Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators
Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and...
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| Veröffentlicht in: | Journal of biological inorganic chemistry 2024-12, Vol.29 (7), p.785-800 |
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| creator | Konečný, Lukáš Lomozová, Zuzana Karabanovich, Galina Roh, Jaroslav Vávrová, Kateřina Mladěnka, Přemysl |
| description | Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using
o
-cresolphthalein complexone (
o
-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by
o-
CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.
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| doi_str_mv | 10.1007/s00775-024-02078-6 |
| format | Article |
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o
-cresolphthalein complexone (
o
-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by
o-
CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.
Graphical abstract</description><identifier>ISSN: 1432-1327</identifier><identifier>ISSN: 0949-8257</identifier><identifier>EISSN: 1432-1327</identifier><identifier>DOI: 10.1007/s00775-024-02078-6</identifier><identifier>PMID: 39422739</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Calcium - analysis ; Calcium - metabolism ; Calcium homeostasis ; Chelating agents ; Chelating Agents - chemistry ; Chelation ; Drug Evaluation, Preclinical - methods ; Homeostasis ; Humans ; Ions ; Life Sciences ; Magnesium ; Magnesium - chemistry ; Metals ; Microbiology ; Original Paper ; Platelet aggregation ; Platelet Aggregation - drug effects ; Spectrophotometry ; Structure-Activity Relationship</subject><ispartof>Journal of biological inorganic chemistry, 2024-12, Vol.29 (7), p.785-800</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Springer Nature B.V. 2024</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-dfd19f4dfcffc0654076cb1e08c2c1c60a9bae28e037df73f114c217fd2b50693</cites><orcidid>0000-0002-6076-6900</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00775-024-02078-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00775-024-02078-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39422739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Konečný, Lukáš</creatorcontrib><creatorcontrib>Lomozová, Zuzana</creatorcontrib><creatorcontrib>Karabanovich, Galina</creatorcontrib><creatorcontrib>Roh, Jaroslav</creatorcontrib><creatorcontrib>Vávrová, Kateřina</creatorcontrib><creatorcontrib>Mladěnka, Přemysl</creatorcontrib><title>Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators</title><title>Journal of biological inorganic chemistry</title><addtitle>J Biol Inorg Chem</addtitle><addtitle>J Biol Inorg Chem</addtitle><description>Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using
o
-cresolphthalein complexone (
o
-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by
o-
CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.
Graphical abstract</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Calcium - analysis</subject><subject>Calcium - metabolism</subject><subject>Calcium homeostasis</subject><subject>Chelating agents</subject><subject>Chelating Agents - chemistry</subject><subject>Chelation</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Ions</subject><subject>Life Sciences</subject><subject>Magnesium</subject><subject>Magnesium - chemistry</subject><subject>Metals</subject><subject>Microbiology</subject><subject>Original Paper</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Spectrophotometry</subject><subject>Structure-Activity Relationship</subject><issn>1432-1327</issn><issn>0949-8257</issn><issn>1432-1327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kU1v3CAQhlHUKF_tH-ihQuqlFycM2GCfqipqPqRIkaL0jDCGXVIbtmAnyr8Pzm432xx6AGY0z7zD6EXoM5BTIEScpXyJqiC0zIeIuuB76AhKRgtgVHzYiQ_RcUoPhBBWQXWADllTUipYc4T8nVq5Dg9mXIYO2xBx0tEY7_wCB4vbMC6xVr1204CVz6BaeJPmTC9Nr0YXPH5yMxSGlYou5Tz3UcC_fXjys7DqN2yI6SPat6pP5tPmPUG_Ln7en18VN7eX1-c_bgrNKj4Wne2gsWVntbWa8KokgusWDKk11aA5UU2rDK0NYaKzglmAUlMQtqNtRXjDTtD3te5qagfTaePHqHq5im5Q8VkG5eS_Fe-WchEeJQBnNRNlVvi2UYjhz2TSKAeXtOl75U2YkmQAoml4TeZhX9-hD2GKPu-XqZI1FeVipuia0jGkFI3d_gaInP2Uaz9l9lO--il5bvqyu8e25a-BGWBrIOWSX5j4Nvs_si8dca1P</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Konečný, Lukáš</creator><creator>Lomozová, Zuzana</creator><creator>Karabanovich, Galina</creator><creator>Roh, Jaroslav</creator><creator>Vávrová, Kateřina</creator><creator>Mladěnka, Přemysl</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6076-6900</orcidid></search><sort><creationdate>20241201</creationdate><title>Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators</title><author>Konečný, Lukáš ; Lomozová, Zuzana ; Karabanovich, Galina ; Roh, Jaroslav ; Vávrová, Kateřina ; Mladěnka, Přemysl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-dfd19f4dfcffc0654076cb1e08c2c1c60a9bae28e037df73f114c217fd2b50693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Calcium - analysis</topic><topic>Calcium - metabolism</topic><topic>Calcium homeostasis</topic><topic>Chelating agents</topic><topic>Chelating Agents - chemistry</topic><topic>Chelation</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Ions</topic><topic>Life Sciences</topic><topic>Magnesium</topic><topic>Magnesium - chemistry</topic><topic>Metals</topic><topic>Microbiology</topic><topic>Original Paper</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Spectrophotometry</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Konečný, Lukáš</creatorcontrib><creatorcontrib>Lomozová, Zuzana</creatorcontrib><creatorcontrib>Karabanovich, Galina</creatorcontrib><creatorcontrib>Roh, Jaroslav</creatorcontrib><creatorcontrib>Vávrová, Kateřina</creatorcontrib><creatorcontrib>Mladěnka, Přemysl</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of biological inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Konečný, Lukáš</au><au>Lomozová, Zuzana</au><au>Karabanovich, Galina</au><au>Roh, Jaroslav</au><au>Vávrová, Kateřina</au><au>Mladěnka, Přemysl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators</atitle><jtitle>Journal of biological inorganic chemistry</jtitle><stitle>J Biol Inorg Chem</stitle><addtitle>J Biol Inorg Chem</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>29</volume><issue>7</issue><spage>785</spage><epage>800</epage><pages>785-800</pages><issn>1432-1327</issn><issn>0949-8257</issn><eissn>1432-1327</eissn><abstract>Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using
o
-cresolphthalein complexone (
o
-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by
o-
CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.
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| subjects | Biochemistry Biomedical and Life Sciences Blood Platelets - drug effects Blood Platelets - metabolism Calcium - analysis Calcium - metabolism Calcium homeostasis Chelating agents Chelating Agents - chemistry Chelation Drug Evaluation, Preclinical - methods Homeostasis Humans Ions Life Sciences Magnesium Magnesium - chemistry Metals Microbiology Original Paper Platelet aggregation Platelet Aggregation - drug effects Spectrophotometry Structure-Activity Relationship |
| title | Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators |
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