co(H2O)6)]2+ cluster with direct comparisons to highly correlated ab initio calculations and experiments. In particular, we investigated the dissociation path of one water molecule from the first hydration shell of Co(II) with CPMD. Overall, our molecular dynamics simulations shed some light on the nature of the Co(II) interaction and reactivity in Co(II)-phytochelatin building block systems related to the biological and environmental activity of the metal, either in the gas or liquid phase.

Cobalt↗
PubMed2006

Block lengths and block sequence of linear triblock and glycerol derivative diblock copolyethers by electrospray ionization--collision-induced dissociation mass spectrometry.

Chemical properties of ethylene oxide (EO) and propylene oxide (PO) block copolymers are strongly dependent on their sequence. Useful information about copolymer sequence can be obtained by tandem mass spectrometry (MS/MS). In this work, collision-induced dissociation (CID) of ammonium adducts of various linear triblock and glycerol derivative diblock copolyethers produced by electrospray ionization was studied under low-energy conditions. At first, homopolymers MS/MS spectra enabled us to identify the nature of the product ions and to suggest decomposition pathways. Then, it was shown that copolyethers with the same composition in each repeat unit but with inversed block sequences (i.e., PEO-b-PPO-b-PEO vs PPO-b-PEO-b-PPO and gPEO-b-PPO vs gPPO-b-PEO) can be easily distinguished with characteristic fragment ions. In the case of linear copolymers, CID spectra gave pertinent information about block lengths.

Epoxy Compounds↗
PubMed2006

Gas-phase deprotonation of uracil-Cu2+ and thiouracil-Cu2+ complexes.

The deprotonation of Cu2+ complexes with uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil has been investigated by means of B3LYP/ 6-311+G(2df,2p)//6-31G(d) calculations. The most stable [(uracil-H)Cu]+ and [(thiouracil-H)Cu]+ complexes correspond to bidentate structures in which Cu interacts with the deprotonated ring-nitrogen atom and with the oxygen or the sulfur atom of the adjacent carbonyl or thiocarbonyl group. For 2- and 4-thiouracil derivatives, the structures in which the metal cation interacts with the thiocarbonyl group are clearly favored with respect to those in which Cu interacts with the carbonyl group. This is at variance with what was found to be the most stable structure of the corresponding Cu2+ complexes, where association to the carbonyl oxygen was always preferred over the association to the thiocarbonyl group. The [(uracil-H)Cu]+ and [(thiouracil-H)Cu]+ complexes can be viewed as the result of Cu+ attachment to the uracil-H and thiouracil-H radicals formed by the deprotonation of the corresponding uracil+* and thiouracil+* radical cations. As a matter of fact their relative stability is dictated by the intrinsic stability of the corresponding uracil-H and thiouracil-H radical and by the fact that, in general, the N3-deprotonated site is a better electron donor than the N1. In all complexes, the bonding of Cu both to nitrogen and sulfur and to nitrogen and oxygen has a significantly large covalent character.

Binding Sites↗
PubMed2005

Analysis of poly(oxyethylene) and poly(oxypropylene) triblock copolymers by MALDI-TOF mass spectrometry.

Triblock copolymers of ethylene oxide (EO) and propylene oxide (PO) are widely used in the chemical industry as nonionic surfactants. Triblock copolymers can be arranged in a EO-PO-EO or PO-EO-PO sequence. This arrangement results in an amphiphilic copolymer, in which the block sequence and block length determine the properties of the copolymer. MALDI-TOF MS was used to analyze various triblock copolyethers: EO-PO-EO (Mn =2000 g.mol(-1)), PO-EO-PO (Mn = 2000 g.mol(-1)), and a random copolymer EO/PO (Mn = 2500 g.mol(-1)). Data treatment was assisted by using a homemade software allowing a picture of monomer composition of oligomers from the mass spectra. MALDI-TOF mass spectra of EO/PO copolymers were shown to depend strongly on the number of laser shots, relative proportions of polymer/salt, and the nature of the matrix. An unsaturated byproduct was detected. Its presence was demonstrated by prefractionation of copolymers by SEC before MALDI-TOF analysis, and its content was estimated by 1H NMR. The formation of layers inside the MALDI deposit was evidenced by varying the number of laser shots. Lighter oligomers of the copolymer, unsaturated byproduct, or both would be in the core of the deposit, coated with heavier oligomer. The layer formation depends on the nature of the matrix and the quantity of added salt. DHB matrix with a relative high sodium salt content induces layer formation inside the deposit, whereas dithranol matrix or low salt content does not. Consequently, an optimization of experimental parameters in order to estimate the lighter oligomers or unsaturated byproduct content or to obtain the actual representation of the monomer contribution in the copolymers from the MS data only seems obviously critical. MALDI-TOF mass spectrometry is obviously a powerful technique to analyze copolymers, but a careful survey of the experimental parameters is required. The combination of MALDI-TOF MS with separations techniques and NMR brings precious complementary information.

