NMR Across The Periodic Table• NMR periodic table NMR active nuclei Spin Receptivity Multiple...

Innovation with Integrity

NMR Across The Periodic TableSpectroscopy beyond H, C, N, P and FENC WorkshopBaltimore, March 7. 2020Clemens Anklin

@canklin

Overview• NMR periodic table

NMR active nuclei Spin Receptivity Multiple Isotopes Referencing

General trends in Multinuclear NMR

• Instrument preparation

Pulse calibration

• Examples

Platinum-195

Boron-11

Arsenic-75

Selenium- 77

Rubidium 85/87

Chlorine 35/37

Sodium-23

Oxygen-17

NMR Periodic table

NMR Periodic TableBasics

• Spin

Known spins = 0, 1/2, 1, 3/2, 5/2, 7/2, 9/2, 5, 6, 7Spin = 0 is not observable by NMRSpin = 1/2 nuclei typically provide narrow lines and often easy to observeSpin > 1/2 nuclei are more difficult and sometimes impossible to observe

• Isotopes

Some elements have multiple NMR active isotopes, some have active and inactive isotopes

NMR is typically not done on radioactive nuclei. Exceptions: 99Tc, 235U, 239Pu

NMR Periodic TableProperties of NMR active nuclei

• Frequency

The NMR frequency of an isotope is determined by its gyromagnetic ratio

• Sensitivity and receptivity

Sensitivity = Sensitivity at equal number of spins

Receptivity = Sensitivity * natural abundance, often relative to 13C.

• Referencing

There are accepted references for almost all isotopes

Referencing to the 1H resonance of TMS is known as Ξ “Chi”

NMR Frequency

𝝂𝝂 =𝜸𝜸𝟐𝟐𝝅𝝅

𝑩𝑩𝟎𝟎

• Frequency

The NMR frequency of an isotope is determined by its gyromagnetic ratio

• The gyromagnetic ratio is a property of every nucleus with a spin ≠ 0

• The actual values can be found in the CRC Handbook for Chemistry and Physics or the derived NMR frequencies in Harris et. Al. Pure Appl.Chem., Vol. 80, No. 1, pp. 59–84, 2008.doi:10.1351/pac200880010059

NMR Frequency• Frequency

NMR active nuclei are well spread over the frequency range.

0

20

40

60

80

100

120

NMR Frequency• Frequency

NMR active nuclei are well spread over the frequency range.

More than half of pairwise differences are less then 1 MHz

0.001

0.01

0.1

1

10

100

19F

203T

l11

9Sn

115S

n14

1Pr

129X

e23

Na

27Al

151E

u45

Sc12

1Sb

185R

e11

5In

165H

o12

7I19

9Hg

209B

i13

9La

138L

a18

1Ta

153E

u50

V85

Rb

169T

m17

6Lu

33S

97M

o67

Zn49

Ti79

Se17

3Yb

109A

g87

Sr10

7Ag

83Kr

149S

m57

Fe16

7Er

187O

s19

7Au

NMR Sensitivity and Receptivity• The NMR sensitivity is defined as

the relative sensitivity of one nucleus when compared to another nucleus at equal number of spins. It is determined by the gyromagnetic ratio and the spin.

• High spin increases sensitivity

0 100 200 300 400 500

0 100 200 300 400 500

NMR Sensitivity and Receptivity• The NMR sensitivity is defined as

the relative sensitivity of one nucleus when compared to another nucleus at equal number of spins. It is determined by the gyromagnetic ratio and the spin.

• Scaled for spin

NMR Sensitivity and Receptivity• The NMR receptivity also takes

into account the natural abundance of a nucleus.

