Kirill Viktorovich Kovtunov

The present work investigates the potential for enhancing the NMR signals of DNA nucleobases by parahydrogen-based hyperpolarization. Signal amplification by reversible exchange (SABRE) and SABRE in Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) of selected DNA nucleobases is demonstrated with the enhancement (ε) of ¹H, ¹⁵N, and/or ¹³C spins in 3-methyladenine, cytosine, and 6-O-guanine. Solutions of the standard SABRE homogenous catalyst Ir(1,5-cyclooctadeine)(1,3-bis(2,4,6-trimethylphenyl)imidazolium)Cl (“IrIMes”) and a given nucleobase in deuterated ethanol/water solutions yielded low ¹H ε values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of ¹⁵N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. ¹H and ¹⁵N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements (ε~240) of both ¹⁵N atoms for doubly labelled cytosine reveal the preferential binding of specific tautomer(s), thus giving insight into the matching of polarization-transfer and tautomerization time scales. ¹³C enhancements of up to nearly 50-fold were also obtained for this cytosine isotopomer. These efforts may enable the future investigation of processes underlying cellular function and/or dysfunction, including how DNA nucleobase tautomerization influences mismatching in base-pairing.

In this work the mechanism of methylenecyclobutane hydrogenation over titania‐supported Rh, Pt and Pd catalysts was investigated using parahydrogen‐induced polarization (PHIP) technique. It was found that methylenecyclobutane hydrogenation leads to formation of a mixture of reaction products including cyclic (1‐methylcyclobutene, methylcyclobutane), linear (1‐pentene, cis‐2‐pentene, trans‐2‐pentene, pentane) and branched (isoprene, 2‐methyl‐1‐butene, 2‐methyl‐2‐butene, isopentane) compounds. Generally, at lower temperatures (150–350 °C) the major reaction product was methylcyclobutane while higher temperature of 450 °C favors the formation of branched products isoprene, 2‐methyl‐1‐butene and 2‐methyl‐2‐butene. PHIP effects were detected for all reaction products except methylenecyclobutane isomers 1‐methylcyclobutene and isoprene implying that the corresponding compounds can incorporate two atoms from the same parahydrogen molecule in a pairwise manner in the course of the reaction in particular positions. The mechanisms were proposed for the formation of these products based on PHIP results.

We report on a robust and low-cost parahydrogen generator design employing liquid nitrogen as a coolant. The core of the generator consists of catalyst-filled spiral copper tubing, which can be pressurized to 35 atm. Parahydrogen fraction >48% was obtained at 77 K with three nearly identical generators using paramagnetic hydrated iron oxide catalysts. Parahydrogen quantification was performed on the fly via benchtop NMR spectroscopy to monitor the signal from residual orthohydrogen–parahydrogen is NMR silent. This real-time quantification approach was also used to evaluate catalyst activation at up to 1.0 standard liter per minute flow rate. The reported inexpensive device can be employed for a wide range of studies employing parahydrogen as a source of nuclear spin hyperpolarization. To this end, we demonstrate the utility of this parahydrogen generator for hyperpolarization of concentrated sodium [1-¹³C]pyruvate, a metabolic contrast agent under investigation in numerous clinical trials. The reported pilot optimization of SABRE-SHEATH (signal amplification by reversible exchange–shield enables alignment transfer to heteronuclei) hyperpolarization yielded ¹³C signal enhancement of over 14,000-fold at a clinically relevant magnetic field of 1 T corresponding to approximately 1.2% ¹³C polarization—if near 100% parahydrogen would have been employed, the reported value would be tripled to ¹³C polarization of 3.5%.

Many MRI contrast agents formed with the parahydrogen‐induced polarization (PHIP) technique exhibit biocompatible profiles. In the context of respiratory imaging with inhalable molecular contrast agents, the development of nonflammable contrast agents would nonetheless be highly beneficial for the biomedical translation of this sensitive, high‐throughput and affordable hyperpolarization technique. To this end, we assess the hydrogenation kinetics, the polarization levels and the lifetimes of PHIP hyperpolarized products (acids, ethers and esters) at various degrees of fluorine substitution. The results highlight important trends as a function of molecular structure that are instrumental for the design of new, safe contrast agents for in vivo imaging applications of the PHIP technique, with an emphasis on the highly volatile group of ethers used as inhalable anesthetics.