The determination of natural products stereochemistry remains a formidable task.Residual dipolar couplings(RDCs)induced by anisotropic media are a powerful tool for determination of the stereochemistry of organic mole...The determination of natural products stereochemistry remains a formidable task.Residual dipolar couplings(RDCs)induced by anisotropic media are a powerful tool for determination of the stereochemistry of organic molecule in solution.This review will provide a short introduction on RDCs-based methodology for the structural elucidation of natural products.Special attention is given to the current availability of alignment media in organic solvents.The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.Graphical Abstract This review provides a short introduction on RDCs-based methodology for the structural elucidation of natural products.Special attention is given to the current availability of alignment media in organic solvents.The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.展开更多
Residual dipolar couplings(RDCs)are powerful nuclear magnetic resonance(NMR)probes for the structure calculation of biomacromolecules.Typically,an alignment tensor that defines the orientation of the entire molecule r...Residual dipolar couplings(RDCs)are powerful nuclear magnetic resonance(NMR)probes for the structure calculation of biomacromolecules.Typically,an alignment tensor that defines the orientation of the entire molecule relative to the magnetic field is determined either before refinement of individual bond vectors or simultaneously with this refinement.For single-domain proteins this approach works well since all bond vectors can be described within the same coordinate frame,which is given by the alignment tensor.However,novel approaches are sought after for systems where no universal alignment tensor can be used.Here,we present an approach that can be applied to two-domain proteins that enables the calculation of multiple states within each domain as well as with respect to the relative positions of the two domains.展开更多
A sensitivity-enhanced IPAP NMR experiment was described in this paper, whichseparates the ~1H-^(15)N doublets into two different spectra to alleviate the problem of resonanceoverlaps and achieve the accurate measurem...A sensitivity-enhanced IPAP NMR experiment was described in this paper, whichseparates the ~1H-^(15)N doublets into two different spectra to alleviate the problem of resonanceoverlaps and achieve the accurate measurement of J and residual dipolar coupling constants inproteins. This experiment offered 20%―60% sensitivity enhancement over the original IPAPexperiment, and therefore produced more measurable resonances. Pulsed field gradient was used forcoherence selection. Water-flip-back approach was used for water suppression. Thesensitivity-enhanced IPAP experiment was employed in the measurement of ~1J_(NH) and ~1D_(NH)constants of the protein UBC9.展开更多
Measuring the Hamiltonian of dipolar coupled spin systems is usually a difficult task due to the high complexity of their spectra. Currently, molecules with unknown geometrical structure and low symmetry are extremely...Measuring the Hamiltonian of dipolar coupled spin systems is usually a difficult task due to the high complexity of their spectra. Currently, molecules with unknown geometrical structure and low symmetry are extremely tedious or impossible to analyze by sheer spectral fitting. We present a novel method that addresses the problem of spectral analysis and report experimental results of extracting, by spectral fitting, the parameters of an oriented 6-spin system with very low symmetry in structure, without using apriori knowledge or assumptions on the molecular geometry or order parameters. The advantages of our method are achieved with the use of a new spectral analysis algorithm non-assigned frequency optimization of NMR spectra （NAFONS） and by the use of simplified spectra obtained by transition selective pulses. This new method goes beyond the limit of spectral analysis for dipolar coupled spin systems and is helpful for related fields, such as quantum computation and molecular structure analysis.展开更多
The multiple oligopeptides have been regarded as promising alignment media due to their structural diverseness and tendency for self-assembly in solution.Herein,an assembled amphiphilic peptide alignment medium,i.e.,C...The multiple oligopeptides have been regarded as promising alignment media due to their structural diverseness and tendency for self-assembly in solution.Herein,an assembled amphiphilic peptide alignment medium,i.e.,C15eCONH-Phg-Phg-IIIKK-CONH2 with un-natural amino acids for the determination of anisotropic parameters of NMR is introduced.The amphiphilic peptide can be self-assembled at low concentrations in DMSO and is stable and highly homogeneous.The NMR spectrum collected with the addition of the medium had fewer background signals.The utility of the acquired RDC data is demon-strated to determine relative configuration of three natural products,Helminthosporic acid,Estrone,and a-Santonin.展开更多
