TY - JOUR

T1 - Paramagnetic Agents for SE DNP: Synthesis and ESR Characterization of New Lipophilic Derivatives of Finland Trityl

AU - Tormyshev, Victor M

AU - Kuznetsov, Danil A

AU - Raizvikh, Arthur E

AU - Rogozhnikova, Olga Yu

AU - Troitskaya, Tatiana I

AU - Bagryanskaya, Elena G

N1 - This research was funded by RFBR (grant No RSF 24-23-00454) and the Ministry of Education and Science of the Russian Federation (use of experimental setups).

PY - 2025/11/19

Y1 - 2025/11/19

N2 - Triarylmethyl radicals (TAMs) have recently emerged as highly effective polarizing agents in dynamic nuclear polarization (DNP) under viscous conditions, enabling substantial hyperpolarization via the solid-effect (SE) DNP mechanism even at room temperature. A comparable, though less pronounced, enhancement was observed for BDPA radicals embedded in phosphocholine-based lipid bilayers. Given the increasing interest in elucidating the structure and dynamics of biopolymers and their high-molecular-weight assemblies-such as cell membranes-this study focuses on the design, synthesis, and characterization of paramagnetic agents tailored for DNP-based structural biology. To this end, we synthesized a series of TAM derivatives functionalized with lipophilic substituents and characterized their magnetic resonance properties, including isotropic hyperfine interaction (HFI) constants on carbon nuclei and electron spin relaxation times (T1 and Tm) at low temperatures (80 K). Echo-detected EPR spectra and electron spin echo envelope modulations (ESEEM) were recorded for novel TAM incorporated into liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). These low-temperature measurements revealed that the radicals are localized either at the liposome surface or within the lipid bilayer, ensuring optimal accessibility to water molecules. Crucially, the presence of a single cholesterol moiety provides strong noncovalent anchoring within the hydrophobic core of the bilayer. Guided by these findings, we identify an amphiphilic TAM bearing a single cholesterol group and polar carboxyl functionalities as a highly promising candidate for DNP applications in membrane biology, combining efficient polarization transfer, bilayer integration, and aqueous accessibility.

AB - Triarylmethyl radicals (TAMs) have recently emerged as highly effective polarizing agents in dynamic nuclear polarization (DNP) under viscous conditions, enabling substantial hyperpolarization via the solid-effect (SE) DNP mechanism even at room temperature. A comparable, though less pronounced, enhancement was observed for BDPA radicals embedded in phosphocholine-based lipid bilayers. Given the increasing interest in elucidating the structure and dynamics of biopolymers and their high-molecular-weight assemblies-such as cell membranes-this study focuses on the design, synthesis, and characterization of paramagnetic agents tailored for DNP-based structural biology. To this end, we synthesized a series of TAM derivatives functionalized with lipophilic substituents and characterized their magnetic resonance properties, including isotropic hyperfine interaction (HFI) constants on carbon nuclei and electron spin relaxation times (T1 and Tm) at low temperatures (80 K). Echo-detected EPR spectra and electron spin echo envelope modulations (ESEEM) were recorded for novel TAM incorporated into liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). These low-temperature measurements revealed that the radicals are localized either at the liposome surface or within the lipid bilayer, ensuring optimal accessibility to water molecules. Crucially, the presence of a single cholesterol moiety provides strong noncovalent anchoring within the hydrophobic core of the bilayer. Guided by these findings, we identify an amphiphilic TAM bearing a single cholesterol group and polar carboxyl functionalities as a highly promising candidate for DNP applications in membrane biology, combining efficient polarization transfer, bilayer integration, and aqueous accessibility.

KW - Electron Spin Resonance Spectroscopy

KW - Triphenylmethyl Compounds/chemistry

KW - Lipid Bilayers/chemistry

KW - Liposomes/chemistry

KW - Phosphatidylcholines/chemistry

KW - Molecular Structure

U2 - 10.3390/molecules30224463

DO - 10.3390/molecules30224463

M3 - Article

C2 - 41302516

VL - 30

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 22

M1 - 4463

ER -