Chiral discrimination in the structures and energetics of association of stereoisomeric salts of mandelic acid with .alpha.-phenethylamine, ephedrine, and pseudoephedrine

Zingg, S. P.; Arnett, Edward M.; McPhail, Andrew T.; Bothner‐By, Aksel A.; Gilkerson, W. R.

doi:10.1021/ja00213a033

Cited by 98 publications

(75 citation statements)

References 4 publications

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“…Metha nol. an amphiprotic solvent, has been used to prepare ion pairs [25][26][27], Another method of preparing ion pairs was to react the lidocaine base directly with the nalkanoic acid in equimolar amounts, because n-alkanoic acids were either liquids at room temperature or had very low melting points. The decision to directly react the acid and the base was prompted by the fact that the pKa difference between the lidocaine base and the n-alkanoic acids was about two units, showing that proton exchange could take place in the absence of a solvent.…”

Section: Lidocaine-n-alkanoate Ion Pair Synthesismentioning

confidence: 99%

The Possibility of Lidocaine Ion Pair Absorption Through Excised Hairless Mouse Skin

Nash

Mehta

Matias

et al. 1992

Skin Pharmacol Physiol

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The purpose of the present research was to test the ion pair absorption hypothesis with respect to the topical route of drug delivery. The experiment consisted of preparing various lido-cainen-alkanoate ion pairs, then characterizing them by proton magnetic resonance spectroscopy, elemental analysis and conductivity. Percutaneous absorption studies through excised hairless mouse skin were carried out using ethanolic solution of radiolabeled ¹⁴C-lidocaine-octanoate, ¹⁴C-lido-caine-decanoate and ¹⁴C-lidocaine-dodecanoate. Studies were conducted under steady-state conditions using Bronaugh’s flow-through apparatus and normal saline as the receptor fluid. Ethanolic solution of a lidocaine base served as a control. The apparent differences in flux between lidocaine and the various ion pairs were statistically significant (p < 0.05). The differences among the fluxes of the various ion pairs were not statistically significant (p > 0.05), nor were the differences in lag times (p > 0.05). The difference between the flux values of lidocaine- 1-¹⁴C-dodecanoate and ¹⁴C-lidocaine-dodecanoate infers that lidocaine-dodecanoate did not cross the excised, full-thickness, hairless mouse skin as an intact 1:1 ion pair. The formation of weakly associated ion pairs was suggested by the apparent low-association constants (K_a = 15-17 liters/mol) obtained at 25 °C in methanol by conductometric analysis.

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Section: Lidocaine-n-alkanoate Ion Pair Synthesismentioning

confidence: 99%

The Possibility of Lidocaine Ion Pair Absorption Through Excised Hairless Mouse Skin

Nash

Mehta

Matias

et al. 1992

Skin Pharmacol Physiol

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“…The ICD intensity of the poly-1-(R)-2 complex corresponding to an excess of a single-handed helix of the polymer backbone was very weak compared with those of PCPA, PPPA, and PEPPA induced by (R)-2; the second Cotton intensities (Á" 2nd ) of the complexes of PCPA, PPPA, and PEPPA with (R)-2 in DMSO were À9:27, þ11:2, free acid and base, the ion pair, and the free ions as shown in Scheme 1. 27,36,[44][45][46] Among these three species, the ion pair formation is essential for the helicity induction in one-handedness excess, resulting in the appearance of an intense ICD in the polymer backbone as reported for PCPA with chiral amines. 36 The pendant sulfonic acid of poly-1 is more acidic than the carboxylic acid of the PCPA and phosphonic acid of the PPPA and PEPPA.…”

Section: Resultsmentioning

confidence: 99%

Helicity Induction on a Poly(phenylacetylene) Derivative Bearing a Sulfonic Acid Pendant with Chiral Amines and Memory of the Macromolecular Helicity in Dimethyl Sulfoxide

Hasegawa

Maeda

Ishiguro

et al. 2006

Polym J

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ABSTRACT:A stereoregular poly(phenylacetylene) derivative bearing a sulfonic acid residue (poly-1) as the pendant was found to form a predominantly one-handed helix upon complexation with various chiral amines through noncovalent acid-base interactions in dimethyl sulfoxide (DMSO). In sharp contrast to analogous poly(phenylacetylene)s bearing relatively weak carboxy and phosphonic acid residues as the pendants, the poly-1-amine complexes exhibited a weak induced circular dichroism (ICD) in the UV-visible region of the polymer backbone. However, in the presence of a strong acid, such as p-toluenesulfonic acid (TosOH), the ICD intensity significantly increased, resulting from a favorable ion pair formation between the sulfonic acid residues of the poly-1 and chiral amines, leading to an increase in the helical sense excess of poly-1. Moreover, the macromolecular helicity of poly-1 induced by chiral amines in the presence of TosOH was ''memorized'' after the chiral amines and their salts were completely removed and replaced with an achiral diamine, i.e., ethylene diamine, in DMSO, while no memory effect was observed for a helical poly-1 induced by the same chiral amines in the absence of TosOH.

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“…1 A melting point of 110.8°C and a heat of fusion of 6.7 kcal/ mol were reported for (+)-(1S2R)-ephedrinium (−)-(R)-mandelate. In the earlier stages of our preparative work, crystallization of the (+)-(1S2R)-ephedrinium (−)-(R)-mandelate from benzene yielded a mixture of two polymorphs.…”

Section: Heat Of Solution Of the (+) Ephedrinium (−) Mandelate (T M =mentioning

confidence: 99%

“…(2), ␣ is the degree of dissociation and ⌬H dissn is the enthalpy of dissociation of the ion pairs to free ions. In the study of Zingg et al, 1 the degree of dissociation was determined by conductimetry and ⌬H dissn was obtained from Eq. (3):…”

Section: Introductionmentioning

confidence: 99%

“…Primary sources of data are crystal structures of diastereomeric salt pairs and the associated enthalpy differences. Despite the importance of these data only a single study 1 has reported differential enthalpies for diastereomeric salt pairs. Presently, crystal structural and enthalpy difference data are currently available for only two diastereomeric salt pairs.…”

mentioning

confidence: 99%

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Calorimetric determination of differential integral heats of solution for a set of diastereomeric salt pairs

1997

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Chiral discrimination in the structures and energetics of association of stereoisomeric salts of mandelic acid with .alpha.-phenethylamine, ephedrine, and pseudoephedrine

Cited by 98 publications

References 4 publications

The Possibility of Lidocaine Ion Pair Absorption Through Excised Hairless Mouse Skin

The Possibility of Lidocaine Ion Pair Absorption Through Excised Hairless Mouse Skin

Helicity Induction on a Poly(phenylacetylene) Derivative Bearing a Sulfonic Acid Pendant with Chiral Amines and Memory of the Macromolecular Helicity in Dimethyl Sulfoxide

Calorimetric determination of differential integral heats of solution for a set of diastereomeric salt pairs

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