Spectroscopic investigations into the acid–base properties of nicotine at different temperatures

摘要

Electroniccirculardichroism(ECD)spectrometrictitrationmethodologywasusedtodeterminetheacidionisationconstants(pKa)of(S)-(?)-nicotine.Thermostaticallycontrolledinstrumentationallowedmeasurementstobeconductedbetween20and40°CandthechangesinpKawithtemperaturewerecharacterised.Themethodologywasrobust,preciseandcouldbeutilisedforotherchiralchromogeniccompounds.Webelievethisarticleisthefirstreportoftheuseofchiropticalspectroscopytocharacterisetheacid–basepropertiesofasmallbio-activemolecule,andthetechniquecouldbecomethemethodofchoicefordefiningtheseattributesinsimilarmolecules.For(S)-(?)-nicotinethetwopKavalueswerefoundtobe2.96and8.07at20°C,2.85and7.89at25°C,2.84and7.83at30°Cand2.74and7.57at40°C.Usingthevan'tHoffrelationshipthepKaofthepyrrolidylionisationat37°Cwascalculatedas7.65.Changesintheionisationstatusofnicotinewithtemperatureareofinteresttoinvestigatorsstudyingtheattributesofnicotinederivedfromthehumanuseoforaltobaccoproducts.ThereversibilityofUVandECDspectraofnicotinewithtemperaturebetween10and87°Cwasdemonstratedforbothenantiomers.AdditionallytherewasgoodevidencethatatpH9.5nicotineunderwentconformationalchange,andthetransitionmid-pointoccurredat49.7and49.4°Cfor(S)and(R)-nicotinerespectively...