Logarithmic diagrams and gran-curves as an aid in potentiometric titrations in complexometry

A detailed exposition is given of the use of logarithmic diagrams and Gran plots to construct titration curves and to determine accurately the equivalence point in potentiometric complexometric titrations.     

Tetrakis- and tris(1-Methyluracil) complexes of Pt(II): formation and properties of a carbon-bonded nucleobase species as well as of heternonuclear derivatives

The reaction of K2PtCl4 with an excess of 1-methyluracilate (1-MeU) in water at 60 degrees C leads to the formation of two major products, K2[Pt(1-MeU-N3)4].10H2O (1) and trans-K[Pt(1-MeU-N3)2(1-MeU-C5)(H2O)].3H2O (2). Addition of CuCl2 to an aqueous solution of 2 yields the mixed-metal complex trans-[PtCl(1-MeU-N3,O4)2(1-MeU-C5,O4)Cu(H2O)].H2O (4). Single-crystal X-ray analysis was carried out for 1 and 4. In both compounds, the heterometals (K+ in 1 and Cu2+ in 4) are bonded to exocyclic oxygens atoms of the 1-MeU ligands, giving rise to intermetallic distances of 3.386(2) and 3.528(2) A in 1 and 2.458(1) A in 4. The shortness of the Pt-Cu separation in 4 is consistent with a dative bond between PtII and CuII. The aqua ligand in 2 is readily substituted by a series of other ligands (e.g., 1-MeC, 9-MeGH, and CN-), as demonstrated by 1H NMR spectroscopy, with 3J(195Pt-1H(6)) coupling constants being sensitive indicators. Acid-base equilibria of 1 and 2 have been studied in detail and reveal some unexpected features: 1 has a relatively high basicity, with protonation starting below pH 5, and first and second pKa values being ca. 3.4 and 0.4, respectively. These pKa values are markedly higher than those of related neutral 2:1 or cationic 1:1 complexes and are attributed to both charge effects (-2 charge of 1) and a favorable stabilization of oxygen-protonated species by the arrangement of four exocyclic oxygen groups of 1-MeU ligands at either sides of the platinum coordination planes. Whereas in 2, H+ affinities of the three uracil ligands are in the normal range, there is a surprisingly low acidity of N(3)H of the C5-bonded uracil with a pKa of approximately 12.2, which compares with 9.75 for free 1-methyluracil. This implies that the C5-bonded PtII does not induce the typical acidifying effect of a PtII metal entity when bonded to a ring nitrogen atom of a neutral nucleobase. Rather, the effect is qualitatively similar to that of a metal ion bonded to N3 of an anionic 1-MeU ligand, which likewise increases its overall basicity as compared to neutral 1-MeUH.     

Substituted 1,8-naphthyridin-2(1H)-ones are superior to thymine in the recognition of adenine in duplex as well as triplex structures

The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degrees C (in separate positions) to 3.5 degrees C (in adjacent positions) in PNA-DNA duplexes and from 1.2 degrees C (in separate positions) to 3.2 degrees C (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degrees C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.     

Inclusion complexes of 2-phenoxyethanol and alkoxyethanols in cyclodextrins: an 1H NMR study

The association in aqueous solutions of small amphiphilic molecules [2-phenoxyethanol, PhE₁, and some α-n-alkyl-ω-hydroxyoligo(oxiethylenes], C₄E₁, C₄E₂ and C₆E₂) with β-cyclodextrin (βCD), heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) was investigated by ¹H NMR spectroscopy. The upfield shifts observed for the H3 and H5 NMR signals due to anisotropic shielding confirm that the host–guest associations are of inclusion type. The stoichiometries and the apparent inclusion constants, K _app, were determined by ¹H NMR spectroscopy using the H5 and H3 signals. The relative differences in the K _app values for βCD inclusion complexes seem to reflect the hydrophobic/hydrophilic balance of the guests. The K _app values for the PhE₁ inclusion complexes can be related to the degree of methylation and hydrophobicity variation within the considered hosts. In addition, a comparative study between βCD and TRIMEB inclusion complexes using 2D ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) NMR spectra provides structural features for these complexes which are inaccessible by other experimental methods.     

