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 guests 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 guests 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
Enantioselective recognition in water remains an ongoing challenge in supramolecular chemistry but is routine in nature.Herein,we report the first enantiopure pair of biomimetic macrocyclic receptors with hydrogen bon...Enantioselective recognition in water remains an ongoing challenge in supramolecular chemistry but is routine in nature.Herein,we report the first enantiopure pair of biomimetic macrocyclic receptors with hydrogen bonding donors in their deep hydrophobic cavities.The chiral naphthotubes can be efficiently synthesized through a chirality-directed macrocyclization strategy and are able to discriminate the enantiomers of neutral chiral molecules in water.Density functional theory calculations reveal that the“three-point contact”model effectively explains their enantioselectivity.The differential noncovalent interactions inside the hydrophobic cavity are responsible for the enantioselective recognition.Moreover,these chiral naphthotubes are both fluorescent and circular dichroism(CD)-active.In CD spectroscopy,they have been demonstrated to have the ability to detect nonchromophoric,achiral molecules in water.And,the use of fluorescence spectroscopy has aided in the determination of the enantiomeric excess(ee)values of chiral molecules.The results and conclusions obtained with these chiral biomimetic receptors can be used to better understand enantioselective recognition in biological systems.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 guests over polar guests with similar size and shape.展开更多
Highly selective binding of structurally similar substrates is common for biomolecular recognition,but is often challenging to realize in synthetic hosts.Herein,we report highly selective binding of methyl viologen ov...Highly selective binding of structurally similar substrates is common for biomolecular recognition,but is often challenging to realize in synthetic hosts.Herein,we report highly selective binding of methyl viologen over other analogues by an endo-functionalized naphthobox.X-ray single crystal structure and Density Functional Theory(DFT)calculations revealed that the endo-functionalized groups in the cavity of the naphthobox is important for the high binding selectivity through the formation of multiple C-H…N,C-H…π,andπ…πinteractions with methyl viologen.展开更多
The binding behaviors of three structurally similar and flexible cages to a series of quaternary ammonium ions have been systematically studied.The cage with phenyl sidewalls is new;moreover,its structure and conforma...The binding behaviors of three structurally similar and flexible cages to a series of quaternary ammonium ions have been systematically studied.The cage with phenyl sidewalls is new;moreover,its structure and conformational states have been characterized by NMR;2D NMR,and X-ray crystallography.The results reveal that the three cages show quite high binding affinities and selectivities to different guests.Enthalpy-entropy compensation was invoked to explain the different binding performance.Moreover,a six-component,high-fidelity self-sorting system was successfully constructed by using these cages and three guests.This suggests that conformationally flexible hosts may also achieve high binding affinities and selectivities,which is in contrast to the traditional point of view-only preorganized and rigid hosts are able to do so.This research advocates that conformational flexibility should also be seriously considered in host design.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 guests 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 guests 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(Nos.21772083 and 21822104)the Shenzhen Science and Technology Innovation Committee(KQJSCX2017072816252838 and JCYJ20180504165810828)+1 种基金Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)the Shenzhen Nobel Prize Scientists Laboratory Project(C17213101)。
文摘Enantioselective recognition in water remains an ongoing challenge in supramolecular chemistry but is routine in nature.Herein,we report the first enantiopure pair of biomimetic macrocyclic receptors with hydrogen bonding donors in their deep hydrophobic cavities.The chiral naphthotubes can be efficiently synthesized through a chirality-directed macrocyclization strategy and are able to discriminate the enantiomers of neutral chiral molecules in water.Density functional theory calculations reveal that the“three-point contact”model effectively explains their enantioselectivity.The differential noncovalent interactions inside the hydrophobic cavity are responsible for the enantioselective recognition.Moreover,these chiral naphthotubes are both fluorescent and circular dichroism(CD)-active.In CD spectroscopy,they have been demonstrated to have the ability to detect nonchromophoric,achiral molecules in water.And,the use of fluorescence spectroscopy has aided in the determination of the enantiomeric excess(ee)values of chiral molecules.The results and conclusions obtained with these chiral biomimetic receptors can be used to better understand enantioselective recognition in biological systems.
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 guests over polar guests with similar size and shape.
基金financially supported by the National Natural Science Foundation of China(No.22125105)the Shenzhen Science and Technology Innovation Committee(No.JCYJ20180504165810828)+3 种基金Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)Shenzhen“Pengcheng Scholar”Guangdong High-Level Personnel of Special Support Program(No.2019TX05C157)the Croucher Foundation。
文摘Highly selective binding of structurally similar substrates is common for biomolecular recognition,but is often challenging to realize in synthetic hosts.Herein,we report highly selective binding of methyl viologen over other analogues by an endo-functionalized naphthobox.X-ray single crystal structure and Density Functional Theory(DFT)calculations revealed that the endo-functionalized groups in the cavity of the naphthobox is important for the high binding selectivity through the formation of multiple C-H…N,C-H…π,andπ…πinteractions with methyl viologen.
基金the National Natural Science Foundation of China(No.21801125)the Shenzhen Science and Technology Innovation Committee(No.JCYJ20180504165810828)+2 种基金the Guangdong High-Level Personnel of Special Support Program(No.2019TX05C157)the Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)We thank SUSTech CRF and the Center for Computational Science and Engineering for the technical supports.
文摘The binding behaviors of three structurally similar and flexible cages to a series of quaternary ammonium ions have been systematically studied.The cage with phenyl sidewalls is new;moreover,its structure and conformational states have been characterized by NMR;2D NMR,and X-ray crystallography.The results reveal that the three cages show quite high binding affinities and selectivities to different guests.Enthalpy-entropy compensation was invoked to explain the different binding performance.Moreover,a six-component,high-fidelity self-sorting system was successfully constructed by using these cages and three guests.This suggests that conformationally flexible hosts may also achieve high binding affinities and selectivities,which is in contrast to the traditional point of view-only preorganized and rigid hosts are able to do so.This research advocates that conformational flexibility should also be seriously considered in host design.