The characterization of kerogen nanopores is crucial for predicting the geostorage capacity and recoverability of natural gas in unconventional gas shale reservoirs.Towards this end,a powerful technique is presented w...The characterization of kerogen nanopores is crucial for predicting the geostorage capacity and recoverability of natural gas in unconventional gas shale reservoirs.Towards this end,a powerful technique is presented which integrates 2D NMR T_(1)-T_(2) relaxation measurements with molecular dynamics(MD)simulations of hydrocarbons confined in the nanopores of kerogen.The integrated NMR-MD technique is demonstrated using T_(1)-T_(2) measurements of kerogen isolates and organic-rich chalks saturated with heptane,together with MD simulations of heptane completely dissolved in a realistic kerogen model.The NMR-MD results are used to extract the swelling ratio and nanopore size distribution of kerogen as a function of depth in the reservoir.The effects of organic nanoconfinement on the T_(1) relaxation dispersion and T_(2) residual dipolar coupling of heptane are investigated,as well as the effect of downhole effective stress on the kerogen nanopore size as a function of depth and compaction.Potential applications in partially depleted gas shale reservoirs are discussed,including CO_(2) utilization/geostorage,geostorage of green H_(2),and integration of the NMR-MD technique with thermodynamic models for predicting the competitive sorption of gas mixtures in kerogen.展开更多
A new alkylpyrrole derivative,fusariumin A(1),was isolated from the culture broth of the fungus Fusarium sp.The absolute configuration of fuasiumin A has been established as(2'R,3'R)using a combination of RDC(...A new alkylpyrrole derivative,fusariumin A(1),was isolated from the culture broth of the fungus Fusarium sp.The absolute configuration of fuasiumin A has been established as(2'R,3'R)using a combination of RDC(residual dipolar coupling)-based NMR and DFT-supported chiroptical spectroscopy.It is worth to note that in this study without the aid of the RDC analysis,an unambiguous determination of configuration and conformation was not feasible due to the excessive conformational possibilities of this open-chain compound.展开更多
Lanthanide-based spin qubits are intriguing candidates for high-fidelity quantum memories owing to their spin-optical interfaces.Metal-organic frameworks(MOFs)offer promising solid-state platforms to host lanthanide i...Lanthanide-based spin qubits are intriguing candidates for high-fidelity quantum memories owing to their spin-optical interfaces.Metal-organic frameworks(MOFs)offer promising solid-state platforms to host lanthanide ions because their bottom-up synthesis enables rational optimization of both spin coherence and luminescence.Here,we incorporated Nd^(3+)and Gd^(3+)into a La^(3+)-based MOF with various doping levels and examined their qubit performance including the spin relaxation time(T_(1))and phase memory time(Tm).Both Nd^(3+)and Gd^(3+)behave as spin qubits with T_(1) exceeding 1 ms and Tm approaching 2μs at 3.2 K at low doping levels.Variable-temperature spin dynamic studies unveiled spin relaxation and decoherence mechanisms,highlighting the critical roles of spin-phonon coupling and spin-spin dipolar coupling.Accordingly,reducing the spin concentration,spin-orbit coupling strength,and ground spin state improves the qubit performance of lanthanide-based MOFs.These optimization strategies serve as guidelines for the future development of solid-state lanthanide qubits targeting quantum information technologies.展开更多
Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study...Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.展开更多
The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly ...The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly by two techniques： X-ray crystallog- raphy and nuclear magnetic resonance （NMR） spec- troscopy. Because neither X-ray crystallography nor NMR spectroscopy could directly measure the positions of atoms in a biomolecule, algorithms must be designed to compute atom coordinates from the data. One salient feature of most NMR structure computation algorithms is their reliance on stochastic search to find the lowest energy conformations that satisfy the experimentally- derived geometric restraints. However, neither the cor- rectness of the stochastic search has been established nor the errors in the output structures could be quantified. Though there exist exact algorithms to compute struc- tures from angular restraints, similar algorithms that use distance restraints remain to be developed. An important application of structures is rational drug design where protein-ligand docking plays a crit- ical role. In fact, various docking programs that place a compound into the binding site of a target protein have been used routinely by medicinal chemists for both lead identification and optimization. Unfortunately, de- spite ongoing methodological advances and some success stories, the performance of current docking algorithms is still data-dependent. These algorithms formulate the docking problem as a match of two sets of feature points. Both the selection of feature points and the search for the best poses with the minimum scores are accomplished through some stochastic search methods. Both the un- certainty in the scoring function and the limited sam- pling space attained by the stochastic search contribute to their failures. Recently, we have developed two novel docking algorithms： a data-driven docking algorithm and a general docking algorithm that does not rely on experimental data. Our algorithms search the pose space exhaustively with the pose space itself being limited to a set of hierarchical manifolds that represent, respectively, surfaces, curves and points with unique geometric and energetic properties. These algorithms promise to be es- pecially valuable for the docking of fragments and small compounds as well as for virtual screening.展开更多
