A simple helical macrocyclic polyazapyridinophane as a stereoselective receptor of biologically important dicarboxylates under physiological conditions

The interaction of a synthetic enantiopure azamacrocyclic receptor (L) with biologically important chiral dicarboxylates (A, 1-7) has been studied by means of potentiometric titrations in 0.15 M NaCl aqueous solution in a wide pH range. This macrocycle forms strong complexes of the type [HnLA](n-2) (with n = 0-5). As a general trend, the binding is much tighter at basic or neutral pH than in acidic medium. Interestingly, nonprotected excitatory amino acids (Asp and Glu) are strongly bound even at acidic pH. Regarding selectivity, the receptor showed stereoselective binding toward those substrates bearing an H-bonding donor at Calpha, being S-selective in most of the cases, except for glutamic acid. Thus, L displayed an excellent enantioselectivity for (S)-malate dianion (KS/KR = 11.50 at pH 10.0 and KS/KR = 6.86 at pH 7.0) and exhibited moderate enantiopreference for (S,S)-tartrate (KSS/KRR = 3.01 at pH 10 and KSS/KRR = 1.70 at pH 7.0). For this last anion, a very good diastereopreference was also observed (KSS/KRS = 8.46 at pH 10 and KSS/KRS = 4.99 at pH 7.0). On the contrary, L is smoothly R-selective toward (R)-Glu (KR/KS = 3.22 at pH 10 and KR/KS = 2.05 at pH 7.0) due to its longer and more flexible molecular structure. The stereoselectivity of the corresponding complexes decreased when decreasing pH values. For the hydroxy derivatives, mass spectrometry also reflected the trends observed by potentiometry and confirmed the receptor:dicarboxylate 1:1 stoichiometry of the supramolecular complexes. Additional experimental techniques were used to study the most stereoselective example. Solution studies by NMR suggested a good geometrical complementarity between the malate dianion and the receptor, which showed a predominant helical conformation in solution. Besides, self-diffusion rates (PGSE) of the diastereomeric complexes with malate also agree with binding data. Circular dichroism was also used in this case at different pH values, showing a very good correlation between the helical content of the receptor and the stereoselectivity of the molecular recognition process.     

Sequential one-pot glycosidations catalytically promoted: unprecedented strategy in oligosaccharide synthesis for the straightforward assemblage of the antitumor PI-88 pentasaccharide

The pentasaccharide sequence of the most active components of the antitumor drug PI-88, currently in phase II clinical trial, has been rapidly assembled in high overall yield and in only three steps starting from three monosaccharide building blocks. The procedure takes advantage of the first reported strategy of sequential one-pot glycosidations conducted exclusively under catalytic activation. In addition, the procedure relies only on shelf-stable and mild promoters such as Yb(OTf)(3) and Bi(OTf)(3).     

Glycolipids from sponges. 20. J-Coupling analysis for stereochemical assignments in furanosides: structure elucidation of vesparioside B, a glycosphingolipid from the marine sponge Spheciospongia vesparia

Reinvestigation of the glycosphingolipid composition of the marine sponge Spheciospongia vesparia revealed the presence of vesparioside B ( 2a), a new furanose-rich hexaglycosylated glycosphingolipid that is the most complex glycosphingolipid isolated from a marine sponge to date. The structure of the new compound was elucidated using extensive 2D NMR studies and chemical degradation. Particularly useful for structure elucidation of vesparioside B was a quantum mechanical computational study, showing that in furanosides a vicinal coupling constant <2.0 Hz (for H-1/H-2 or H-3/H-4) or <3.5 Hz (for H-2/H-3) is a proof of the trans orientation of the relevant protons. This general rule, combined with ROE data, allowed us to elucidate the relative stereochemistry (including anomeric configuration) of the three furanose five-membered rings.     

Complexes of Al(III) with d-gluconic acid

The complexation of Al(III) with d-gluconic acid was studied in solution by means of pH-potentiometry, ESI mass spectrometry and one- and two-dimensional NMR spectroscopy. Six complexes were found to form in solution from pH 2 to 10: [AlL]²⁺, [AlLH₋₁]⁺, [AlLH₋₂], [AlLH₋₃]⁻, [AlL₂H₋₁] and [AlL₂H₋₂]⁻. NMR spectroscopy indicated very complicated chemical exchange processes between the free ligand and gluconic acid molecules bound in the metal complexes, with different coordination modes resulting in changes both of the chemical shift and of the line shape of the signals. A solid complex [AlL₂H₋₁] · 2H₂O was isolated as a microcrystalline powder and characterized. The structures of the complexes are discussed on the basis of the spectroscopic results and MM force field calculations.     

