Carolina Godoy-Alcántar

Macrocyclic Diorganotin Complexes of γ-Amino Acid Dithiocarbamates as Hosts for Ion-Pair Recognition

The dimethyl-, di-n-butyl-, and diphenyltin(IV) dithiocarbamate (dtc) complexes [{R2Sn(L-dtc)}x] 1-7 (1, L = L1, R = Me; 2, L = L1, R = n-Bu; 3, L = L2, R = Me, x = infinity; 4, L = L2, R = n-Bu; 5, L = L3, R = Me, x = 2; 6, L = L3, R = n-Bu, x = 2; 7, L = L3, R = Ph, x = 2) have been prepared from a series of secondary amino acid (AA) homologues as starting materials: N-benzylglycine (alpha-AA derivative = L1), N-benzyl-3-aminopropionic acid (beta-AA derivative = L2), and N-benzyl-4-aminobutyric acid (gamma-AA derivative = L3). The resulting compounds have been characterized by elemental analysis, mass spectrometry, IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy, thermogravimetric analysis, and X-ray crystallography, showing that in all complexes both functional groups of the heteroleptic ligands are coordinated to the tin atoms. By X-ray diffraction analysis, it could be shown that [{Me2Sn(L2-dtc)}x] (3) is polymeric in the solid state, while the complexes derived from L3 (5-7) have dinuclear 18-membered macrocyclic structures of the composition [{R2Sn(L3-dtc)}2]. For the remaining compounds, it could not be established with certainty whether the structures are macrocyclic or polymeric. A theoretical investigation at the B3LYP/SBKJC(d,p) level of theory indicated that the alpha-AA-dtc complexes might have trinuclear macrocyclic structures. The macrocyclic complexes 5-7 have a double-calix-shaped conformation with two cavities large enough for the inclusion of aliphatic and aromatic guest molecules. They are self-complementary for the formation of supramolecuar synthons that give rise to 1D molecular arrangements in the solid state. Preliminary recognition experiments with tetrabutylammonium acetate have shown that the [{R2Sn(L3-dtc)}2] macrocycles 6 and 7 might interact simultaneously with anions (AcO(-)), which coordinate to the tin atoms, and organic cations (TBA(+)), which accommodate within the hydrophobic cavity (ion-pair recognition).

Fluorescent anion sensing by bisquinolinium pyridine-2,6-dicarboxamide receptors in water

Dicationic N-methylated at quinolyl moieties derivatives of three isomers of N,N′-bis(quinolyl)pyridine-2,6-dicarboxamide, and respective N-methyl quinolinium benzamides as reference compounds, have been prepared and characterized by crystal structures, spectral and acid–base properties in water. First pKa values of dicarboxamides between 8.1 and 9.3 determined spectrophotometrically are unusually low for amides. Dicarboxamide derivatives of 3- (1) and 6-aminoquinoline (2) undergo efficient fluorescence quenching by halide, acetate, pyrophosphate and nucleotide anions but the derivative of 5-aminoquinoline (3) shows very small quenching effects. The shape of Stern–Volmer plots for dicarboxamides indicates the existence of ground state complexation with anions, which is absent for related benzamides. Association constants, KA, with anions were calculated from analysis of concentration profiles of the quenching effects on the fluorescence of 1 and 2. Quenching by nucleoside triphosphates is much more efficient than by inorganic anions. Efficient binding of even simple inorganic anions by neutral amide N–H donors in water is attributed to high acidity of amides and preorganized rigid structure of the receptors.

Comparative analysis of M–O, M–S and cation–π(arene) interactions in the alkali metal (Na+, K+, Rb+, Cs+) bis-dithiocarbamate salts of N,N′-dibenzyl-1,2-ethylenediamine

The alkali metal (Na+, K+, Rb+, Cs+) bis-dithiocarbamate (bis-dtc) salts of N,N′-dibenzyl-1,2-ethylenediamine have been prepared from the reaction of N,N′-dibenzyl-1,2-ethylenediamine with carbon disulfide in the presence of two equivalents of the corresponding alkali metal hydroxide. Additionally, the analogous triethylammonium derivative has been obtained. The resulting compounds have been analyzed as far as possible by elemental analysis, FAB+ mass spectrometry, IR, UV-Vis and NMR (1H, 13C) spectroscopy, and single-crystal X-ray diffraction, showing that the composition of the metal salts can be described by the general formula [{[(H2O)xM-µ-(H2O)yM(H2O)x][bis-dtc]}n] (1, M = Na+, x = 3, y = 2; 2, M = K+, x = 1, y = 2; 3, M = Rb+, x = 0, y = 1; 4, M = Cs+, x = 0, y = 1; 5, M = Et3HN+, x = 0, y = 0). The solid-state and solution studies showed that all alkali metal ions participate in the formation of M–O and cation-π(arene) interactions, while M–S interactions are only observed for the larger alkali metals K+, Rb+ and Cs+. As expected, within the alkali metal group there is a clear tendency for a decreasing number of M–O bonds in favor of M–S and cation–π(arene) interactions, however, only K+ forms a semi-sandwich type complex with η6-coordination.

