WILL 60MHz WORK FOR YOU?
The emergence of a new class of benchtop, permanent rare-earth magnet NMR spectrometer has sparked a renaissance in 60 MHz NMR Spectroscopy. Although most chemists are familiar with high-field superconducting magnets (>200 MHz), high-resolution, medium-field instruments (20 – 200 MHz), such as the 60 MHz NMReady, are capable of performing many of the jobs currently allocated to high-field instruments (e.g., teaching, research, training and quality control). The primary benefit of such spectrometers is that they do not require weekly cryogen fills, they are compact, portable, accessible, affordable and considerably more robust. There are limitations, however, to lower magnetic fields, and therefore these spectrometers may not be suitable to all applications.
The first limitation of a 60 MHz spectrometer is the sensitivity. A spectrometer’s sensitivity is directly correlated to its field strength, and the resultant Boltzmann distribution of nuclear spins. This means that lower-field spectrometers are inherently less sensitive and will have a lower signal-to-noise ratio (SNR) than high-field counterparts. To offset this fundamental constraint there are two options: (i) increase the concentration of the sample; and (ii) increase the number of scans acquired for each sample. For most customers, we have found that balancing these two options generally ensures optimal data can be acquired (see ibuprofen example below).
As a point of reference, the stacked 1H NMR spectra shown below were acquired for a 0.25 M (250 mM or 50 mg/mL) d-CHCl3 solution of ibuprofen (206.29 g/mol) at various scan numbers (i.e., 4 (18 sec), 8 (35 sec), 16 (1.2 min) and 32 (2.3 min) scans). Although the methine shows some spectral overlap, the spectra are suitable for identification.
We recommend concentrations 0.25 M and higher because data, including accurate integrals, can be acquired in a typical 16 scans at this concentration.
When considering a 60 MHz NMR spectrometer, please review the questions posed below to access the effectiveness of the NMReady for your specific application(s).
What is the molecular weight range of the compounds that you work with?
As a rough guide, NMR at 60 MHz works well on compounds under 500 g/mol. This rule is generally true for compounds that are comprised predominantly by organic small molecules. There are two obvious exceptions to this:
- Your molecules contain a large number of heteroatoms (Si, S, Br etc.) that increase the molecular weight without increasing the number of similar organic moieties (e.g., -CH, -CH2, or –CH3).
- Your material is polymeric. Polymers are made of reoccurring units and afford broad NMR spectra by nature so the resolution is not as important in each spectra.
What resolution is required to complete the analysis at hand?
It is important to note that the term ‘resolution’ refers to two separate measures. First, there is resolution in terms of chemical shift distribution. As heavy or complex molecules will have chemical shift overlap, this is the fundamental limitation to a medium-field instrument.
The second type of resolution refers to the ‘J-couplings’ that can be resolved. The NMReady functions with a line width of 1.4 Hz, so it can resolve the majority of geminal and vicinal couplings. This is suitable for full structural elucidation of molecules with a certain molar mass range, such as those commonly synthesized in academic laboratories. The NMReady has suitable resolution for most reaction monitoring applications, polymer NMR and QA/QC applications.
What is the scale of the reactions you usually perform?
As a corollary, how much material is available for your samples?
If you perform large-scale reactions, are checking starting materials, or running spectra on demonstration compounds in an academic teaching environment then your application is typically not sample limited. Subsequently, we recommend that you make concentrated samples and run a relatively small number of scans. That way you can acquire the data you need in a timely fashion. If you are material and/or solubility limited, lower concentrations are more than acceptable, but it will require more time be committed to data acquisition so a sufficient number of scans can be run to meet your SNR target.
If you are using NMR quantitatively, one must determine what level of error is acceptable in the estimates of peak integrals and adjust the number of scans accordingly. More scans averaged will reduce the error in peak integral estimates. A convenient short cut is, in order to reduce uncertainties by a factor of two, the number of scans will need to be increased by a factor of four (scans and SNR are in a square relationship). In quantitative applications, it is also important to remember that nuclear spins in different chemical environments may have different relaxation times. In order for this not to introduce systematic errors in peak integral estimates, spins should be allowed to relax fully between scans (i.e., a longer interscan delay time may be required).
If you are unsure as to whether or not your application is amenable to the NMReady, please don’t hesitate to contact us for more information.
A note on concentration units… Chemists often use different units for concentration depending on the different applications. Molarity (M = mol/L) is the most common concentration unit, but if one is working with a series of compounds having similar molecular weights, particularly in pharmaceutical research, this will often be expressed in mg/mL. Chemists often refer to molar mass (g/mol) rather than molecular weight (in amu), but those two measures are numerically the same. Biochemists always use millimolar for concentration and Daltons (or kiloDaltons) for molecular mass, but these refer to the same thing (1 Dalton = 1 amu = 1 g/mol). In flow applications, one might use a percentage measure, like volume/volume for liquid solute-solvent samples and use mL/min to represent the flow rate. Esterics, often use molar percentage (or mole fraction), the ratio of the number of moles of a substance in a mixture to the total number of moles. As a point of reference, the mole percent of a standard 25% ethylbenzene sample one might use in a demo is 0.18 (18 mole percent).