1H-1H scalar coupling across two stacked aromatic rings: DFT calculations and experimental proof

1H-1H scalar coupling across two stacked (parallel and eclipsed) aromatic rings has been revealed through the 1D and 2D 1H NMR analysis of a [2,2]paracyclophane and rationalized by means of density functional theory (DFT) calculation of the J values.     

Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization reaction

The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anions.     

Benign‐by‐Design Solventless Mechanochemical Synthesis of Three‐, Two‐, and One‐Dimensional Hybrid Perovskites

Organic–inorganic hybrid perovskites have attracted significant attention owing to their extraordinary optoelectronic properties with applications in the fields of solar energy, lighting, photodetectors, and lasers. The rational design of these hybrid materials is a key factor in the optimization of their performance in perovskite‐based devices. Herein, a mechanochemical approach is proposed as a highly efficient, simple, and reproducible method for the preparation of four types of hybrid perovskites, which were obtained in large amounts as polycrystalline powders with high purity and excellent optoelectronics properties. Two archetypal three‐dimensional (3D) perovskites (MAPbI₃ and FAPbI₃) were synthesized, together with a bidimensional (2D) perovskite (Gua₂PbI₄) and a “double‐chain” one‐dimensional (1D) perovskite (GuaPbI₃), whose structure was elucidated by X‐ray diffraction.     

One-dimensional metal-organic framework with unprecedented heptanuclear copper units

The reaction of copper(II) sulfate, copper(II) chloride, 3,5-diacetylamino-1,2,4-triazole, and 3-acetylamino-5-amino-1,2,4-triazole in water yields green, plate-shaped crystals of [[{Cu3(mu3-OH(1/2))L(H2O)2Cl}2{mu-Cu(H2O)2Cl2}].12H2O]n (1), where L is a new triazole-derived macrocyclic ligand. The structure of 1 consists of heptanuclear (H)OCuII(3)-CuII-CuII(3)O(H) entities linked in pairs through symmetric mu3-O...H...O-mu3 hydrogen bonds to form a double-stranded one-dimensional network. A significant overall antiferromagnetic behavior has been observed for 1.     

A dinuclear copper(II) complex with adeninate bridge ligands and prominent DNA cleavage activity. Structural and spectroscopic characterization and magnetic properties

A new dinuclear copper(II) complex has been synthesized and structurally characterized: [Cu(mu-ade)(tolSO3)(phen)]2.2H2O (Hade = adenine, tolSO3- = toluenesulfonate anion). Its magnetic properties and electronic paramagnetic resonance (EPR) spectra have been studied in detail. The compound has two metal centers bridged by two adeninate NCN groups. The coordination geometry of the copper(II) ions in the dinuclear entity is distorted square pyramidal, with the four equatorial positions occupied by two phenanthroline N atoms and two N atoms from different adenine molecules. The axial position is occupied by one sulfonate O atom. Magnetic susceptibility data show antiferromagnetic behavior with an estimated exchange constant of -2J = 65 cm-1. The EPR spectrum has been obtained at both X- and Q-band frequencies; a study at different temperatures has been carried out at the latter. Above 20 K, the Q-band spectra are characteristic of S = 1 species with a small zero-field splitting parameter (D = 0.0970 cm-1). A detailed study of the DNA-complex interaction has been performed. The title complex efficiently cleaves the pUC18 plasmid in the presence of reducing agents. Both the kinetics and the mechanism of the cleavage reaction are examined and described herein.     

Synthesis and stereoselective DNA binding abilities of new optically active open-chain polyamines

The efficient synthesis of new open-chain enantiopure polyamines bearing (R,R)- and/or (S,S)-trans-cyclohexane-1,2-diamine moieties is described. The key step for the synthetic procedure is the selective monoalkylation of the cyclohexanebis(sulfonamide) core, which allows the subsequent functionalization of this moiety. Compounds bearing different combinations of absolute configurations, length of the aliphatic spacers and terminal groups have been prepared. As a demonstration of the potential utility of the obtained compounds, the preliminary DNA binding abilities of some of them have been studied by UV-measurements of melting temperatures (Tm). The effects of the absolute configuration of the corresponding chiral centers and the length of the spacer separating the cyclohexanediamine moieties on the strength of the interaction with DNA are also discussed.