Stability and structure of mixed-ligand metal ion complexes that contain Ni2+, Cu2+, or Zn2+, and Histamine, as well as adenosine 5'-triphosphate (ATP4-) or uridine 5'-triphosphate (UTP(4-): an intricate network of equilibria

With a view on protein–nucleic acid interactions in the presence of metal ions we studied the “simple” mixed‐ligand model systems containing histamine (Ha), the metal ions Ni²⁺, Cu²⁺, or Zn²⁺ (M²⁺), and the nucleotides adenosine 5′‐triphosphate (ATP^4?) or uridine 5′‐triphosphate (UTP^4?), which will both be referred to as nucleoside 5′‐triphosphate (NTP^4?) . The stability constants of the ternary M(NTP)(Ha)^2? complexes were determined in aqueous solution by potentiometric pH titrations. We show for both ternary‐complex types, M(ATP)(Ha)^2? and M(UTP)(Ha)^2?, that intramolecular stacking between the nucleobase and the imidazole residue occurs and that the stacking intensity is approximately the same for a given M²⁺ in both types of complexes: The formation degree of the intramolecular stacks is estimated to be 20 to 50 %. Consequently, in protein–nucleic acid interactions imidazole–nucleobase stacks may well be of relevance. Furthermore, the well‐known formation of macrochelates in binary M²⁺ complexes of purine nucleotides, that is, the phosphate‐coordinated M²⁺ interacts with N7, is confirmed for the M(ATP)^2? complexes. It is concluded that upon formation of the mixed‐ligand complexes the M²⁺? N7 bond is broken and the energy needed for this process corresponds to the stability differences determined for the M(UTP)(Ha)^2? and M(ATP)(Ha)^2? complexes. It is, therefore, possible to calculate from these stability differences of the ternary complexes the formation degrees of the binary macrochelates: The closed forms amount to (65±10) %, (75±8) %, and (31±14) % for Ni(ATP)^2?, Cu(ATP)^2?, and Zn(ATP)^2?, respectively, and these percentages agree excellently with previous results obtained by different methods, confirming thus the internal validity of the data and the arguments used in the evaluation processes. Based on the overall results it is suggested that M(ATP)^2? species, when bound to an enzyme, may exist in a closed macrochelated form only, if no enzyme groups coordinate directly to the metal ion.     

Metal-free and PdII-promoted [2+3] cycloadditions of a cyclic nitrone to phthalonitriles: syntheses of oxadiazolines as well as phthalamide-PdII and dihydropyrrolyl-iminoisoindolinone-PdII complexes with high catalytic activity in Suzuki-Miyaura cross-coupling reactions

The previously unknown reactions between phthalonitriles, 1,2-(CN)2(C6)R1R2R3R4 1 (1 a, R1=R2=R3=R4=H; 1 b, R1=R2=R4=H, R3=CH3; 1 c, R1=R4=H, R2=R3=Cl; 1 d, R1=R2=R3=R4=Cl; 1 e, R1=R2=R3=R4=F), and a cyclic nitrone, -O+N==CHCH2CH2CMe2 2, proceed under heating in a sealed tube to give phthalimides 3, 2-oxadiazolyl-benzonitriles 4 or ortho-bis(oxadiazolyl)tetrafluorobenzene 4 e'. In the presence of palladium(II) chloride, phthalonitriles 1 react with 2 at room temperature, to give bis(pyrrolidin-2-ylidene)phthalamide PdII complexes 5 via metal-promoted rupture of the N--O bond of the oxadiazoline ring. The ketoimine ligands thus generated can be liberated from the metal by displacement with a diphosphine. Although the first [2+3] cycloaddition of 2 to 1 can occur in the absence of the metal to give the mono-cycloadducts 4, the second [2+3] coupling at the still-unreacted cyano group requires its activation by coordination to PdII, affording complexes 6 containing two ligated oxadiazolyl-benzonitriles. These ligands undergo either i) further cycloaddition with 2 to afford ultimately (upon rearrangement) the bis(pyrrolidinylidene)phthalamide complexes 5 or ii) N--O bond cleavage in the oxadiazoline ring with intramolecular attack of the imine nitrogen on the cyano carbon and bridging to a second PdII center to afford dimeric palladium(II) complexes 7, with chloride bridges, that bear a dihydropyrrolyl-iminoisoindolinone, a new type of ligand.The compounds were characterized by IR, 1H, and 13C NMR spectroscopy, ESI MS or FAB+ MS, elemental analyses and, in the case of 4 c, 5 a, 5 c, and 7 c, also by X-ray diffraction analysis. Complexes 5 a and 7 c show high catalytic activity for the Suzuki-Miyaura cross-coupling reaction of bromobenzene and phenylboronic acid and give biphenyl in high yields with turnover frequencies (TOFs) of up to 9.0x10(5) h(-1).     