• Receptivity = Sensitivity * natural abundance

1H19F

31P

13C

93Nb

15N

0 100 200 300 400 500

NMR Periodic Table

H He

Li Be B C N O F Ne

Na Mg Al Si P S Cl Ar

K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr

Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe

Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn

Fr Ra Ac Rf Db Sg Bh Hs Mt Ds Rg Cn Nh Fl Mc Lv Ts Og

Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu

Th Pa U Np Pu Am Cm Bk Cf Es F Md No Lr

NMR Periodic Table

H He

Li Be B C N O F Ne







Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr

Unobservable

NMR Periodic Table

H He

Li Be B C N O F Ne








The easy ones: Spin = 1/2

NMR Periodic Table

H He

Li Be B C N O F Ne








Spin = ½, Spin > ½,

NMR Periodic Table

H He

Li Be B C N O F Ne








Spin = ½, Spin > ½, Multiple Isotopes

Multiple Isotopes• Many elements have multiple NMR active isotopes

• Examples: 1H, 2H and 3H , 115Sn, 117Sn and 119Sn, 39K and 41K, 6Li and 7Li

• Which one to choose:

• Spin ½ over anything else

• Natural Abundance the higher the better

• Frequency the higher the better

• Quadrupole Moment the lower the better

Multiple Isotopes• Examples:

Vanadium

Isotope 50 V 51 VFrequency 9.97 26.3Spin 6 7/2Natural Abundance

0.24 % 99.76 %

QuadrupoleMoment

0.21 -5.2x10-2

Multiple Isotopes• Examples:

Molybdenum

Isotope 95 Mo 97 MoFrequency 6.51 6.65Spin 5/2 5/2Natural Abundance

15.9 % 9.55 %

QuadrupoleMoment

-0.015 0.17 From NMR periodic table athttp://chem.ch.huji.ac.il/nmr/techniques/1d/multi.html

NMR Periodic Table

H He

Li Be B C N O F Ne








Paramagnetic nuclei, Difficult nuclei

ReferencingThere are accepted references for almost all isotopes Harris et. Al: Pure Appl.Chem., Vol. 80, No. 1, pp. 59–84, 2008.doi:10.1351/pac200880010059

In many cases it is not possible to add an internal reference to the sample or it is not even possible to acquire a spectrum of the reference compound.

In such cases referencing to the 1H resonance of TMS can be used and is known as Ξ Chi – reference.

AU program = xiref

ReferencingTwo problematic nuclei

13C and 15N

Both have two accepted references

13C uses TMS for organic solvents and DSS/TSP in aqueous solutions

The difference is ~ 2.66 ppm

For 15N the difference is much larger. The references are CH3NO2 and NH3 (liquid).

CH3NO2 is 380.44 ppm from NH3

NH3 is -380.298 ppm from CH3NO2

𝛿𝛿 =𝜈𝜈 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 − 𝜈𝜈(𝑟𝑟𝑠𝑠𝑟𝑟)

𝜈𝜈(𝑟𝑟𝑠𝑠𝑟𝑟)

General trends in multinuclear NMRChemical Shifts

Many nuclei have very large chemical shift ranges. Transition metals can exceed 10’000 ppm

Major influences on chemical shift are:

inner coordination sphere

Oxidation state

Chemical shift (ppm)

hard ligands (O, Cl) soft ligands (C, P)

high oxidation state low oxidation state

The Spectrometer

Hardware requirements

• Many spectrometers are capable of acquiring multinuclear NMR data.

• The range of nuclei accessible will be determined by the probe used.

• When direct observe is of importance multinuclear probes will be the primary choices over inverse detection probes for conventional probes

• Multinculear spectroscopy can also be conducted with cryogenically cooled probes. The limiting factor might be the reduced VT range

• Most of the work can be done in 5mm probes. For direct observation of low receptivity nuclei a 10 mm probe might be helpful

• For many applications a variable temperature accessory is recommended. Some nuclei show very large temperature dependent shifts.

Probes

• BBO, BBFO, SmartProbe and iProbe BBFO

• All these probes have a tuning range from (19F) 31P to 15N or 109 Ag.

• 203/205 Tl is not necessarily included

• For nuclei with a resonance frequency below that of 109Ag, special low range probes are offered.

