VTNMR

Variable-temperature nuclear magnetic resonance (VT NMR) is a set of NMR techniques that involve recording spectra at different temperatures to observe how molecular processes respond to temperature changes. By altering temperature, VT NMR can reveal dynamic phenomena such as conformational exchange, tautomerism, solvent exchange, and metal-ligand dynamics that are not apparent at a single temperature.

Instrumentation and operation: VT NMR is implemented with a variable-temperature unit in the NMR spectrometer that controls sample temperature during data acquisition. Heating and cooling are achieved through insulated probes using air flow, nitrogen gas, or liquid coolant. Temperature ranges depend on solvent and hardware, but common systems cover roughly -100 °C to +150 °C. Temperature is calibrated with reference standards, and steady-state conditions are typically used for each spectrum. Lock, shimming, and chemical shift referencing must be checked at each temperature.

Data interpretation: Temperature-dependent changes in chemical shifts, line widths, and multiplet patterns reflect exchange processes and population shifts. The coalescence temperature, where two signals merge, provides exchange rates. From temperature dependence of equilibrium constants, one can construct van't Hoff plots to obtain enthalpy and entropy of the process. From kinetic data, Arrhenius or Eyring analyses give activation parameters (ΔH‡, ΔS‡, ΔG‡).

Applications: VT NMR is widely used in organic and inorganic chemistry and in biochemistry to study conformational rearrangements, ring flips, tautomer equilibria, ligand exchange, and thermal unfolding/refolding in proteins or nucleic acids.

Limitations: High viscosity, solvent freezing, sample stability, and temperature gradients can affect spectral quality. Extreme temperatures may alter solvent suppression, viscosity, and relaxation times, reducing sensitivity or complicating interpretation.