Anthralin↗
PubMed2005

CD98, a novel marker of transient amplifying human keratinocytes.

Identification of plasma membrane markers of basal keratinocytes is essential for sorting basal cells and, subsequently, adult epidermal stem cells. In this study, we isolated caveolin-1-enriched microdomains from human HaCaT keratinocytes and identified proteins representing potential cell surface markers of the epidermis by a proteomic approach. The purification of this caveolae domain allowed us to characterize 53 proteins of which 26% were transmembrane and 32% associated-membrane proteins. One of them, CD98, was found to be co-localized with beta1 integrin at the plasma membrane of the basal keratinocytes of healthy human epidermis. We then isolated CD98-positive keratinocytes from fresh skin biopsies. Using clonogenic assays, we demonstrate that CD98 may be considered as a marker of transient amplifying human keratinocytes.

Caveolin 1↗
PubMed2004

Association of Cu2+ with uracil and its thio derivatives: a theoretical study.

The structures and relative stabilities of the complexes between Cu2+ and uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil were investigated by B3LYP/6-311+G(2df,2p)//B3LYP/6-31G* DFT calculations. In those systems in which both types of basic centers, that is, a carbonyl and a thiocarbonyl group, are present, association of Cu2+ with the oxygen atom is systematically favored, in contrast to what was found for the corresponding Cu+ complexes. This can be understood by considering that association of Cu2+ is immediately followed by oxidation of the base, which accumulates the negative charge at the oxygen atoms. Similarly, for 2,4-dithiouracil the most basic site for Cu+ attachment is the sulfur atom at the 4-position, while for association of Cu2+ it is sulfur at the 2-position. In contrast, differences between uracil-Cu+ and uracil-Cu2+ complexes are very small, and in both cases the oxygen atom at the 4-position is the most basic. Cu2+ binding energies are about 4 and 1.2 times larger than Cu+ binding energies and proton affinities, respectively. Uracil- and thiouracil-Cu2+ complexes are thermodynamically unstable but kinetically stable with respect to their dissociation into uracil*+ + Cu+ or thiouracil*+ + Cu+. The Cu2+ binding energies vary with the difference between the second ionization potential of the metal and the first ionization potential of the base. regardless of the reference acid (H+, Cu+, Cu2+) the basicity trend is 2,4-dithiouracil > 4-thiouracil > 2-thiouracil > uracil.

Cations↗
PubMed2004

Unimolecular reactivity of strong metal-cation complexes in the gas phase: ethylenediamine-Cu(+).

The gas-phase reactions between ethylenediamine (en) and Cu(+) have been investigated by means of mass spectrometry techniques. The MIKE spectrum reveals that the adduct ions [Cu(+)(H(2)NCH(2)CH(2)NH(2))] spontaneously decompose by loosing H(2), NH(3) and HCu, the loss of hydrogen being clearly dominant. The spectra of the fully C-deuterated species show the loss of HD, NH(3) and CuD but no losses of H(2), D(2), NH(2)D, NHD(2), ND(3) or CuH are observed. This clearly excludes hydrogen exchange between the methylene and the amino groups as possible mechanisms for the loss of ammonia. Conversely, methylene hydrogen atoms are clearly involved in the loss of molecular hydrogen. The structures and bonding characteristics of the Cu(+)(en) complexes as well as the different stationary points of the corresponding potential energy surface (PES) have been theoretically studied by DFT calculations carried out at B3LYP/6-311+G(2df,2p)//B3LYP/6-311G(d,p) level. Based on the topology of this PES the most plausible mechanisms for the aforementioned unimolecular fragmentations are proposed. Our theoretical estimates indicate that Cu(+) strongly binds to en, by forming a chelated structure in which Cu(+) is bridging between both amino groups. The binding energy is quite high (84 kcal mol(-1)), but also the products of the unimolecular decomposition of Cu(+)(en) complexes are strongly bound Cu(+)-complexes.

Journal Article↗
PubMed2004

Characterization of peptides by liquid chromatography/electrospray ionization mass spectrometry using silver nitrate as a post-column complexant.