Recognition of α-amino acid derivatives by N,N′-dibenzylated S,S-(+)-tetrandrine

Complexation of free and N-acetylated α-amino acid anions (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type N,N′-dibenzylated chiral derivative of a bisisoquinoline macrocyclic alkaloid S,S-(+)-tetrandrine (DBT) has been studied by 1H-NMR titrations in D2O. In contrast to other macrocyclic hosts like cyclodextrins and calixarenes, DBT shows highest affinity and large enantioselectivity (K(S)/K(R) ≥ 10) toward smaller N-acetylalanine and binds larger phenylalanine derivatives more weakly and non-selectively. With 1,2,3,4-tetrahydroisoquinoline-3-carboxylate, a rigid analog of phenylalanine, binding again becomes enantioselective with K(S)/K(R) = 3.8. The binding specificity of DBT is rationalized on the basis of molecular mechanics calculations.

Protonation of kanamycin A: detailing of thermodynamics and protonation sites assignment.

Protonation of an aminoglycoside antibiotic kanamycin A sulfate was studied by potentiometric titrations at variable ionic strength, sulfate concentration and temperature. From these results the association constants of differently protonated forms of kanamycin A with sulfate and enthalpy changes for protonation of each amino group were determined. The protonation of all amino groups of kanamycin A is exothermic, but the protonation enthalpy does not correlate with basicity as in a case of simple polyamines. The sites of stepwise protonation of kanamycin A have been assigned by analysis of (1)H-(13)C-HSQC spectra at variable pH in D(2)O. Plots of chemical shifts for each H and C atom of kanamycin A vs. pH were fitted to the theoretical equation relating them to pK(a) values of ionogenic groups and it was observed that changes in chemical shifts of all atoms in ring C were controlled by ionization of a single amino group with pK(a) 7.98, in ring B by ionization of two amino groups with pK(a) 6.61 and 8.54, but in ring A all atoms felt ionization of one group with pK(a) 9.19 and some atoms felt ionization of a second group with pK(a) 6.51, which therefore should belong to amino group at C3 in ring B positioned closer to the ring A while higher pK(a) 8.54 can be assigned to the group at C1. This resolves the previously existed uncertainty in assignment of protonation sites in rings B and C.

Nucleotide recognition by protonated aminoglycosides

Interactions of protonated forms of kanamycin A with nucleotides and several simple phosphate anions have been studied by potentiometric and NMR titrations. The affinity of kanamycin A to anions is comparable to that observed with other aliphatic polyammonium receptors of similar charge, but it discriminates triphosphate nucleotides with different nucleobases with binding constants following the order GTP≫CTP ≈ ATP. Kanamycin A also binds the respective uncharged nucleosides with the same selectivity. Binding of ATP is exothermic with a negative entropic contribution in contrast to what is expected for simple ion pairing. Other tested aminoglycosides, amikacin and streptomycin, bind ATP less efficiently than kanamycin A. Models of structures of kanamycin A complexes with ATP and GTP obtained by molecular mechanics (OPLS-2005) calculations based on 1H and 31P NMR data confirm the possibility of nucleotide discrimination by simultaneous ion pairing of terminal nucleotide phosphate groups with ammonium sites of rings B and C and hydrogen bonding of the nucleobase at the ring A of the aminoglycoside.

Anion recognition by thiostrepton

A bicyclic polypeptide antibiotic thiostrepton forms both 1:1 and 1:2 complexes with anions (as tetrabutylammonium salts) in organic solvents with K2 >K1 for F- and K2<<K1 for all other anions studied. Relative stabilities of 1:1 complexes in DMSO are AcO- approximatelyF->>Cl-, Br-, HSO4-, H2PO4-, but in CHCl3 they follow a different order: Cl- approximatelyHSO4- >F- approximately AcO- > Br > H2PO4-. The binding mode of anions to thiostrepton is discussed on the basis of solvent effects on the complexation selectivity.

Molecular Recognition of Thymine and Uracil in Water by an Amino-, Amido-, and Carboxymethyl-functionalized Pyridinophane

A new water soluble 26-membered macrocyclic pyridinophane functionalized by amide and carboxymethyl groups has been synthesized in a single step reaction and characterized by elemental analysis, mass spectrometry (FAB+), UV-vis, fluorescence, and 1H NMR spectroscopy as well as single-crystal X-ray diffraction analysis. Its complexation properties with the nucleobases thymine and uracil have been explored in aqueous media by performing 1H NMR titration experiments and potentiometric studies. The binding constants of the 1:1 host-guest complexes were determined as 103 M− 1 by proton NMR and 102–103 M− 1 by potentiometry. Semiempirical molecular modelling studies have shown that the nucleobases are included within the cavity of the macrocyclic receptor and that the complexes are stabilized by hydrogen bonding.

Crystal structure of N,N′-bis[2-((benzyl){[5-(di­methyl­amino)naph­tha­len-1-yl]sulfonyl}amino)ethyl]naphthalene-1,8:4,5-tetracarboximide 1,2-di­chloro­benzene tris­olvate

In the structure of the title compound, cooperative C—H⋯O=C, C—H⋯π and offset π–π interactions generate supramolecular nanotubes which accommodate the 2,3-dichlorobenzene solvent molecules.

Crystal structure of 1,3-bis-(1,3-dioxoisoindolin-1-yl)urea dihydrate: a urea-based anion receptor.

The title compound possesses twofold rotation symmetry, with the planes of the phthalimide moieties inclined to one another by 73.53 (7)° and by 78.62 (9)° to that of the urea unit. In the crystal, molecules are linked via N—H⋯O and O—H⋯O hydrogen bonds, forming a three-dimensional framework structure.