Aza-crown macrocycles as chiral solvating agents for mandelic acid derivatives.

A series of new chiral macrocycles containing the trans-1,2-diaminocyclohexane (DACH) subunit and arene- and oligoethylene glycol-derived spacers has been prepared in enantiomerically pure form. Four of the macrocycles have been characterized by X-ray crystallography, which reveals a consistent mode of intramolecular N-H···N hydrogen bonding and conformational variations about the N-benzylic bonds. Most of the macrocycles were found to differentiate the enantiomers of mandelic acid (MA) by (1)H NMR spectroscopy in CDCl(3); within the series of macrocycles tested, enantiodiscrimination was promoted by (i) a meta-linkage geometry about the arene spacer, (ii) the presence of naphthalene- rather than phenylene-derived arene spacers, and (iii) increasing length of the oligoethylene glycol bridge. (1)H NMR titrations were performed with optically pure MA samples, and the data were fitted to a simultaneous 1:1 and 2:1 binding model, yielding estimates of 2:1 binding constants between some of the macrocycles and MA enantiomers. In several cases, NOESY spectra of the MA:macrocycle complexes show differential intramolecular correlations between protons adjacent to the amine and carboxylic acid groups of the macrocycles and MA enantiomers, respectively, thus demonstrating geometric differences between the diastereomeric intermolecular complexes. The three most effective macrocycles were employed as chiral solvating agents (CSAs) to determine the enantiomeric excess (ee) of 18 MA samples over a wide ee range and with very high accuracy (1% absolute error).

Thermoresponsive dynamers: thermally induced, reversible chain elongation of amphiphilic poly(acylhydrazones).

A nanostructured poly(acylhydrazone), which is reversibly formed in acidic aqueous solution from di(aldehyde) and di(acylhydrazine) monomers with appended hexaglyme groups, was found to display lower critical solution (LCS) behavior. Remarkably, under acidic conditions in which polymerization is reversible, large and reversible molecular weight (M(w)) increases were observed in response to elevated temperatures, both below and above the LCS temperature. No variation in M(w) was evident under neutral and alkaline conditions, in which the acylhydrazone condensation is essentially irreversible. Results of turbidometry studies, size-exclusion chromatography-multiangle laser light scattering (SEC-MALLS), and transmission electron microscopy (TEM) suggest that heating the polymer below the LCS temperature leads to polymer growth with preservation of the characteristic nanostructured morphology, whereas the onset of the microphase separated state causes a fundamental change in morphology, in which the polymer chains aggregate into larger bundles and fibers. van't Hoff analysis of a small molecule model system indicates that the acylhydrazone condensation is enthalpy driven (ΔH(eq) = -8.2 ± 0.2 kcal·mol(-1) and ΔS(eq) = -11.1 ± 0.4 = cal·mol(-1)·K(-1)), which suggests that the observed polymer growth with temperature is not a consequence of the intrinsic thermodynamics of the intermonomer linkage but is likely the result of the thermoresponsive characteristics conferred by the multiple hexaglyme groups. The system described displays double control of the dynamer state by two orthogonal agents, heat and protons (pH). It also represents a prototype for dynamic materials displaying multiple control adaptive behavior.

Using enantioselective indicator displacement assays to determine the enantiomeric excess of alpha-amino acids.

Enantioselective indicator displacement assays (eIDAs) were used for the determination of enantiomeric excess (ee) of alpha-amino acids as an alternative to the labor-intensive technique of chromatography. In this study, eIDAs were implemented by the use of two chiral receptors [(Cu(II)(1)](2+), [Cu(II)(2)](2+)) in conjunction with the indicator chrome azurol S. The two receptors were able to enantioselectively discriminate 13 of the 17 analyzed alpha-amino acids. Enantiomeric excess calibration curves were made using both receptors and then used to analyze true test samples to check the system's ability to determine ee accurately. The proposed method uses a conventional UV-vis spectrophotometer to monitor the colorimetric signal, which allows for a potential high-throughput screening (HTS) method for determining ee. The techniques created consistently produced results accurate enough for rapid preliminary determination of ee.