Large mixed complexes involving uracil,cytosine, thymine and/or 1‐methyl uracil around Ca2+ ions: an electrospray ionization/MS study

We investigated the possible formation of mixed B_nB′_n′Ca²⁺ complexes where B and B′ are two different nucleobases. Electrospray ionization (ESI) mass spectrometric experiments from solutions containing two different kinds of nucleobases and calcium ions were carried out to investigate the formation of magic number clusters that may be relevant in a biological point of view. The results presented here clearly show that mixed complexes can be formed and are stable in the gas phase. This represents an important step toward more complex solutions in which several nucleobases are present simultaneously and may compete in the formation of cationized clusters. We believe that thorough investigations on such systems may help understanding biological processes that may effect the tridimensional structure of the DNA macromolecule. The formation of mixed hexamers, decamers, dodecamers and tetradecamers are clearly favored from solution containing uracil (Ura), thymine (Thy) and Ca²⁺, whereas mixed octamers are preferred from 1‐methyl uracil (MeU), uracil and Ca²⁺ mixtures. Cytosine (Cyto) can form mixed complexes with either uracil or 1‐methyl uracil or thymine. On the other hand, the main species formed in these latter cases are mixed tetramers. Copyright © 2013 John Wiley & Sons, Ltd.     

1H NMR titrations of hydroxy protons in aqueous solution as a method of investigation of intramolecular hydrogen-bonding in phosphorylated compounds: examples of myo-inositol 2-phosphate and myo-inositol 1,2,6-tris(phosphates)

1H NMR hydroxy proton titration experiments for myo-inositol 2-phosphate and myo-inositol 1,2,6-tris(phosphates) in aqueous solution are presented to demonstrate that by following OH signals versus pH, evidence can be brought for HB interaction between the hydroxyl and phosphate groups. The chemical shifts of the OH protons vicinal to phosphate groups appear deshielded by ca. 2.5 ppm with regard to those two centers removed from the phosphates. Remarkably, the deshielded protons are only present when their neighboring phosphate groups are fully deprotonated but persist until high pHs. From these results, C-OH...2-O3P-O type I, C-HO...-HO3P-O type II and C-OH...-HO3P-O type III hydrogen bonds are evidenced and discussed.     

Re(CO)(3) complexes synthesized via an improved preparation of aqueous fac-[Re(CO)(3)(H(2)O)(3)](+) as an aid in assessing (99m)Tc imaging agents. Structural characterization and solution behavior of complexes with thioether-bearing amino acids as tridentate ligands

Parallel studies of the preparation of Re and (99m)Tc agents aid in interpreting the nature of tracer (99m)Tc radiopharmaceuticals. Aqueous solutions of the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) cation are gaining wide use and are readily prepared, but such solutions of the fac-[Re(CO)(3)(H(2)O)(3)](+) cation (1) are not so easily accessible. Herein we describe a new, reliable, and straightforward preparation of aqueous solutions of 1, characterized by HPLC and ESI-MS. Treatment of solutions of 1 with thioether-bearing amino acids, AAH = S-methyl-l-cysteine (MECYSH), S-propyl-l-cysteine (PRCYSH), and methionine (METH), gave high yields of fac-Re(CO)(3)AA complexes. X-ray crystallographic and NMR analyses indicated that MECYS(-), PRCYS(-), and MET(-) were bound in fac-Re(CO)(3)AA complexes as tridentate monoanionic ligands through amino, thioether, and alpha-carboxyl groups. In CD(3)OD, (1)H NMR spectra have broad signals but have two sets of signals at -10 degrees C, consistent with two isomers with different configurations at the pyramidal sulfur; these interconvert slowly on the NMR time scale at low temperatures. Indeed, the crystal structure of the fac-Re(CO)(3)(PRCYS) reveals a mixture of the two possible diastereoisomers. S-(Carboxymethyl)-l-cysteine (CCMH(2)) and 1 gave two products, 5A (kinetically favored) and 5B (thermodynamically favored). X-ray crystallographic analyses of a crystal of 5B and of a 1:1 cocrystal of 5A and 5B showed that 5A and 5B are diastereoisomers with the CCMH(-) alpha-carboxyl group dangling. In addition to the amino and thioether groups, the S-(carboxymethyl) carboxyl group is coordinated, a feature that slows interconversion of diastereoisomers relative to the other fac-Re(CO)(3)AA complexes because interconversion can now occur only after the rupture of Re-ligand bonds. These N, O, and S tridentate adducts are quite stable, and the grouping has promise in (99m)Tc(CO)(3) tracer development.     

