Control of reactivity and selectivity of guanidinyliodonium salts toward 18F-Labeling by monitoring of protecting groups: Experiment and theory

Keun Sam Jang, Sung Sik Lee, Young Ho Oh, Sang Hee Lee, Sang Eun Kim, Dong Wook Kim, Byung Chul Lee, Sungyul Lee, David M. Raffel

Research output: Contribution to journalArticle

Abstract

We analyze the effects of protecting group(s) on the efficiency of aromatic 18F-labeling of guanidine-containing radiopharmaceuticals by quantum chemical methods. We elucidate the origin of experimental observations: The fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group exhibits remarkably enhanced reactivity and improved selectivity in contrast to both N,N’-bis-Boc protected guanidine and its isomer in the absence of hydrogen bonding with fluoride ion. We find that this very intriguing observation of reaction rates highly depending on the position of protection by –Boc is due to the effects of strong Coulombic interactions among the ionic species, which allow an optimal position (just above the electropositive carbon and the leaving group) of F in the reaction involving the fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group.

Original languageEnglish
Article number109387
JournalJournal of Fluorine Chemistry
Volume227
DOIs
StatePublished - 1 Nov 2019

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guanidines
Guanidine
Labeling
marking
reactivity
Salts
selectivity
salts
salt
Monitoring
chemical method
monitoring
fluoride
reaction rate
experiment
Experiments
hydrogen
Radiopharmaceuticals
ion
carbon

Keywords

  • Diaryliodonium salts
  • N, N’, N’’, N’’-tetrakis-Boc-protected guanidine
  • Nucleophilic aromatic [F]fluorination
  • Positron emission tomography
  • Radiopharmaceuticals

Cite this

Jang, Keun Sam ; Lee, Sung Sik ; Oh, Young Ho ; Lee, Sang Hee ; Kim, Sang Eun ; Kim, Dong Wook ; Lee, Byung Chul ; Lee, Sungyul ; Raffel, David M. / Control of reactivity and selectivity of guanidinyliodonium salts toward 18F-Labeling by monitoring of protecting groups : Experiment and theory. In: Journal of Fluorine Chemistry. 2019 ; Vol. 227.
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abstract = "We analyze the effects of protecting group(s) on the efficiency of aromatic 18F-labeling of guanidine-containing radiopharmaceuticals by quantum chemical methods. We elucidate the origin of experimental observations: The fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group exhibits remarkably enhanced reactivity and improved selectivity in contrast to both N,N’-bis-Boc protected guanidine and its isomer in the absence of hydrogen bonding with fluoride ion. We find that this very intriguing observation of reaction rates highly depending on the position of protection by –Boc is due to the effects of strong Coulombic interactions among the ionic species, which allow an optimal position (just above the electropositive carbon and the leaving group) of F− in the reaction involving the fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group.",
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Control of reactivity and selectivity of guanidinyliodonium salts toward 18F-Labeling by monitoring of protecting groups : Experiment and theory. / Jang, Keun Sam; Lee, Sung Sik; Oh, Young Ho; Lee, Sang Hee; Kim, Sang Eun; Kim, Dong Wook; Lee, Byung Chul; Lee, Sungyul; Raffel, David M.

In: Journal of Fluorine Chemistry, Vol. 227, 109387, 01.11.2019.

Research output: Contribution to journalArticle

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T1 - Control of reactivity and selectivity of guanidinyliodonium salts toward 18F-Labeling by monitoring of protecting groups

T2 - Experiment and theory

AU - Jang, Keun Sam

AU - Lee, Sung Sik

AU - Oh, Young Ho

AU - Lee, Sang Hee

AU - Kim, Sang Eun

AU - Kim, Dong Wook

AU - Lee, Byung Chul

AU - Lee, Sungyul

AU - Raffel, David M.

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AB - We analyze the effects of protecting group(s) on the efficiency of aromatic 18F-labeling of guanidine-containing radiopharmaceuticals by quantum chemical methods. We elucidate the origin of experimental observations: The fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group exhibits remarkably enhanced reactivity and improved selectivity in contrast to both N,N’-bis-Boc protected guanidine and its isomer in the absence of hydrogen bonding with fluoride ion. We find that this very intriguing observation of reaction rates highly depending on the position of protection by –Boc is due to the effects of strong Coulombic interactions among the ionic species, which allow an optimal position (just above the electropositive carbon and the leaving group) of F− in the reaction involving the fully protected N,N’,N’’,N’’-tetrakis-Boc guanidine group.

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