Two model peptides, des-Arg1-bradykinin (DAB) and bradykinin (B), were cationized by Ag+ after their separation by reversed-phase liquid chromatography (RPLC) prior to mass spectrometry (MS). Silver nitrate solution was used as a post-column reagent. The RPLC and MS experimental conditions were optimized using flow injection in order to obtain sufficiently abundant silver adducts to permit MS/MS experiments. The use of water-methanol with 0.1% formic acid as mobile phase allowed a good chromatographic separation of the two peptides with a polymeric stationary phase and sufficiently abundant silver-containing adducts, [M + Ag + H]2+ and [M + 2Ag]2+. The gas-phase dissociation of [DAB + Ag + H]2+ and [DAB + 2Ag]2+ led to interpretable mass spectra during the on-line cationization experiment. Most of the ions obtained by dissociating [DAB + Ag + H]2+ and [DAB + 2Ag]2+ species are silver-containing ions but the ions produced depend on the parent. The ions coming from the dissociation of the doubly charged silver adducts [DAB + Ag + H]2+ or [DAB + 2Ag]2+ are of interest compared with those coming from the singly charged silver species or doubly charged protonated species. The fragmentation of the doubly charged silver adducts provides ions over the entire mass range. Although the presence of several prolines in des-Arg1-bradykinin prevents the formation of some expected ions, the observation of triplets [an-H + Ag]+, [bn-H + Ag]+ and [bn + OH + Ag]+ produced by the dissociation of on-line Ag(+)-cationized peptides could contribute to greater success of automatic sequencing of peptides.

Bradykinin↗
PubMed2004

Gas-phase acidity of D-glucose. A density functional theory study.

The gas-phase acidity of D-glucopyranose was studied by means of B3LYP calculations combined with 6-31G(d,p) or 6-31+G(d,p) standard basis sets. For each anomer, deprotonation of the various primary and secondary hydroxyl groups was considered. As in solution, the anomeric hydroxyl is found to be the most acidic for both anomers, but only when the 6-31+G(d,p) basis set is used for geometry optimization. Deprotonation of the anomeric hydroxyl induces an important C(1)--O endocyclic bond elongation and subsequently promotes an energetically favored ring-opening process as attested by the very small calculated activation barriers. The results also suggest that interconversion between the various deprotonated alpha- and beta-anomers may easily occur under slightly energetic conditions. B3LYP/6-311+G(2df,2p) calculations led to the an absolute gas-phase acidity of deltaacidGo(298)(alpha-D-glucose) = 1398 kJ mol(-1). This estimate matches well the only experimental value available to date. Finally, this study again confirms that the use of diffuse functions on heavy atoms is necessary to describe anionic systems properly and to achieve good relative and absolute gas-phase acidities.

Gases↗
PubMed2003

Identification of water-soluble selenium-containing proteins in selenized yeast by size-exclusion-reversed-phase HPLC/ICPMS followed by MALDI-TOF and electrospray Q-TOF mass spectrometry.

An approach to speciation of selenium incorporated in yeast proteins was developed. The tryptic digest of a water-soluble protein fraction isolated by size-exclusion chromatography was analyzed by reversed-phase HPLC/ICPMS. The selenopeptides selected owing to the detector's elemental specificity were then analyzed by MALDI-TOFMS in order to select target ions for collision-induced dissociation MS. The latter, carried out with an electrospray Q-TOF spectrometer, enabled the sequencing of the selenopeptides detected by HPLC/ICPMS. The approach allowed for the first time the identification of a family of Se-containing proteins resulting from the replacement by selenomethionine of 2-9 methionine residues in a salt-stress-induced protein SIP18 (Mr 8874). The presence of these proteins was confirmed by MALDI-TOFMS of the original (nondigested) protein fraction. Another selenium protein identified was a heat-shock protein HSP12 (Mr 11693) in which the only methionine residue was replaced by selenomethionine. These two Se-containing proteins accounted for more than 95% of selenium in the water-soluble protein fraction.

Amino Acid Sequence↗
PubMed2003

MALDI/MS peptide mass fingerprinting for proteome analysis: identification of hydrophobic proteins attached to eucaryote keratinocyte cytoplasmic membrane using different matrices in concert.

