l-Alanylglycylhistamine dihydro-chloride.

In the title compound {systematic name: 4-[2-({N-[(2S)-2-ammonio-propano-yl]glyc-yl}amino)-eth-yl]-1H-imidazol-3-ium dichloride}, C(10)H(19)N(5)O(2) (2+)·2Cl(-), the pseudo-tripeptide l-alanyl-glycyl-histamine is protonated at both the terminal amino group and the histidine N2 atom. The resulting positive charges are neutralized by two chloride anions. In the crystal, the organic cation adopts a twisted conformation about the CH(2)-CH(2) bond of histamine and about the C-N bond in the main chain, stabilized by a short intra-molecular C-H⋯O contact. In the crystal, N(+)-H⋯O and N(+)-H⋯Cl(-) hydrogen bonds link the mol-ecules into infinite sheets parallel to the (100) plane. The stacking of these sheets along the a axis is supported by N(amide)-H⋯Cl(-) hydrogen bonds.

The role of terminal amino group and histidine at the fourth position in the metal ion binding of oligopeptides revisited: Copper(II) and nickel(II) complexes of glycyl-glycyl-glycyl-histamine and its N-Boc protected derivative.

Copper(II) and nickel(II) binding properties of two pseudo tetrapeptides, N-Boc-Gly-Gly-Gly-Histamine (BGGGHa) and Gly-Gly-Gly-Histamine (GGGHa) have been investigated by pH-potentiometric titrations, UV-visible-, EPR-, NMR- and ESI-HRMS (electrospray ionization high resolution MS) spectroscopies, in order to compare the role of N-terminal amino group and imidazole moiety at the fourth position in the complex formation processes. Substantially higher stabilities were determined for the ML complexes of GGGHa, compared to those of BGGGHa, supporting the coordination of the terminal amino group and the histamine imidazole of the non-protected ligand. A dimeric Cu(2)H(-2)L(2) species, formed through the deprotonation of peptide groups of the ligands, was found in the GGGHa-copper(II) system. Deprotonation and coordination of further amide nitrogens led to CuH(-2)L and, above pH~10, CuH(-3)L. Experimental data supports a {NH(2), 2 × N(amide),N(im)} macrochelate structure in CuH(-2)L whereas a {NH(2), 3 × N(amide)} coordination environment in CuH(-3)L. The first two amide deprotonation processes were found to be strongly cooperative with nickel(II) and spectroscopic studies proved the transformation of the octahedral parent complexes to square planar, yellow, diamagnetic species, NiH(-2)L and above pH~9, NiH(-3)L. In the basic pH-range deprotonation and coordination of the amide groups also took place in the BGGGHa containing systems, leading to complexes with a {3 × N(amide),N(im)} donor set, and in parallel the re-dissolving of precipitate. Above pH~11, a further proton release from the pyrrolic NH group of the imidazole ring of BGGGHa occurred providing an additional proof for the different binding modes of the two ligands.

Nickel(II)-dipeptidoamine-based tetrameric complex: structural study in solution and in solid state.

The coordination structure of M(4)L(4)H(-8) macromolecules (M = Ni(II), Cu(II), Pd(II)) containing small peptidic ligands (L = Xaa-His or Xaa-His-Yaa) has been predicted primarily on the basis of spectroscopic and potentiometric data in the literature. In this work, the neutral tetranuclear nickel(II) complex 1 formed with four double-deprotonated ligands (L = α-methyl-alanyl-histamine) was prepared, and its crystal structure was determined (C(36)H(56)N(16)Ni(4)O(4)·4.5CH(3)OH·1.5H(2)O: a = 11.2645(4) A, b = 23.5003(8) A, c = 20.9007(7) A, ß = 102.321(1)°, monoclinic, P2(1)/c, Z = 4). In complex 1, the metal ions have a square planar geometry with 4N donor set consisting of the N-terminal amino nitrogen, the deprotonated amide nitrogen, the imidazole N(3) atom, and the deprotonated imidazole N(1) atom of the adjacent ligand. The latter nitrogen atom provides the connection of the four NiLH(-2) units forming a C(1) symmetrical saddle-like shape. The complexation of L with Ni(II) ion has been studied by a potentiometric method combined with UV-visible spectrophotometric titration. At pH 8.0, the predominant species is M(4)L(4)H(-8) with pK(4)(oligomerization) = 5.73. The tetranuclear structure of complex 1 was also studied in solution by (1)H and (13)C NMR spectroscopy suggesting a structure of symmetry S(4). DFT calculations on optimized structure in symmetry C(1) and S(4) have been performed to explain the observed differences in solution and in solid state. The nuclearity was also confirmed in solution by ESI-HRMS analysis.

