Determination of the relative pKa's of mixtures of organic acids using NMR titration experiments based on aliased 1H–13C HSQC spectra

摘要

NMRtitrationscanbeusedtosimultaneouslydeterminethepKa'sofmixturesoforganicacidsandbasesprovidedchemicalshiftsaresensitivetotheirchangeofprotonationstates.Carbonsareinprinciplebetterprobesthanprotonsbecausetheirchemicalshiftsaretypicallymoresensitivetothechangesintheelectronicdensitiesofthefunctionalgroupstheyareboundto.Theyarealsolesspronetooverlap,donotsufferfromsecond-ordereffectsandarelesssensitivetochangesinsolventconditions.RecordingHSQCspectrasatisfactorilyreducesthelackofsensitivityofcarbon-detectedexperimentsandthesignaldispersionintwodimensionsallowstoautomaticallyandfinelytrackthedriftsofalargenumberofsignalssimultaneously.Theapplicationofspectralaliasingtothecarbondimensionsallowstoquicklyreachthehighresolutionrequiredtopreciselymeasurevariationsincarbonchemicalshifts.Thepaperextendsthemethodologytothetreatmentofthedatastemmingfromthesimultaneousanalysisofmixturesofcompounds.Italsointroducesmethodstoimprovethenormalizationprocessanddealwithmissingpoints.TheapplicationisnotlimitedtothedeterminationofpKaandcanbereadilyextendedtothedeterminationofotherchemicalconstantsinexperimentswherethecomponentsofthemixturedynamicallycompeteforsubstratesotherthanprotons...