CONSPECTUS:Acquiring anisotropic NMR parameters such as residual dipolar couplings(RDCs)and residual chemical shift anisotropies(RCSAs)has been demonstrated as a powerful route to elucidate the three-dimensional struc...CONSPECTUS:Acquiring anisotropic NMR parameters such as residual dipolar couplings(RDCs)and residual chemical shift anisotropies(RCSAs)has been demonstrated as a powerful route to elucidate the three-dimensional structure of organic molecules in organic and medicinal chemistry.However,this methodology is somewhat compromised by the limited availability of alignment media,which are indispensable to induce the partial orientation of analytes for anisotropic data acquisition.Given the feature of inherent anisotropy,lyotropic liquid crystals(LLCs)have been documented as excellent candidates to act as alignment media.This Account aims to review the research progress of developing LLCs to obtain anisotropic NMR data.We mainly focus on two complementary LC media,i.e.,two-dimensional(2D)colloidal dispersions and self-assembled peptides,that are generated by a“top-down”approach and“bottom-up”approach,respectively.Our laboratory has been at the forefront of developing 2D colloidal dispersions as alignment media.We first demonstrated the applicability of graphene oxide(GO)LLCs in the RDC-based structural elucidation of small molecules.When used as alignment media,GO LLCs showed a striking feature of no background signals.Clean NMR spectra enable accurate data assignment without disturbances and even effective RDC measurements of rare natural products.To circumvent the limitation that preparing GO LLC media needs tedious solvent exchange to remove nondeuterated solvents for NMR experiments,we subsequently developed MXene LLCs.Different from GO media whose anisotropy would be destroyed after direct freeze-drying,MXene can self-align in the redispersed solution to recover LC behavior.This feature provides great convenience for sample preservation and rapid medium preparation.Another advantage of MXene LLCs over GO media is the applicability to directly measure RDCs of aromatic solutes with no need for chemical modification on MXenes.To complement the 2D colloidal media that are only compatible with strong polar solvents,we further develop supramolecular LLCs.Oligopeptides,due to their mature synthesis strategy,structural designability,and robust self-assembly ability,have been exploited to create supramolecular alignment media in different solvents.We first reported CH3OH-,DMSO-,and multiple solventcompatible peptide media,which show the broad applicability of their corresponding analytes.Meanwhile,the chiral amino acids confer oligopeptide LLCs with potential chirality,and we have demonstrated their relative application of enantiodiscrimination.Arising from the structural diversity of oligopeptides,several distinct LLC media are constructed and applied to measure independent sets of RDCs.This offers an opportunity for de novo structural determination of organic molecules.In light of the good fluidity of these media,analytes can rapidly penetrate the LLC phases for self-alignment,facilitating simple and fast NMR experiments.Moreover,the alignment degree can be easily scaled through varying LC concentrations.This enables precise and accurate data acquisition at an optimal alignment strength.In addition to describing the design and LC preparation,we show the applicability of these weak alignment media for acquiring anisotropic NMR parameters.We hope it can serve as an inspiration source for the exploration of new alignment media,NMR methodology,and related material science.展开更多
基金co-supported by National Natural Science Foundation of China(21572164,U1504207)the Sino-German Center for Research Promotion(GZ1289).
文摘The determination of natural products stereochemistry remains a formidable task.Residual dipolar couplings(RDCs)induced by anisotropic media are a powerful tool for determination of the stereochemistry of organic molecule in solution.This review will provide a short introduction on RDCs-based methodology for the structural elucidation of natural products.Special attention is given to the current availability of alignment media in organic solvents.The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.Graphical Abstract This review provides a short introduction on RDCs-based methodology for the structural elucidation of natural products.Special attention is given to the current availability of alignment media in organic solvents.The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.