BACKGROUND: MALDI-TOF-MS has become an important analytical tool in the identification of proteins and evaluation of their role in biological processes. A typical protocol consists of sample purification, separation of proteins by 2D-PAGE, enzymatic digestion and identification of proteins by peptide mass fingerprint. Unfortunately, this approach is not appropriate for the identification of membrane or low or high pI proteins. An alternative technique uses 1D-PAGE, which results in a mixture of proteins in each gel band. The direct analysis of the proteolytic digestion of this mixture is often problematic because of poor peptide detection and consequent poor sequence coverage in databases. Sequence coverage can be improved through the combination of several matrices. RESULTS: The aim of this study was to trust the MALDI analysis of complex biological samples, in order to identify proteins that interact with the membrane network of keratinocytes. Peptides obtained from protein trypsin digestions may have either hydrophobic or hydrophilic sections, in which case, the direct analysis of such a mixture by MALDI does not allow desorbing of all peptides. In this work, MALDI/MS experiments were thus performed using four different matrices in concert. The data were analysed with three algorithms in order to test each of them. We observed that the use of at least two matrices in concert leads to a twofold increase of the coverage of each protein. Considering data obtained in this study, we recommend the use of HCCA in concert with the SA matrix in order to obtain a good coverage of hydrophilic proteins, and DHB in concert with the SA matrix to obtain a good coverage of hydrophobic proteins. CONCLUSION: In this work, experiments were performed directly on complex biological samples, in order to see systematic comparison between different matrices for real-life samples and to show a correlation that will be applicable to similar studies. When 1D gel is needed, each band may contain a great number of proteins, each present in small amounts. To improve the proteins coverage, we have performed experiments with some matrices in concert. These experiments enabled reliable identification of proteins, without the use of Nanospray MS/MS experiments.

Journal Article↗
PubMed2003

Detection of selenocompounds in a tryptic digest of yeast selenoprotein by MALDI time-of-flight MS prior to their structural analysis by electrospray ionization triple quadrupole MS.

MALDI-TOFMS was proposed as a key technique to a novel generic approach for the speciation analysis of selenium in yeast supplements. Owing to a lower detection limit and superior matrix tolerance to electrospray MS it allowed a successful detection of selenocompounds in samples for which electrospray MS had failed. The analytical approach developed was applied to the identification of a previously unreported selenopentapeptide (m/z 596) in the tryptic digest of a water-soluble selenoprotein fraction isolated by size-exclusion chromatography. The information on the mass of the protonated molecular ion obtained from MALDI allowed the optimization of the conditions for collision induced dissociation MS using a triple quadrupole spectrometer that enabled the determination of the amino acid sequence SeMet-Asn-Ala-Gly-Arg of the selenopeptide.

Dietary Supplements↗
PubMed2003

The gas-phase basicity and proton affinity of 1,3,5-cycloheptatriene--energetics, structure and interconversion of dihydrotropylium ions.

The hitherto unknown gas-phase basicity and proton affinity of 1,3,5-cycloheptatriene (CHT) have been determined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Several independent techniques were used in order to exclude ambiguities due to proton-induced isomerisation of the conjugate cyclic C(7)H(9)(+) ions, [CHT + H](+). The gas-phase basicity obtained by the thermokinetic method, GB(CHT) = 799 +/- 4 kJ mol(-1), was found to be identical, within the limits of experimental error, with the values measured by the equilibrium method starting with protonated reference bases, and with the values resulting from the measurements of the individual forward and reverse rate constants, when corrections were made for the isomerised fraction of the C(7)H(9)(+) population. The experimentally determined gas-phase basicity leads to the proton affinity of cycloheptatriene, PA(CHT) = 833 +/- 4 kJ mol(-1), and the heat of formation of the cyclo-C(7)H(9)(+) ion, deltaH(f)(0)([CHT + H](+)) = 884 +/- 4 kJ mol(-1). Ab initio calculations are in agreement with these experimental values if the 1,2-dihydrotropylium tautomer, [CHT + H((1))](+), generated by protonation of CHT at C-1, is assumed to be the conjugate acid, resulting in PA(CHT) = 825 +/- 2 kJ mol(-1) and deltaH(f)(0)(300)([CHT + H((1))](+)) = 892 +/- 2 kJ mol(-1). However, the calculations indicate that protonation of cycloheptatriene at C-2 gives rise to transannular C-C bond formation, generating protonated norcaradiene [NCD + H](+), a valence tautomer being 19 kJ mol(-1) more stable than [CHT + H((1))](+). The 1,4-dihydrotropylium ion, [CHT + H((3))](+), generated by protonation of CHT at C-3, is 17 kJ mol(-1) less stable than [CHT + H((1))](+). The bicyclic isomer [NCD + H](+) is separated by relatively high barriers, 70 and 66 kJ mol(-1) from the monocyclic isomers, [CHT + H((1))](+) and [CHT + H((3))](+), respectively. Therefore, the initially formed 1,2-dihydrotropylium ion [CHT + H((1))](+) does not rearrange to the bicyclic isomer [NCD + H](+) under mild protonation conditions.

Journal Article↗