Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides.
摘要：
Heterocycles adjacent to amides can have important influences on molecular conformation due to stereoelectronic effects exerted by the heteroatom. This was shown for imidazole- and thiazole-amides by comparing low energy conformations (ab initio MP2 and DFT calculations), charge distribution, dipole moments, and known crystal structures which support a general principle. Switching a heteroatom from nitrogen to sulfur altered the amide conformation, producing different three-dimensional electrostatic surfaces. Differences were attributed to different dipole and orbital alignments and spectacularly translated into opposing agonist vs antagonist functions in modulating a G-protein coupled receptor for inflammatory protein complement C3a on human macrophages. Influences of the heteroatom were confirmed by locking the amide conformation using fused bicyclic rings. These findings show that stereoelectronic effects of heterocycles modulate molecular conformation and can impart strikingly different biological properties.
展开
DOI：
10.1021/ja506518t
被引量：
年份：
2014
国家科技图书文献中心
(权威机构)
ACS
(全网免费下载)
ACS
万方医学
Semantic Scholar
查看更多
掌桥科研
dx.doi.org
NCBI
NCBI
Europe PMC
ResearchGate
ResearchGate
(全网免费下载)
EBSCO
chtf.stuba.sk
(全网免费下载)
f1000.com
pubfacts.com
学术范
mendeley.com
onacademic.com
mysciencework.com
core.ac.uk
espace.library.uq.edu.au
bmlsearch.com
s3-eu-west-1.amazonaws.com
(全网免费下载)
学术范
(全网免费下载)
ACS
(全网免费下载)
ResearchGate
(全网免费下载)
chtf.stuba.sk
(全网免费下载)
s3-eu-west-1.amazonaws.com
(全网免费下载)
学术范
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
引用走势
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