• For some nuclei such as 27Al, 29Si, 11B, 10B special probes are offered where minimal amounts of these elements are used in the construction of the probe.

Conventional probe range 31P to 109Ag

H He

Li Be B C N O F Ne









Cryogenic probe range 31P to 15N

H He

Li Be B C N O F Ne









Pulse calibration

• Pulse calibration: a bit more complicated than 1H or 13C

• Easy cases:

• A signal is observable in one or a few scans and the relaxation times are not too long.

• Use your standard method of pulse calibration

• Look for the null at 360 degrees

Pulse calibration


• More complex cases:

• Direct observation is hard but satellite signals in 1H spectrum are resolved and reasonably narrow.

• Use “inverse” calibration with decp901H U$lUUNX UUUU&UU

Signal is null at 90 degree X pulse

Pulse calibration



• Direct observation is hard and satellite signals in 1H spectrum are not resolved and somewhat broad. Use the HMQC experiment to determine the 90 degree pulse.

Pulse calibration



• Direct observation is not easy, no coupling to 1H.

• Amplifier power and probe response are continuous over the frequency range. Find a easier nucleus nearby to calibrate the pulse or extrapolate from a known nucleus. For example use 39K to calibrate the pulse for 109Ag, 37Cl can be used for 131Xe etc.

Setting up a new nucleus

• Ready to measure:

• If possible prepare a concentrated sample of the reference compound or another simple, stable well known sample. Harris et. Al: Pure Appl.Chem., Vol. 80, No. 1, pp. 59–84, 2008.

• Try not to use your research sample for set up

And now Examples

Application examples

• NMR of nuclei outside the ones used for organic molecules are used in

• Organometallic and inorganic chemistry

• Material sciences

• Pharma

• Food



• Nuclei measured: 195Pt, 103Rh, 57Fe, 119Sn, 31P, 183W, 109Ag, 199Hg etc

• Coordination chemistry

• Homogeneous catalysis



• Chemical shifts provide information about coordination sphere.

• Coupling constants give information about geometry


• Materials sciences

• Nuclei measured: 29Si, 27Al, 57Fe, 119Sn, 31P, 51V, 7Li, etc

• Lithium has gained a lot of attention for battery research.


• Biomolecules

• Nuclei measured: 113Cd, 109Ag, 199Hg etc

• Metal complexes

• Non active or quadrupolar metals in metallo-proteins can be replaced by spin ½ NMR active nuclei.

• For example Zn can be replaced by Cd

• 1H – 113Cd correlation experiments can be measured,

From S. Forsen FEBS Letters, 1979


• Pharma and Medicine

• Nuclei measured: 23Na, 25Mg, 35Cl, 39K,

• Quality control

• Electrolytes

• Quantification of Na, Cl, K and Mg in infusion solutions.


• Food

• Nuclei measured: 23Na, 25Mg, 31P, 35Cl, 39K,

• Quality control

• Concentration measurements of various salts.

NMR Periodic Table

H He

Li Be B C N O F Ne









Pt

195Pt - Platinum

• Spin = ½

• Nat Abundance = 33.83 %

• Receptivity (rel 13C) = 19.1

• Shift range > 15,000 ppm

• Reference = 1.2 M Na2PtCl 6 in D2O

195Pt - Platinum

• Main problem: Finding the peak

• Literature can help

195Pt - Platinum


• Is there coupling with 1H ?

• If yes use inverse experiments to

• find the peak

• Calibrate the pulse

195Pt - Platinum


• Is there coupling with 1H ?

195Pt - Platinum


• Run a HMQC, with wide sweep in indirect dimension and small flip-angle. Here 8000 ppm and 2 usec pulse.

• Set gradients with gradratio

•

195Pt - Platinum


• Run a HMQC, with wide sweep in indirect dimension and small flip-angle. Here 8000 ppm and 2 usec pulse.

