Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange
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 demon...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/3/1198 |
| _version_ | 1797623738890452992 |
|---|---|
| author | Bryce E. Kidd Max E. Gemeinhardt Jamil A. Mashni Jonathan L. Gesiorski Liana B. Bales Miranda N. Limbach Roman V. Shchepin Kirill V. Kovtunov Igor V. Koptyug Eduard Y. Chekmenev Boyd M. Goodson |
| author_facet | Bryce E. Kidd Max E. Gemeinhardt Jamil A. Mashni Jonathan L. Gesiorski Liana B. Bales Miranda N. Limbach Roman V. Shchepin Kirill V. Kovtunov Igor V. Koptyug Eduard Y. Chekmenev Boyd M. Goodson |
| author_sort | Bryce E. Kidd |
| collection | DOAJ |
| description | 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 (<i>ε</i>) of <sup>1</sup>H, <sup>15</sup>N, and/or <sup>13</sup>C 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 <sup>1</sup>H <i>ε</i> values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of <sup>15</sup>N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. <sup>1</sup>H and <sup>15</sup>N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements (<i>ε</i>~240) of both <sup>15</sup>N 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. <sup>13</sup>C 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. |
| first_indexed | 2024-03-11T09:33:04Z |
| format | Article |
| id | doaj.art-1e13714edefe44779f75301d1727ca52 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:33:04Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1e13714edefe44779f75301d1727ca522023-11-16T17:29:02ZengMDPI AGMolecules1420-30492023-01-01283119810.3390/molecules28031198Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible ExchangeBryce E. Kidd0Max E. Gemeinhardt1Jamil A. Mashni2Jonathan L. Gesiorski3Liana B. Bales4Miranda N. Limbach5Roman V. Shchepin6Kirill V. Kovtunov7Igor V. Koptyug8Eduard Y. Chekmenev9Boyd M. Goodson10School of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USADepartment of Chemistry, Biology, and Health Sciences, South Dakota School of Mines & Technology, Rapid City, SD 57701, USAInternational Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, RussiaInternational Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, RussiaDepartment of Chemistry, Integrative Biosciences (Ibio), Karmanos Cancer Institute (KCI) Wayne State University, Detroit, MI 48202, USASchool of Chemical & Biomolecular Sciences, Southern Illinois University, Carbondale, IL 62901, USAThe 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 (<i>ε</i>) of <sup>1</sup>H, <sup>15</sup>N, and/or <sup>13</sup>C 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 <sup>1</sup>H <i>ε</i> values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of <sup>15</sup>N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. <sup>1</sup>H and <sup>15</sup>N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements (<i>ε</i>~240) of both <sup>15</sup>N 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. <sup>13</sup>C 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.https://www.mdpi.com/1420-3049/28/3/1198hyperpolarizationSABREPHIPnucleic acidsNMR & MRI |
| spellingShingle | Bryce E. Kidd Max E. Gemeinhardt Jamil A. Mashni Jonathan L. Gesiorski Liana B. Bales Miranda N. Limbach Roman V. Shchepin Kirill V. Kovtunov Igor V. Koptyug Eduard Y. Chekmenev Boyd M. Goodson Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange Molecules hyperpolarization SABRE PHIP nucleic acids NMR & MRI |
| title | Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange |
| title_full | Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange |
| title_fullStr | Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange |
| title_full_unstemmed | Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange |
| title_short | Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange |
| title_sort | hyperpolarizing dna nucleobases via nmr signal amplification by reversible exchange |
| topic | hyperpolarization SABRE PHIP nucleic acids NMR & MRI |
| url | https://www.mdpi.com/1420-3049/28/3/1198 |
| work_keys_str_mv | AT bryceekidd hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT maxegemeinhardt hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT jamilamashni hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT jonathanlgesiorski hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT lianabbales hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT mirandanlimbach hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT romanvshchepin hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT kirillvkovtunov hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT igorvkoptyug hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT eduardychekmenev hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange AT boydmgoodson hyperpolarizingdnanucleobasesvianmrsignalamplificationbyreversibleexchange |