Complexation of Cu(II) by original tartaric acid-based ligands in nonionic micellar media: thermodynamic study and applications.

The complexation of Cu(II) with original alkylamidotartaric acids (C(x)T) is investigated in homogeneous aqueous medium and in the presence of nonionic micelles of Brij 58 (C16EO20), thanks to various analytical techniques such as NMR self-diffusion experiments, CD and UV-vis spectroscopy, ESI mass spectrometry, pHmetry and micellar-enhanced ultrafiltration (MEUF). First, a complete speciation study proves the formation of dimeric complexes in water and provides their formation constants. Second, a similar study is led in the presence of nonionic micelles. It underlines a modification of the apparent equilibrium constants in micellar medium and demonstrates that the structure of the complexes is slightly modified in the presence of micelles. This thermodynamic and structural study is applied to modelize the evolution of the extraction yields of Cu(II) by the micelles as a function of pH and to identify the complexes extracted in the micelles. The effects of the chain length of the ligand (C3T vs C8T) on the solubilization properties are put into relief and discussed. Anionic species are proved to be more incorporated in the nonionic micelles than the cationic species. The extracting system constituted of octylamidotartaric acid (CsT) solubilized in nonionic micelles of Brij 58 is demonstrated to be very efficient for the extraction of Cu(II) by MEUF, this technique being an interesting green alternative to traditional solvent extraction.

4-{2-[3-(2-Ammonioacetamido)propanamido]ethyl}-1H-imidazol-3-ium dichloride.

Mol-ecules of the title compound, Gly-ß-Ala-Histamine dihydro-chloride, C(10)H(19)N(5)O(2) (2+)·2Cl(-), are linked by N-H⋯O and N-H⋯Cl hydrogen bonds into two-dimensional polymeric sheets parallel to the (011) plane, forming a stacked structure along the a axis. The parallel layers are also inter-linked alternately by different N-H⋯Cl hydrogen bonds, forming a three-dimensional framework.

Solubilization of amphiphilic carboxylic acids in nonionic micelles: determination of partition coefficients from pKa measurements and NMR experiments.

The solubilization of octylamidotartaric acid (C8T) and octanoic acid (C8C) in Triton X-100 and Brij 58 nonionic micelles has been studied by pHmetric and 1H NMR self-diffusion experiments. As both C8C and C8T exhibit acid-base properties, a distinction between the partition of the neutral acidic form, in terms of the partition coefficient KPH, and the partition of the charged basic form, in terms of the partition coefficient KP-, has been made. The acidity constants, Ka, of C8T and C8C in the presence of micelles have been evaluated from pHmetric experiments. For both solutes, an increase in the pKa is observed in micellar media due to the difference in the partition of acidic and basic forms of the solutes. A model has been developed to determine KPH and KP- from the pKa shifts observed. The values obtained by this pKa shift modeling method and those from self-diffusion coefficient measurements are in good agreement. The acidic form of C8C is incorporated to a larger extent into the Brij 58 micelles than the acidic form of C8T, whereas the opposite trend is observed for the basic forms. Both the acidic and basic forms of C8T are more easily incorporated into Brij 58 micelles than into Triton X-100 micelles. The influence of the structure of the polar head on the solubilization properties is demonstrated. Moreover, evidence for the localization of the solutes in the micelles is obtained from the comparison of the partition coefficients and from 1H NMR data.

Revealing successive steps of deprotonation of L- phosphoserine through 13C and 31P chemical shielding tensor fingerprints.

The effects of deprotonation on the (13)C and (31)P chemical shielding tensors of L-O-phosphoserine are revealed by using solid-state NMR spectroscopy and ab initio calculations. The characteristic changes in some principal elements of the (13)C and (31)P chemical shift tensors have been detected during successive steps of deprotonation of carboxyl, phosphate, and amide functional groups. The calculations carried out in a polarizable continuum taking into account the effects of the surroundings have shown their ability to reproduce correctly the changes of the principal values induced by deprotonation and to provide precious information, which is very difficult to obtain experimentally, about the concurrent changes in the orientation of chemical shielding tensors in the molecular frame. The experimentally observed subtle effects related to the deprotonation-induced modifications of intermolecular contacts involving hydrogen bonding as well as the influence of counterions on the (13)C and (31)P principal elements of the chemical shift tensors are also discussed.

Straightforward detection of the secondary ionisation of the phosphate group and pK determinations by high-resolution solid-state 31P NMR.

The suitability of high-resolution solid-state 31P NMR for a straightforward determination of the protonation state of phosphate groups as well as of their pK2 values extracted from solid state mono : dianionic ratios has been demonstrated.

Reinvestigation of the copper(II)-carcinine equilibrium system: "two-dimensional" EPR simulation and NMR relaxation studies for determining the formation constants and coordination modes.