195Pt - Platinum


• Center the signal and reduce sweep in f1

195Pt - Platinum

• Pulse Calibration

• Optimize pulse on HMQC experiment

195Pt - Platinum

• Ready for direct detect 195Pt experiment

• Ca 10 mg, 400 MHz Prodigy Probe

195Pt - Platinum• Multinuclear NMR to characterize metal complexes

• Chemical shifts provide information about the direct environment of the metal

• Coupling constants can proivde information about the configuraitonof the complex.

195Pt - Platinum• Multinuclear NMR to characterize metal complexes

• 31P spectra provide J(31P,195Pt)

• Cis coupling larger than Trans

3518 Hz

2392 Hz

195Pt – Platinum and 119Sn Tin NMR• Multinuclear NMR to follow reactions

• This platinum complex reacts with SnCl2

• The proton spectrum shows a second species forming


• This platinum complex reacts with SnCl2

• The 31P spectrum shows at least 3 species

3518 Hz2392 Hz

2088 Hz


• The new signal show additional peaks

• Ratio of J = = ratio of γ 119Sn and γ 117Sn

• Area matches as well

223.8 Hz

234.7 Hz


• 195Pt NMR confirms the coordination of Sn

• J(119Sn/195Pt) ~ 28000 Hz


• And finally the 119Sn NMR spectrum

NMR Periodic Table

H He

Li Be B C N O F Ne









B

11/10B - Boron

• Boron - 11

• Spin = 3/2


• Receptivity (rel 13C) = 754

• Shift range > 200 ppm

• Reference = BF3 Et2O in CDCl3 15%

• Quadrupolar moment = 4.059*10-2

• Boron - 10

• Spin = 3



• Shift range > 200 ppm

• Reference = BF3 Et2O in CDCl3 15%

• Quadrupolar moment = 8.459*10-2

11/10B - Boron

• Boron - 11

• NaBH4 in D2O BH4 BH3D

11/10B - Boron

• 1H Spectrum

• NaBH4 in D2O

11/10B - Boron

• 1H Spectrum

• NaBH4 in D2O

• 4 x ~ 20= 80

7 x ~ 2.8 = 19.8

11/10B - Boron

• 1H Spectrum

• NaBH4 in D2O

Na11BH4

Na10BH4Na11BH3DNa10BH4

NMR Periodic Table

H He

Li Be B C N O F Ne









As

75As - Arsenic

• Spin = 3/2

• Nat Abundance = 100 %


• Shift range ? ppm

• Reference = 0.5 M NaAsF6 in CD3CN

• Quadrupolar moment = 0.314

75As - Arsenic

• Only highly symmetric molecules give observable lines

• AsO4 or NaAsF6

NMR Periodic Table

H He

Li Be B C N O F Ne









Se

77Se - Selenium

• Spin = 1/2



• Shift range + 2400 to -900 ppm

• Reference = neat (CH3)2Se with trace of C6D6 for lock.

77Se - Selenium

• Relatively easy to measure.

• Most organo-selenium compounds will show nJ(H,Se)

77Se - Selenium



• We can again use the strategy outlined for 195Pt to set up the parameters.

77Se - Selenium



• Proton decoupling is essential for good S/N and sharp lines

without with

77Se - Selenium

• Selenium satellites will also show in experiments such as H,C HSQC

J(C, Se)

J(H, Se)

NMR Periodic Table

H He

Li Be B C N O F Ne









Rb

85/87Rb - Rubidium

• 85Rb

• Spin = 5/2


• Frequency = 9.655 MHz


• Quadrupole mom = 0.26

• Shift range = 30 - -80 ppm

• Reference = RbCl 0.01 M in D2O

• 87Rb

• Spin = 3/2







85/87Rb - Rubidium

• 85Rb Spectrum • 87Rb Spectrum

NMR Periodic Table

H He

Li Be B C N O F Ne









Cl

35/37Cl - Chlorine

• 35Cl

• Spin = 3/2




• Quadrupole mom = -0.1

• Shift range = 1000 - 0 ppm

• Reference = NaCl 0.1 M in D2O

• 37Cl

• Spin = 3/2







35/37Cl - Chlorine

• 35Cl Spectrum • 37Cl Spectrum

35/37Cl - Chlorine

• 35Cl

• Spin = 3/2







• 37Cl

• Spin = 3/2







• 85Rb

• Spin = 5/2







35/37Cl - Chlorine

• 35Cl

• Spin = 3/2







• 85Rb

• Spin = 5/2







35Cl – Chlorine\85Rb - Rubidium

• 35Cl


• 85Rb

• Frequency = 9.655 MHzAt 400 MHz the two signals are only 572 kHz apart. This is a true heteronuclear spectrum