Pattern-based discrimination of enantiomeric and structurally similar amino acids: an optical mimic of the mammalian taste response.

This manuscript describes an optical enantioselective pattern-based sensing array. A differential array of enantioselective indicator displacement assays was constructed and used to demonstrate simultaneous discrimination of enantiomeric and structurally similar alpha-amino acids. Interpretation of the output patterns by principle component analysis leads to the separation of enantio- and chemoselective information along orthogonal variance axes when chiral receptors of opposite enantiomeric preference are included. A general principle is delineated that correlates array design with the achievement of enantiomeric discrimination analogous to the mammalian gustation response to the amino acids.

"Naked-eye" detection of histidine by regulation of Cu(II) coordination modes.

The association of various alpha-amino acids with four new, coordinatively unsaturated metal complexes ([Cu(5)]2+, [Cu(6)]2+, [Cu(7)]2+, and [Zn(8)]2+) was examined. The receptors [Cu(5)]2+ and [Cu(7)]2+ were found to discriminate histidine (His) from other zwitterionic alpha-amino acids by means of indicator-displacement assays (IDAs) using 5(6)-carboxyfluorescein as an indicator in buffered methanol/water (3:1) solvent. The colorimetric detection of His was achieved by using this IDA method, which appears to owe its selectivity to a unique process involving disruption of the host complex to form a 2:1 His/Cu(II) complex rather than simple indicator displacement. The occurrence of distinct intermolecular coordination processes in response to the introduction of a different amino acid is observed. X-ray crystal structures of the host metal complexes were obtained and exhibit the adoption of a variety of coordination geometries about the metal center.

Colorimetric enantiodiscrimination of alpha-amino acids in protic media.

A new method is described for the determination of optical purity of alpha-amino acid samples in protic media. No derivatization of the analyte or multistep synthesis is required, and high accuracy is obtained from the colorimetric output. Chiral discrimination is achieved through the use of an optically pure trans-1,2-diaminocyclohexane-derived Cu(II)-containing host that differentiates amino acid enantiomers by a factor of about 2. Enantioselective signaling arises from the implementation of an indicator displacement assay based on competitive Cu(II) coordination involving the chiral Cu(II)-containing host, the amino acid guest, and a metal ion indicator. The molecular structure of the host/guest complex was determined by X-ray analysis and exhibits chelation of the Cu(II) center by the amino acid to provide substrate organization.

2,6-di(pyrimidin-4-yl)pyridine ligands with nitrogen-containing auxiliaries: the formation of functionalized molecular clefts upon metal coordination.

A series of ligands (1-4) based on a 2,6-di(pyrimidin-4-yl)pyridine scaffold have been synthesized, and their abilities to form complexes with Zn(II) and Cu(II) have been determined using UV/vis spectroscopy in buffered aqueous solution (0.01 M N-[2-hydroxyethyl]piperazine-N'-[3-ethanesulfonic acid] (HEPES) at pH = 6.8). The Zn(II) complex of 1 was determined to have a formation constant of 8.4 x 10(3) M(-)(1) while the formation constant of the Cu(II) complex was found to be 1 x 10(6) M(-)(1). The presence of auxiliary amines in 2 increased the stability of the Zn(II) complex relative to that of 1 by a factor of over 40, suggesting possible coordination of the auxiliaries to the Zn(II) center. The guanidinium and 2-amino-4,5-dihydro-imidazolinium groups of 3 and 4 considerably diminished the stability of the Zn(II) and Cu(II) complexes relative to those of 1. X-ray crystal structures of 1-Zn, 3-Zn, 4, and 4-Zn were obtained and are discussed. A significant increase in the stability of 3-Zn, but not in the stability 1-Zn, was observed upon the addition of 1 equiv of sodium phosphate, implicating a stabilizing interaction of the guanidinium groups of 3-Zn and the phosphate anion.