Molecular recognition in water is the basis of numerous biological functions.The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups.This is achieved b...Molecular recognition in water is the basis of numerous biological functions.The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups.This is achieved by bioreceptors for which specific noncovalent interactions are efficiently used in a hydrophobic pocket.In contrast,most synthetic receptors cannot efficiently bind the neutral,polar groups of drug molecules and,thus,often exhibit poor binding selectivity and affinity.In this research,we report a systematic study on the binding behaviors of three types of macrocyclic hosts(amide naphthotubes,cucurbit[7]uril,andβ-cyclodextrin)to 18 model compounds and 13 drug molecules.Our results show that the high desolvation penalty of polar groups of vips is the reason for the relatively low binding affinity of cucurbit[7]uril andβ-cyclodextrin.However,amide naphthotubes with a biomimetic cavity bind efficiently and selectively to organic vips through hydrophobic effects and hydrogen bonding.Drug molecules with multiple polar groups can be better accommodated by these naphthotubes.The anti-configured naphthotube show good biocompatibility according to preliminary cell experiments and is capable of enhancing the water solubility of two poorly soluble drug molecules.Therefore,they may have practical applications in pharmaceutical sciences.展开更多
It is challenging to recognize neutral hydrophilic molecules in water.Effective use of hydrogen bonds in water is generally accepted to be the key to success.In contrast,hydrophobic cavity is usually considered to pla...It is challenging to recognize neutral hydrophilic molecules in water.Effective use of hydrogen bonds in water is generally accepted to be the key to success.In contrast,hydrophobic cavity is usually considered to play an insignificant role or only to provide a nonpolar microenvironment for hydrogen bonds.Herein,we report that hydrophobic cavity alone can also strongly bind neutral,highly hydrophilic molecules in water.We found that cucurbit[n]urils(n=7,8)bind 1,4-dioxane,crown ethers and monosaccharides in water with remarkable affinities.The best binding constant reaches 10^(7) M^(−1) for cucurbit[8]uril,which is higher than its binding affinities to common organic cations.Density functional theory(DFT)calculations and control experiments reveal that the hydrophobic effect is the major contributor to the binding through releasing the cavity water and/or properly occupying the weakly hydrated cavity.However,hydrophobic cavity still prefers nonpolar vips over polar vips with similar size and shape.展开更多
基金This research was financially supported by the National Natural Science Foundation of China(nos.21772083 and 21822104)the Shenzhen Special Funds(KQJSCX20170728162528382 and JCYJ20180504165810828)+3 种基金the Guangdong Provincial Key Laboratory of Catalysis(2020B121201002)the China Postdoctoral Science Foundation(grant no.2019M652183)the University of Macao(MYRG2019-00059-ICMS)the Shenzhen Nobel Prize Scientists Laboratory Project(C17213101)。
文摘Molecular recognition in water is the basis of numerous biological functions.The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups.This is achieved by bioreceptors for which specific noncovalent interactions are efficiently used in a hydrophobic pocket.In contrast,most synthetic receptors cannot efficiently bind the neutral,polar groups of drug molecules and,thus,often exhibit poor binding selectivity and affinity.In this research,we report a systematic study on the binding behaviors of three types of macrocyclic hosts(amide naphthotubes,cucurbit[7]uril,andβ-cyclodextrin)to 18 model compounds and 13 drug molecules.Our results show that the high desolvation penalty of polar groups of vips is the reason for the relatively low binding affinity of cucurbit[7]uril andβ-cyclodextrin.However,amide naphthotubes with a biomimetic cavity bind efficiently and selectively to organic vips through hydrophobic effects and hydrogen bonding.Drug molecules with multiple polar groups can be better accommodated by these naphthotubes.The anti-configured naphthotube show good biocompatibility according to preliminary cell experiments and is capable of enhancing the water solubility of two poorly soluble drug molecules.Therefore,they may have practical applications in pharmaceutical sciences.
基金supported by the National Natural Science Foundation of China(22101125)Shenzhen Science and Technology Innovation Committee(JCYJ20180504165810828)+2 种基金Shenzhen“Pengcheng Scholar”Guangdong High-Level Personnel of Special Support Program(2019TX05C157)Guangdong Provincial Key Laboratory of Catalysis(2020B121201002)。
文摘It is challenging to recognize neutral hydrophilic molecules in water.Effective use of hydrogen bonds in water is generally accepted to be the key to success.In contrast,hydrophobic cavity is usually considered to play an insignificant role or only to provide a nonpolar microenvironment for hydrogen bonds.Herein,we report that hydrophobic cavity alone can also strongly bind neutral,highly hydrophilic molecules in water.We found that cucurbit[n]urils(n=7,8)bind 1,4-dioxane,crown ethers and monosaccharides in water with remarkable affinities.The best binding constant reaches 10^(7) M^(−1) for cucurbit[8]uril,which is higher than its binding affinities to common organic cations.Density functional theory(DFT)calculations and control experiments reveal that the hydrophobic effect is the major contributor to the binding through releasing the cavity water and/or properly occupying the weakly hydrated cavity.However,hydrophobic cavity still prefers nonpolar vips over polar vips with similar size and shape.