35Cl Signal 85Rb Signal

And now some fun

Soy Sauce NMR

• There are a number of nuclei you can measure in soy sauce but lets focus on one.

Soy Sauce NMR

Soy Sauce NMR

Kikkoman Bragg

EtOH

• Not this one

Soy Sauce NMR

NMR Periodic Table

H He

Li Be B C N O F Ne









Na

23Na - Sodium

• Spin = 3/2

• Nat Abundance = 100 %


• Shift range ~ 110 ppm

• Reference = 0.1 M NaCl in D2O

23Na - Sodium

• Easy Nucleus

• 0.125M NaCl in D2O

23Na - Sodium

• How salty is?

• Unknown Na concentration

• Quantification vs 0.125M NaClsolution

Reference Kikkoman 90% + 10% D200.125 M 1.7 M (1.666M label)

23Na - Sodium

• How salty is?

• Unknown Na concentration

• Quantification vs 0.125M NaClsolution

Reference Bragg 90% + 10% D200.125 M 3.28 M (2.78M label)

Soy Sauce NMR

Do not forget to read the serving size too

And now some more fun

Water NMR

• There are two nuclei you can measure in water, Hydrogen and Oxygen.

• Let’s look at Oxygen

NMR Periodic Table

H He

Li Be B C N O F Ne









O

17O - Oxygen

• Spin = 5/2


• Receptivity (rel 13C) = 0.0611 %

• Shift range - 50 to + 1600 ppm

• Reference = Tap Water

17O - Oxygen

• Different types of Oxygen show large chemical shift differences

• Hydroxyl ~ 0 – 50 ppm

• Carboxylic acids > 200 ppm

• Carbonyls > 500 – 600 ppm

17O - Oxygen

• Some people claim that there is a special healthy form of water called hexagonal water.

• Unhealthy water forms “larger” clusters

• This water can be made with various expensive devices. Or it can be purchased in bottles

17O - Oxygen

• There are claims that Oxygen 17 NMR line width gives information about “structured” or “hexagonal” water.

• Evidence are O17 NMR spectra of water before and after treatment

17O - Oxygen

• So I took a whole bunch of samples that consisted mostly of water and ran O17 NMR.

• Billerica Tap water = 45Hz

17O - Oxygen


• Buffer solution pH 7.4 = 53 Hz

17O - Oxygen


• White wine = 80 Hz

17O - Oxygen


• Diet Coke= 44 Hz

17O - Oxygen


• Soy Sauce = 200 Hz

17O - Oxygen

• What primarily determines the linewidth of the O17 signal ?

• pH• David L. Turner (1980) Proton and deuteron

exchange rates in water measured by oxygen-17 N.M.R., Molecular Physics, 40:4, 949-957,

Conclusion

• There are a lot of interesting nuclei in the periodic table

• Some are easy, some are hard

• Using a standard for preparation is helpful

• Do not be afraid to try something new

Acknowledgement

• The engineers and scientists who build the probes

• My applications colleagues who provided me with material and let me use their instruments

• And all of you for listening

• Check out #IYPT2019 #NMRPT

My NMR Periodic Table

H He

Li Be B C N O F Ne








Innovation with Integrity

NMR Across The Periodic Table• NMR periodic table NMR active nuclei Spin Receptivity Multiple...

Documents

Transcript of NMR Across The Periodic Table• NMR periodic table NMR active nuclei Spin Receptivity Multiple...