Exchangeable proton ENDOR as a probe of the redox-active iron center in activated bleomycin and ferric bleomycinElectronic supplementary information (ESI) available: Scheme 1S showing the dispersion rapid passage Q-band EPR spectra of ABLM and Fe(iii)·BLM. See DOI: 10.1039/c7dt01354j
Activated bleomycin (ABLM) is a drug-Fe( iii )-hydroperoxide complex kinetically competent in DNA attack ( via H4′ abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe( iii )·BLM) is poorly characterized because no observable intermediate produ...
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| creator | Burger, Richard M Grigoryants, Vladimir M Scholes, Charles P |
| description | Activated bleomycin (ABLM) is a drug-Fe(
iii
)-hydroperoxide complex kinetically competent in DNA attack (
via
H4′ abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(
iii
)·BLM) is poorly characterized because no observable intermediate product accumulates. The Fe(
iii
)·BLM formed cryophotolytically from ABLM and kept at 77 K was remarkably similar by EPR and ENDOR criteria to Fe(
iii
)·BLM formed from Fe(
iii
) + BLM solution. The notable ENDOR criteria were the ENDOR frequencies and features of orientation-selected, strongly hyperfine-coupled, exchangeable protons associated with the environs of the iron within |
| doi_str_mv | 10.1039/c7dt01354j |
| format | Article |
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iii
)-hydroperoxide complex kinetically competent in DNA attack (
via
H4′ abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(
iii
)·BLM) is poorly characterized because no observable intermediate product accumulates. The Fe(
iii
)·BLM formed cryophotolytically from ABLM and kept at 77 K was remarkably similar by EPR and ENDOR criteria to Fe(
iii
)·BLM formed from Fe(
iii
) + BLM solution. The notable ENDOR criteria were the ENDOR frequencies and features of orientation-selected, strongly hyperfine-coupled, exchangeable protons associated with the environs of the iron within <3.5 Å of paramagnetic Fe(
iii
) in Fe(
iii
)·BLM and ABLM. Cryophotolytic conversion of activated bleomycin to its ferric bleomycin product in the frozen solid is a sign that the reaction requires only constrained local proton rearrangements. We have characterized the metal-proton distances and orientations of the protons in that rearrangement, especially noting that these protons are of mechanistic importance in the ambient temperature conversion of ABLM to Fe(
iii
)·BLM in concert with a directed radical-forming attack on DNA.
This work establishes the existence of and implies the mechanistic role of specific exchangeable protons near the Fe(
iii
) of activated bleomycin (ABLM).</description><identifier>ISSN: 1477-9226</identifier><identifier>EISSN: 1477-9234</identifier><identifier>DOI: 10.1039/c7dt01354j</identifier><language>eng</language><creationdate>2017-10</creationdate><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Burger, Richard M</creatorcontrib><creatorcontrib>Grigoryants, Vladimir M</creatorcontrib><creatorcontrib>Scholes, Charles P</creatorcontrib><title>Exchangeable proton ENDOR as a probe of the redox-active iron center in activated bleomycin and ferric bleomycinElectronic supplementary information (ESI) available: Scheme 1S showing the dispersion rapid passage Q-band EPR spectra of ABLM and Fe(iii)·BLM. See DOI: 10.1039/c7dt01354j</title><description>Activated bleomycin (ABLM) is a drug-Fe(
iii
)-hydroperoxide complex kinetically competent in DNA attack (
via
H4′ abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(
iii
)·BLM) is poorly characterized because no observable intermediate product accumulates. The Fe(
iii
)·BLM formed cryophotolytically from ABLM and kept at 77 K was remarkably similar by EPR and ENDOR criteria to Fe(
iii
)·BLM formed from Fe(
iii
) + BLM solution. The notable ENDOR criteria were the ENDOR frequencies and features of orientation-selected, strongly hyperfine-coupled, exchangeable protons associated with the environs of the iron within <3.5 Å of paramagnetic Fe(
iii
) in Fe(
iii
)·BLM and ABLM. Cryophotolytic conversion of activated bleomycin to its ferric bleomycin product in the frozen solid is a sign that the reaction requires only constrained local proton rearrangements. We have characterized the metal-proton distances and orientations of the protons in that rearrangement, especially noting that these protons are of mechanistic importance in the ambient temperature conversion of ABLM to Fe(
iii
)·BLM in concert with a directed radical-forming attack on DNA.
