Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with Benign Byproducts

Chadwick R. Powell; Jeffrey C. Foster; Benjamin Okyere; Michelle H. Theus; John B. Matson

doi:10.1021/jacs.6b07204

Therapeutic Delivery of H₂S via COS: Small Molecule and Polymeric Donors with Benign Byproducts

Chadwick R. Powell, Jeffrey C. Foster, Benjamin Okyere, Michelle H. Theus, John B. Matson

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

116 Scopus citations

Abstract

Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H₂S, allowing NTAs to serve as either COS or H₂S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H₂S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H₂S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.

Original language	English
Pages (from-to)	13477-13480
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	138
Issue number	41
DOIs	https://doi.org/10.1021/jacs.6b07204
State	Published - Oct 19 2016
Externally published	Yes

Funding

This work was supported by the NSF (DMR-1454754 to J.B.M.), the Virginia Tech Institute for Critical Technologies and Applied Science (JFC12-256 to J.B.M.), and the National Institutes of Health (NS096281 and NS081623 to M.H.T.). We also thank 3M for support of this work through a Non-Tenured Faculty Award to J.B.M.

Funders	Funder number
National Science Foundation	DMR-1454754
National Institutes of Health	NS081623
National Institute of Neurological Disorders and Stroke	R01NS096281
3M
Institute for Critical Technologies and Applied Science, Virginia Tech	JFC12-256

Access to Document

10.1021/jacs.6b07204

Cite this

@article{307f80d245ce4c299b8701dc835a599b,

title = "Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with Benign Byproducts",

abstract = "Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.",

author = "Powell, {Chadwick R.} and Foster, {Jeffrey C.} and Benjamin Okyere and Theus, {Michelle H.} and Matson, {John B.}",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = oct,

day = "19",

doi = "10.1021/jacs.6b07204",

language = "English",

volume = "138",

pages = "13477--13480",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "41",

}

TY - JOUR

T1 - Therapeutic Delivery of H2S via COS

T2 - Small Molecule and Polymeric Donors with Benign Byproducts

AU - Powell, Chadwick R.

AU - Foster, Jeffrey C.

AU - Okyere, Benjamin

AU - Theus, Michelle H.

AU - Matson, John B.

PY - 2016/10/19

Y1 - 2016/10/19

N2 - Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.

AB - Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.

UR - http://www.scopus.com/inward/record.url?scp=84992214345&partnerID=8YFLogxK

U2 - 10.1021/jacs.6b07204

DO - 10.1021/jacs.6b07204

M3 - Article

C2 - 27715026

AN - SCOPUS:84992214345

SN - 0002-7863

VL - 138

SP - 13477

EP - 13480

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 41

ER -

Therapeutic Delivery of H₂S via COS: Small Molecule and Polymeric Donors with Benign Byproducts

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this