Tailoring electron-electron coupling network for DNP at high magnetic field and fast MAS

26^th April, 2022

Asif Equbal

Northwestern University, Chicago

University of California, Santa Barbara�

2

Solid Effect (SE)

Overhauser Effect (OE)

Cross Effect (CE)

ω_𝜇w = ω_e ± ω_0n

ω_𝜇w = ω_e

ω_0n = |ω_e1 – ω_e2|

DNP Mechanisms

Key Parameters: T_1e (Temperature, Concentration, Solvent) 2) MW power & frequency 3) e-e coupling network

Thermal Mixing (TM)

ω_0n = |ω_e1 – ω_e2|

flip-flop

flip-flop-flip

ZQ or DQ

microwave Saturation

ZQ or DQ

cross relaxation

Intrinsic Hamiltonian

Inhomogeneous vs. homogeneous broadening

3

What is the most optimum polarization transfer pathway?

How to tune local and global spin concentration to maximize DNP?

0 vs. 6

2 vs. 6

6 vs. 6

15 vs. 6

• OE/CE/TM: Low power requirement
• OE: Requires e-n cross-relaxation (unclear)
• CE/TM: Intrinsic Hamiltonian; e-e helps (designable)
• Trade-off: efficiency vs. number of resonances

CE/TM

vs.

SE/OE

Coupled electron spin system is a better choice

4

Simulated EPR Spectrum of Nitroxide Radical at ~7 T

Basic: Cross-Effect Mechanism

Enhancement ∝ ∆P(e)

𝛚_n = 𝛚_e1 - 𝛚_e2

Thurber et al. J. Chem. Phys. 137, 084508, 2012

Mentink-Vigier et al. J. Magn. Reso. 224, 13-21 

5

2006

TOTAPOL

Chemically tethered

2013

TEKPOL

Bulky

Slow Relaxation

2018

ASYMPOL

Asymmetric

Strong J coupling

2020

TINYPOL

Strong D coupling

2013

AMUPOL

Rigid

Slow Relaxation

2015

TEMTRIPOL

Tethered Mixed Radical

2018

HYTEK

Mixed Radical

Highest DNP

TOTAPOL

TEKPOL

AMUPOL

TINYPOL

ASYMPOL

Evolution of DNP Polarizing Agent

Lund et al. Chemical science 11, 10, 2810, 2020

Mentik-Vigier et al. JACS, 140, 35, 11013–11019, 2018

Song et al JACS, 128, 35, 11385, 2006

Sauvée et al. Angew, 125(41), 11058, 2013

Zagdoun et al, JACS, 135, 34, 12790, 2013

6

• TINYPOL is better at high magnetic field�but far below theoretical maximum, ~660.

• Other Factor?

AMPUPOL

TINYPOL

Optimal electron-electron coupling in a biradical

7

MD simulation

J-coupling distribution

Non-optimum J-coupling

Lund et al. Chemical science 11, 10, 2810, 2020

Why ?

Analysis of TINYPOL

Adiabaticity of e-e crossing is critical to maintain large ΔP_e

Equbal et al. PNMRS 2021, 126, 1

Equbal et al PCCP 2020,22, 13569

Tailor e-e coupling to Magnetic Field

@1000 MHz

@800 MHz

@400 MHz

Recommendation

+ Conformational Rigidity, Molecular Stability, Solubility

Caution! Too large e-e coupling is deleterious.

10

Intermolecular e-e coupling in glassy matrix

Interplay: Microwave Power vs. Spectral Diffusion vs. T_1e Relaxation

• Intramolecular Coupling

Intermolecular Coupling ?

11

ω_0H

ε⁺

ω_0H

ε^-

5 mM, diluted e spin system

DNP using Trityl-OX063

12

SE

TM

SE

High Conc.

• Signatures of TM DNP can be identified using EPR detection

Exploring TM ¹H-DNP in Trityl at High Field

• DNP Enhancement Table

Equbal et al, JPCL, 11, 9, 3718, 2020

• Experimental

Low Cost Synthesizers

13

• DNP Filed/Frequency Profile

• Central positive peak

BDPA: Overhauser DNP

Can et al. JCP, 141, 6, 064202, 2014

BDPA Centre

14

OE: Why? vs. Why Not ?

• Similar DNP Frequency(Field) and MW power profiles.

• Central positive peak

DNP profiles observed in BDPA (OE) are common in CE mechanism

BDPA Centre

Vs.

15

OE: Why? vs. Why Not ?

• Deuteration Effect

• Deuteration changes T1e => Electron Spin Polarization => DNP Profile

• Bulk T1n also changes => possibly via Triple-flip mechanism

• Numerical

• Numerical

Han & coworkers, JPCL 2020

Fully Protonated

Selectively Deuterated

• Numerical

Vs.

Delage-Laurin, Palani et al. JACS, 143(48), 20281, 2021

Kuzhelev et al. JACS, 144, 3, 1164–1168, 2022

Li et al, JPCL, 11, 21, 9195, 2020

Experiment

@ ~9T

EPR Signature of TM: �Asymmetric EPR-line & Hyperpolarization of Electrons in Pump-probe ELDOR

16

Equbal et al, JPCL, 11, 9, 3718, 2020

17

Dipolar Order: Source of Electron Hyperpolarization in ELDOR

Dipolar order detection by EPR confirms cluster states of BDPA and trityl at 20-80 mM concentration.

​

18

Mixing of Zeeman and Dipolar Order Under MW Irradiation

Equbal et al. Unpublished

EPR Signature of Dipolar Order in BDPA => Clustering

19

Pump-probe ELDOR

BDPA

Equbal et al. Unpublished

Signature of

Dipolar Order

DNP

20

• Cross Effect

Tailored Polarizing Agent

There is so much left to learn…. and that is very fascinating

Balance J and D coupling

Conclusion

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Acknowledgement

Prof. Songi Han (UCSB)

Dr. Miranda Li

Kan Tagami

Dr. Sheetal Jain

Dr. Ilia Kaminker

Celeste Tobar

Questions ?

Happening soon!

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