This work establishes the existence of and implies the mechanistic role of specific exchangeable protons near the Fe(
iii
) of activated bleomycin (ABLM).</description><issn>1477-9226</issn><issn>1477-9234</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqFkE1PAjEQhlejiZ8X7yTjDQ6L-wESuKkskURFWe9kaGfZkt1t01aEX-bdX2aXGDmY6Gkmz7zzztt63kUYtMMg7l-xHrdBGHc7y33vOOz0en4_ijsHP310feSdGLMMgigKutHxXiNZsxyrBeG8IFBaWllB8jScTAENYE3mBDIDmxNo4nLtI7NiRSC0UzKqLGkQFWwpWuLgjGS5YTWrOGSktWA7mBTErFt1zLwpVVDpLFBvnEcmdYlWONtmko5bgCsURZ1rACnLnRDCFEwu30W12ObhwijSpt7QqAQHhcbgguDFn9e3k-cpOIW7h_UTbm4fHreZRtQUQrQ-PxxoQ0oEw8l4AL8_8cw7zLAwdP5dT73GKHm9u_e1YTOlRemCz3by-P_55V_zmeJZ_AVhipIE</recordid><startdate>20171010</startdate><enddate>20171010</enddate><creator>Burger, Richard M</creator><creator>Grigoryants, Vladimir M</creator><creator>Scholes, Charles P</creator><scope/></search><sort><creationdate>20171010</creationdate><title>Exchangeable proton ENDOR as a probe of the redox-active iron center in activated bleomycin and ferric bleomycinElectronic supplementary information (ESI) available: Scheme 1S showing the dispersion rapid passage Q-band EPR spectra of ABLM and Fe(iii)·BLM. See DOI: 10.1039/c7dt01354j</title><author>Burger, Richard M ; Grigoryants, Vladimir M ; Scholes, Charles P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-rsc_primary_c7dt01354j3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burger, Richard M</creatorcontrib><creatorcontrib>Grigoryants, Vladimir M</creatorcontrib><creatorcontrib>Scholes, Charles P</creatorcontrib></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burger, Richard M</au><au>Grigoryants, Vladimir M</au><au>Scholes, Charles P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exchangeable proton ENDOR as a probe of the redox-active iron center in activated bleomycin and ferric bleomycinElectronic supplementary information (ESI) available: Scheme 1S showing the dispersion rapid passage Q-band EPR spectra of ABLM and Fe(iii)·BLM. See DOI: 10.1039/c7dt01354j</atitle><date>2017-10-10</date><risdate>2017</risdate><volume>46</volume><issue>39</issue><spage>13263</spage><epage>13272</epage><pages>13263-13272</pages><issn>1477-9226</issn><eissn>1477-9234</eissn><abstract>Activated bleomycin (ABLM) is a drug-Fe(
iii
)-hydroperoxide complex kinetically competent in DNA attack (
via
H4′ abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(
iii
)·BLM) is poorly characterized because no observable intermediate product accumulates. The Fe(
iii
)·BLM formed cryophotolytically from ABLM and kept at 77 K was remarkably similar by EPR and ENDOR criteria to Fe(
iii
)·BLM formed from Fe(
iii
) + BLM solution. The notable ENDOR criteria were the ENDOR frequencies and features of orientation-selected, strongly hyperfine-coupled, exchangeable protons associated with the environs of the iron within <3.5 Å of paramagnetic Fe(
iii
) in Fe(
iii
)·BLM and ABLM. Cryophotolytic conversion of activated bleomycin to its ferric bleomycin product in the frozen solid is a sign that the reaction requires only constrained local proton rearrangements. We have characterized the metal-proton distances and orientations of the protons in that rearrangement, especially noting that these protons are of mechanistic importance in the ambient temperature conversion of ABLM to Fe(
iii
)·BLM in concert with a directed radical-forming attack on DNA.
This work establishes the existence of and implies the mechanistic role of specific exchangeable protons near the Fe(
iii
) of activated bleomycin (ABLM).</abstract><doi>10.1039/c7dt01354j</doi><tpages>1</tpages></addata></record> |
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| source | Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| title | Exchangeable proton ENDOR as a probe of the redox-active iron center in activated bleomycin and ferric bleomycinElectronic supplementary information (ESI) available: Scheme 1S showing the dispersion rapid passage Q-band EPR spectra of ABLM and Fe(iii)·BLM. See DOI: 10.1039/c7dt01354j |
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