Stereoselective synthesis of highly enantioenriched 3-methyl-2-cyclohexen-1-ones possessing an asymmetric quaternary carbon as C-4 or C-6: a sugar template approach

The 1,4-addition of the enolate generated from α-methylated acetoacetate incorporated at C-4 of methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-d-glucopyranoside to methyl vinyl ketone, followed by aldol condensation of the resulting 1,4-addition product under two base-mediated conditions, provided 4-O-functionalized d-glucose derivatives with high diastereoselectivity. These products install a 3-methyl-2-cyclohexen-1-one-4- (or -6-) carboxylic acid as the O-4 ester, in which C-4 or C-6 is an asymmetric quaternary carbon. Removal of the sugar template from those aldol condensation products provided synthetically useful 3,6-dimethyl-2-cyclohexen-1-one-6-carboxylic acid and 3,4-dimethyl-2-cyclohexen-1-one-4-carboxylic acid derivatives both in high enantioenriched forms.     

1-(2-Hydroxyethyl)-5-mercapto-1H-tetrazole as ligand in Cu(I) complexes with or without X-ions (X = Cl,Br, I): synthesis,crystal structures and properties

Four Cu(I) complexes with 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (Hhmt) as a ligand, [Cu(hmt)]_n (1), [Cu₂Cl(hmt)]_n (2), [Cu₄Br(hmt)₃]_n (3), and [Cu₄I(hmt)₃]_n (4), have been synthesized. In 1–4, hmt adopts a μ₄-η^1?:^? η^1?:^? ηS² coordinate mode to join the adjacent Cu(I) ions, which form different two-dimensional (2-D) structures. In 1, the neighboring four Cu(I) atoms are connected by μ₄-hmt to form a 2-D structure. In 2, the Cu(I) ions are firstly connected with Cl ions to form a 1-D [Cu₄Cl₂] subunit chain, which then have been bridged by hmt to form a 2-D structure. However, the inorganic [Cu₄Br] and [Cu₄I] motifs are respectively connected by hmt to form 2-D structures in isostructural 3 and 4. In addition, the fluorescent properties and the thermal stability properties of 1–4 have been investigated.     

Resonance enhanced tunneling in an asymmetric double well potential: The 2B1Σ+ state of HCl

We investigate the exact quantum tunneling dynamics using a density matrix approach in the 2B¹Σ⁺ state of HCl which has recently been calculated to be an asymmetric double well potential. With the exact dynamics and a simple model of the collisional interaction process the transfer rate shows strong resonance enhancement for particular rotational states. The transmission coefficient approach, commonly used in tunneling calculations, shows no such features. This system suggests the possibility of the experimental observation of such rotationally induced tunneling resonances (perhaps in HCl in the gas phase). Although not strongly coupled to the environment itself the large resonance effects, caused by near degeneracies, in this system suggest that in treating systems which are strongly coupled to their environment (such as in the solid state) the exact quantum dynamics should be used rather than the transmission coefficient model.     

Different rotamer states of cytosine nucleobases in heteronuclear PtPd-, PtPd2, and Pt2Pd2Ag complexes derived from [Pt(2,2'-bpy)(1-MeC-N3)2]2+ (1-MeC = 1-methylcytosine): first examples of species with head-head oriented 1-MeC(-) ligands