The equilibria and solution structure of complexes formed between copper(II) and carcinine (beta-alanyl-histamine) at 2< or = pH< or =11.2 have been studied by EPR and NMR relaxation methods. Beside the species that have already been described in the literature from pH-potentiometric measurements, several new complexes have been identified and/or structurally characterized. The singlet on the EPR spectrum detected in equimolar solutions at pH 7, indicates the formation of an oligomerized (CuL)n(2n+) complex, with [NH2,Nim] coordination. The oligomerization is probably associated with the low stability of the ten-membered macrochelate ring, which would form in the mononuclear complex CuL2+. In presence of moderate excess of ligand the formation of four new bis-complexes (CuL2Hn(2+n), n=2,1 and 0/-1) was detected with [Nim][Nim], [NH2,Nim][Nim] and [NH2,N-,Nim][Nim] type co-ordination modes, respectively. At higher excess of ligand ([L]/[Cu2+]>10) and at pH approximately 7, the predominant species is CuL4H2(4+). The 1H and 13C relaxation measurements of carcinine solutions (0.6 M) in presence of 0 mM< or = [Cu2+](tot)< or = 5 mM at pH=6.8, allowed us to extract the carbon-to-metal distances, the electronic relaxation and tumbling correlation times, as well as the ligand exchange rate for the species CuL4H2(4+). According to these results, the metal ion is [4Nim] co-ordinated in the equatorial plane, while the neutral amino groups are unbounded. Since naturally occurring carcinine shows in vivo antioxidant property, the SOD-like activity of the copper(II)-carcinine system has also been investigated and the complex CuLH(-1) was found to be highly active.

pH and pK determinations by high-resolution solid-state 13C NMR: acid-base and tautomeric equilibria of lyophilized L-histidine.

Acid-base properties of lyophilized powders of L-histidine have been systematically investigated using parent solutions at pH varying from 1.8 to 10. For the first time, high-resolution solid-state 13C NMR was shown to allow separate observation of all three acid-base pairs in the successive deprotonations of the carboxylic end, the imidazolium cation, and the terminal ammonio group of histidine. 1H CRAMPS NMR spectra directly visualize the absence of the N3-H(pi) tautomer in neutral and anionic species. Solid-state titration shifts are enlarged by approximately 1-4 ppm with respect to those measured in solution, permitting unambiguous observation of conjugate acid-base pairs. Calculated pK's from solid-state acid-to-base ratios r are found equal to those classically measured in solution at 0 degrees C with a similar ionic strength of 0.1 mol x dm(-3). This proves that natural-abundance 13C solid-state determinations of r can be used to measure pK's in parent solutions without recourse to full titration curves and subsequent curve-fitting procedures. Such an approach also leads to noninvasive characterizations of the acidity of lyophilized powders, i.e., to the prediction of in situ pH of products obtained after rehydration and solubilization of powders. These results show the possibility of measuring the pK of nonvolatile acidic substrates dissolved in any sublimable solvent through lyophilization of the investigated solutions; this leads the way to pH and pK determinations when electrochemical or spectrophotometric measurements are impossible or ambiguous, e.g., for concentrated solutions, polyacids, or mixtures of acidic solutes, and possibly to the establishment of pK scales in nonaqueous solvents and in melts.

Stereoisomerism and Equilibrium Properties of Oxygen-Carrying Cobalt(II) Complexes of Histamine and Its Derivatives: A New Approach to an Old System.

The complex formation equilibria between pH 2 and 11.2 in Co(II)-L-O(2) ternary systems (L = histamine, glycylhistamine, and sarcosylhistamine) have been studied by pH-metric, spectrophotometric, and (1)H-NMR spectroscopic methods. In contrast to earlier findings, we detected several protonation states of oxygen-carrying complexes in the pH range 7-11.2. The active species in oxygen uptake is the CoL(2) complex already suggested in the Co(II)-histamine-O(2) system; however, in the case of pseudopeptides, both CoLH(-)(1) and CoL(2)H(-)(1) complexes can take up oxygen. The (1)H-NMR study revealed stereoisomerism of oxygenated species in the same protonation states, undergoing slow ligand exchange. In the case of the Co(2)(Hist)(4)(OH)(O(2)) complex, among the 20 possible geometrical isomers, at least six can be distinguished by their imidazole proton signals. The most abundant isomers have axial-equatorial imidazole coordination, presumably on steric grounds. The stability constants determined by pH studies for the above systems proved that {4N}-coordinated species have a greater affinity for oxygen uptake than the {3N}-coordinated ones. They also showed the stabilizing effect of the deprotonated amide nitrogen in the oxygenated complexes of pseudopeptides.