Identification of environmentally biodegradable scaffolds for the benign design of quinolones and related substances
Research output: Journal contributions › Journal articles › Research › peer-review
Standard
In: Sustainable Chemistry and Pharmacy, Vol. 31, 100947, 01.04.2023.
Research output: Journal contributions › Journal articles › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Identification of environmentally biodegradable scaffolds for the benign design of quinolones and related substances
AU - Suk, Morten
AU - Lorenz, Stefanie
AU - Kümmerer, Klaus
N1 - Publisher Copyright: © 2022
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Many micropollutants, such as pharmaceuticals and other chemicals, are present globally in the aquatic environment. During effluent treatment and in the environment, transformations result in new chemicals of often unknown structure, fate, and toxicity. The design of chemicals, that can be fully mineralized or broken down into non-hazardous fragments, is considered a green chemistry approach avoiding such problems from the very beginning (“benign by design”). N-heterocycles are central lead scaffolds for many important chemicals and pharmaceuticals such as quinolines, isoquinolines, quinolones, fluoroquinolones, naphthyridones, and quinazolinones. Understanding their environmental biodegradability is mandatory for the design of greener derivatives. While the biodegradability of simple quinolines has already been reported in the literature, information on more complex azaarenes and other N-heterocycles is rather scarce. The goal of this study was to investigate the ready biodegradability of several N-heterocycles to identify biodegradable lead scaffolds. LC-HRMS studies were performed to identify possible metabolites. Out of the 84 tested substances, only 14 were readily biodegradable in either the closed bottle test (OECD 301D) or the manometric respiratory test (OECD 301F). Hydroxylation at the C2 position increased the biodegradation level of the quinolines generally and tolerated even fluorine in the molecule. Moreover, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid has been tested as readily biodegradable. It is an important bioactive lead scaffold with many different applications, i.e., in antibiotics. All other quinolones containing the β-keto-carboxylic acid moiety were persistent, including their bioisosteres. The identified biodegradable scaffolds can be used to design new environmentally biodegradable molecules following green fragment-based design.
AB - Many micropollutants, such as pharmaceuticals and other chemicals, are present globally in the aquatic environment. During effluent treatment and in the environment, transformations result in new chemicals of often unknown structure, fate, and toxicity. The design of chemicals, that can be fully mineralized or broken down into non-hazardous fragments, is considered a green chemistry approach avoiding such problems from the very beginning (“benign by design”). N-heterocycles are central lead scaffolds for many important chemicals and pharmaceuticals such as quinolines, isoquinolines, quinolones, fluoroquinolones, naphthyridones, and quinazolinones. Understanding their environmental biodegradability is mandatory for the design of greener derivatives. While the biodegradability of simple quinolines has already been reported in the literature, information on more complex azaarenes and other N-heterocycles is rather scarce. The goal of this study was to investigate the ready biodegradability of several N-heterocycles to identify biodegradable lead scaffolds. LC-HRMS studies were performed to identify possible metabolites. Out of the 84 tested substances, only 14 were readily biodegradable in either the closed bottle test (OECD 301D) or the manometric respiratory test (OECD 301F). Hydroxylation at the C2 position increased the biodegradation level of the quinolines generally and tolerated even fluorine in the molecule. Moreover, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid has been tested as readily biodegradable. It is an important bioactive lead scaffold with many different applications, i.e., in antibiotics. All other quinolones containing the β-keto-carboxylic acid moiety were persistent, including their bioisosteres. The identified biodegradable scaffolds can be used to design new environmentally biodegradable molecules following green fragment-based design.
KW - Biodegradation
KW - Quinoline
KW - Quinolone
KW - Naphthyridone
KW - Quinazolinone
KW - Fluoroquinolone
KW - Chemistry
UR - http://www.scopus.com/inward/record.url?scp=85145613449&partnerID=8YFLogxK
U2 - 10.1016/j.scp.2022.100947
DO - 10.1016/j.scp.2022.100947
M3 - Journal articles
VL - 31
JO - Sustainable Chemistry and Pharmacy
JF - Sustainable Chemistry and Pharmacy
SN - 2352-5541
M1 - 100947
ER -