Homo- A nd Heteronuclear Group 12 Metallothionein Type B Cluster Analogs: Synthesis, Structure, 1H NMR and ESI-MS

Haley M. Brennan; Sophia G. Bunde; Qiaoyue Kuang; Tana V. Palomino; Joshua S. Sacks; Steven M. Berry; Ray John Butcher; John C. Poutsma; Robert D. Pike; Deborah C. Bebout

doi:10.1021/acs.inorgchem.2c03088

Homo- A nd Heteronuclear Group 12 Metallothionein Type B Cluster Analogs: Synthesis, Structure, ¹H NMR and ESI-MS

Haley M. Brennan, Sophia G. Bunde, Qiaoyue Kuang, Tana V. Palomino, Joshua S. Sacks, Steven M. Berry, Ray John Butcher, John C. Poutsma, Robert D. Pike, Deborah C. Bebout

Chemistry & Biochemistry

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M₃S₃and M₄S₅metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M₃S₃cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd₃(L1)₃](ClO₄)₃(1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd₃S₃core. In addition, [Zn₃(L1)₃](ClO₄)₃·4CH₃CN (2·4CH₃CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration ¹H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition "Hg(L1)(ClO₄)" (3). Cryogenic ¹H NMR studies of 3 revealed a J(¹⁹⁹Hg¹H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1-3, as well as mixed-metal [M₂M′(L1)₃(ClO₄)₂]⁺ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.

Original language	English (US)
Pages (from-to)	19857-19869
Number of pages	13
Journal	Inorganic chemistry
Volume	61
Issue number	49
DOIs	https://doi.org/10.1021/acs.inorgchem.2c03088
State	Published - Dec 12 2022

Bibliographical note

Funding Information:
The authors thank both the National Science Foundation (0750119) and the Petroleum Research Fund (40151-B3) for funding initial aspects of this research. We also thank the Camille and Henry Dreyfus Foundation for a Scholar Fellow Award to D.C.B. (SF-02-006) for support of S.M.B. and the research. In addition, we are grateful for William & Mary funding of undergraduate participation and the research. Purchases of the William & Mary SMART Apex II diffractometer and Agilent 400-MR D2 NMR spectrometer were supported by the National Science Foundation (0443345 and 1337295, respectively), as well as William & Mary.

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© 2022 American Chemical Society. All rights reserved.

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10.1021/acs.inorgchem.2c03088

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@article{fd73af14ac004987848a6c049f895dab,

title = "Homo- A nd Heteronuclear Group 12 Metallothionein Type B Cluster Analogs: Synthesis, Structure, 1H NMR and ESI-MS",

abstract = "Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M3S3and M4S5metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M3S3cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd3(L1)3](ClO4)3(1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd3S3core. In addition, [Zn3(L1)3](ClO4)3·4CH3CN (2·4CH3CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration 1H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition {"}Hg(L1)(ClO4){"} (3). Cryogenic 1H NMR studies of 3 revealed a J(199Hg1H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1-3, as well as mixed-metal [M2M′(L1)3(ClO4)2]+ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.",

author = "Brennan, {Haley M.} and Bunde, {Sophia G.} and Qiaoyue Kuang and Palomino, {Tana V.} and Sacks, {Joshua S.} and Berry, {Steven M.} and Butcher, {Ray John} and Poutsma, {John C.} and Pike, {Robert D.} and Bebout, {Deborah C.}",

note = "Funding Information: The authors thank both the National Science Foundation (0750119) and the Petroleum Research Fund (40151-B3) for funding initial aspects of this research. We also thank the Camille and Henry Dreyfus Foundation for a Scholar Fellow Award to D.C.B. (SF-02-006) for support of S.M.B. and the research. In addition, we are grateful for William & Mary funding of undergraduate participation and the research. Purchases of the William & Mary SMART Apex II diffractometer and Agilent 400-MR D2 NMR spectrometer were supported by the National Science Foundation (0443345 and 1337295, respectively), as well as William & Mary. Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",

year = "2022",

month = dec,

day = "12",

doi = "10.1021/acs.inorgchem.2c03088",

language = "English (US)",

volume = "61",

pages = "19857--19869",

journal = "Inorganic chemistry",

issn = "0020-1669",

publisher = "American Chemical Society",

number = "49",

}

TY - JOUR

T1 - Homo- A nd Heteronuclear Group 12 Metallothionein Type B Cluster Analogs

T2 - Synthesis, Structure, 1H NMR and ESI-MS

AU - Brennan, Haley M.

AU - Bunde, Sophia G.

AU - Kuang, Qiaoyue

AU - Palomino, Tana V.

AU - Sacks, Joshua S.

AU - Berry, Steven M.

AU - Butcher, Ray John

AU - Poutsma, John C.

AU - Pike, Robert D.

AU - Bebout, Deborah C.

N1 - Funding Information: The authors thank both the National Science Foundation (0750119) and the Petroleum Research Fund (40151-B3) for funding initial aspects of this research. We also thank the Camille and Henry Dreyfus Foundation for a Scholar Fellow Award to D.C.B. (SF-02-006) for support of S.M.B. and the research. In addition, we are grateful for William & Mary funding of undergraduate participation and the research. Purchases of the William & Mary SMART Apex II diffractometer and Agilent 400-MR D2 NMR spectrometer were supported by the National Science Foundation (0443345 and 1337295, respectively), as well as William & Mary. Publisher Copyright: © 2022 American Chemical Society. All rights reserved.

PY - 2022/12/12

Y1 - 2022/12/12

N2 - Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M3S3and M4S5metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M3S3cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd3(L1)3](ClO4)3(1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd3S3core. In addition, [Zn3(L1)3](ClO4)3·4CH3CN (2·4CH3CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration 1H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition "Hg(L1)(ClO4)" (3). Cryogenic 1H NMR studies of 3 revealed a J(199Hg1H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1-3, as well as mixed-metal [M2M′(L1)3(ClO4)2]+ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.

AB - Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M3S3and M4S5metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M3S3cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd3(L1)3](ClO4)3(1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd3S3core. In addition, [Zn3(L1)3](ClO4)3·4CH3CN (2·4CH3CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration 1H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition "Hg(L1)(ClO4)" (3). Cryogenic 1H NMR studies of 3 revealed a J(199Hg1H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1-3, as well as mixed-metal [M2M′(L1)3(ClO4)2]+ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.

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U2 - 10.1021/acs.inorgchem.2c03088

DO - 10.1021/acs.inorgchem.2c03088

M3 - Article

C2 - 36454194

AN - SCOPUS:85143418559

SN - 0020-1669

VL - 61

SP - 19857

EP - 19869

JO - Inorganic chemistry

JF - Inorganic chemistry

IS - 49

ER -