[Pt(2,2'-bpy)(1-MeC-N3)(2)](NO(3))(2) (1) (2,2'-bpy = 2,2'-bipyridine; 1-MeC = 1-methylcytosine) exists in water in an equilibrium of head-tail and head-head rotamers, with the former exceeding the latter by a factor of ca. 20 at room temperature. Nevertheless, 1 reacts with (en)Pd(II) (en = ethylenediamine) to give preferentially the dinuclear complex [Pt(2,2'-bpy)(1-MeC(-)-N3,N4)(2)Pd(en)](NO(3))(2)·5H(2)O (2) with head-head arranged 1-methylctosinato (1-MeC(-)) ligands and Pd being coordinated to two exocyclic N4H(-) positions. Addition of AgNO(3) to a solution of 2 leads to formation of a pentanuclear chain compound [{Pt(2,2'-bpy)(1-MeC(-))(2)Pd(en)}(2)Ag](NO(3))(5)·14H(2)O (5) in which Ag(+) cross-links two cations of 2 via the four available O2 sites of the 1-MeC(-) ligands. 2 and 5 appear to be the first X-ray structurally characterized examples of di- and multinuclear complexes derived from a Pt(II) species with two cis-positioned cytosinato ligands adopting a head-head arrangement. (tmeda)Pd(II) (tmeda = N,N,N',N'-tetramethylethylenediamine) and (2,2'-bpy)Pd(II) behave differently toward 1 in that in their derivatives the head-tail orientation of the 1-MeC(-) nucleobases is retained. In [Pt(2,2'-bpy)(1-MeC(-))(2){Pd(2,2'-bpy)}(2)](NO(3))(4)·10H(2)O (4), both (2,2'-bpy)Pd(II) entities are pairwise bonded to N4H(-) and O2 sites of the two 1-MeC(-) rings, whereas in [Pt(2,2'-bpy)(1-MeC(-))(2){Pd(tmeda)}(2)(NO(3))](NO(3))(3)·5H(2)O (3) only one of the two (tmeda)Pd(II) units is chelated to N4H(-) and O2. The second (tmeda)Pd(II) is monofunctionally attached to a single N4H(-) site. On the basis of these established binding patterns, ways to the formation of mixed Pt/Pd complexes and possible intermediates are proposed. The methylene protons of the en ligand in 2 are special in that they display two multiplets separated by 0.64 ppm in the (1)H NMR spectrum.     

Beta-turn mimic in tripeptide with Phe(1)-Aib(2) as corner residues and beta-strand structure in an isomeric tripeptide: an X-ray diffraction study

A single crystal X-ray diffraction study of the tripeptide Boc-Phe-Aib-Leu-OMe (Aib = alpha-aminoisobutyric acid) reveals that it forms structurally one of the best type II beta-turns so far reported in tripeptides, stabilized by 10 atom intramolecular hydrogen bonding. In contrast, the isomeric tripeptide Boc-Phe-Leu-Aib-OMe adopts a beta-strand like conformation. Interestingly, a previously reported structure of another isomeric tripeptide, Boc-Leu-Aib-Phe-OMe, shows a double bend conformation without any intramolecular hydrogen bonding. These results demonstrate an example of the creation of structural diversities in the backbone of small peptides depending upon the co-operative steric interactions amongst the amino acid residues.     

New 1:1 and 2:1 salts in the `dl‐norvaline–maleic acid' system as an example of assembling various crystal structures from similar supramolecular building blocks

Molecular salts and cocrystals of amino acids have potential applications as molecular materials with nonlinear optical, ferroelectric, piezoelectric, and other various target physical properties. The wide choice of amino acids and coformers makes it possible to design various crystal structures. The amino acid–maleic acid system provides a perfect example of a rich variety of crystal structures with different stoichiometries, symmetries and packing motifs built from the molecular building blocks, which are either exactly the same, or differ merely by protonation or as optical isomers. The present paper reports the crystal structures of two new salts of the dl ‐norvaline–maleic acid system with 1:1 and 2:1 stoichiometries, namely dl ‐norvalinium hydrogen maleate, C₅H₁₂NO₂⁺·C₄H₃O₄⁻, (I), and dl ‐norvalinium hydrogen maleate–dl ‐norvaline, C₅H₁₂NO₂⁺·C₄H₃O₄⁻·C₅H₁₁NO₂, (II). These are the first examples of molecular salts of dl ‐norvaline with an organic anion. The crystal structure of (I) has the same C ₂²(12) structure‐forming motif which is common for hydrogen maleates of amino acids. The structure of (II) has dimeric cations. Of special interest is that the single crystals of (I) which are originally formed on crystallization from aqueous solution transform into single crystals of (II) if stored in the mother liquor for several hours.     

Co-solvent effects for preventing broadening or loss of early eluted peaks when using concurrent solvent evaporation in capillary GC. Part 2: n-Heptane in n-pentane as an example

Co-solvent effects are applied to allow use of concurrent solvent evaporation for applications requiring analysis of compounds eluted less than some 50° above the column temperature during sample introduction, i.e. at oven temperatures below some 100–120°C. Required conditions such as GC even temperature, concentration of the co-solvent and length of the uncoated pre-column (retention gap) are studied theoretically as well as experimentally for the case of n-heptane as co-solvent in n-pentane.