基金supported by NIH Grant R01GM130694-01A1,a start-up package by the University of Colorado to B.V.,University of Colorado Cancer Center Support Grant P30 CA046934NIH Biomedical Research Support Shared Grant S10 OD025020-01.
文摘Residual dipolar couplings(RDCs)are powerful nuclear magnetic resonance(NMR)probes for the structure calculation of biomacromolecules.Typically,an alignment tensor that defines the orientation of the entire molecule relative to the magnetic field is determined either before refinement of individual bond vectors or simultaneously with this refinement.For single-domain proteins this approach works well since all bond vectors can be described within the same coordinate frame,which is given by the alignment tensor.However,novel approaches are sought after for systems where no universal alignment tensor can be used.Here,we present an approach that can be applied to two-domain proteins that enables the calculation of multiple states within each domain as well as with respect to the relative positions of the two domains.
文摘A sensitivity-enhanced IPAP NMR experiment was described in this paper, whichseparates the ~1H-^(15)N doublets into two different spectra to alleviate the problem of resonanceoverlaps and achieve the accurate measurement of J and residual dipolar coupling constants inproteins. This experiment offered 20%―60% sensitivity enhancement over the original IPAPexperiment, and therefore produced more measurable resonances. Pulsed field gradient was used forcoherence selection. Water-flip-back approach was used for water suppression. Thesensitivity-enhanced IPAP experiment was employed in the measurement of ~1J_(NH) and ~1D_(NH)constants of the protein UBC9.
文摘Measuring the Hamiltonian of dipolar coupled spin systems is usually a difficult task due to the high complexity of their spectra. Currently, molecules with unknown geometrical structure and low symmetry are extremely tedious or impossible to analyze by sheer spectral fitting. We present a novel method that addresses the problem of spectral analysis and report experimental results of extracting, by spectral fitting, the parameters of an oriented 6-spin system with very low symmetry in structure, without using apriori knowledge or assumptions on the molecular geometry or order parameters. The advantages of our method are achieved with the use of a new spectral analysis algorithm non-assigned frequency optimization of NMR spectra （NAFONS） and by the use of simplified spectra obtained by transition selective pulses. This new method goes beyond the limit of spectral analysis for dipolar coupled spin systems and is helpful for related fields, such as quantum computation and molecular structure analysis.
基金supported by the National Natural Science Foundation of China(21874158)the Science and Technology Major Program of Gansu Province of China(22ZD6FA006 and 23ZDFA015)+1 种基金We are also grateful for the financial support from the Science and Technology Program of Henan Province(232102311180)the foundation for the University Young Key Teacher of Henan Province(2024GGJS116).
文摘The multiple oligopeptides have been regarded as promising alignment media due to their structural diverseness and tendency for self-assembly in solution.Herein,an assembled amphiphilic peptide alignment medium,i.e.,C15eCONH-Phg-Phg-IIIKK-CONH2 with un-natural amino acids for the determination of anisotropic parameters of NMR is introduced.The amphiphilic peptide can be self-assembled at low concentrations in DMSO and is stable and highly homogeneous.The NMR spectrum collected with the addition of the medium had fewer background signals.The utility of the acquired RDC data is demon-strated to determine relative configuration of three natural products,Helminthosporic acid,Estrone,and a-Santonin.
基金Vinegar Technologies LLC,Chevron Energy Technology Company,Rice University Consortium for Processes in Porous Media,and the American Chemical Society Petroleum Research Fund(No.ACS PRF 58859-ND6)for their financial support。
文摘The characterization of kerogen nanopores is crucial for predicting the geostorage capacity and recoverability of natural gas in unconventional gas shale reservoirs.Towards this end,a powerful technique is presented which integrates 2D NMR T_(1)-T_(2) relaxation measurements with molecular dynamics(MD)simulations of hydrocarbons confined in the nanopores of kerogen.The integrated NMR-MD technique is demonstrated using T_(1)-T_(2) measurements of kerogen isolates and organic-rich chalks saturated with heptane,together with MD simulations of heptane completely dissolved in a realistic kerogen model.The NMR-MD results are used to extract the swelling ratio and nanopore size distribution of kerogen as a function of depth in the reservoir.The effects of organic nanoconfinement on the T_(1) relaxation dispersion and T_(2) residual dipolar coupling of heptane are investigated,as well as the effect of downhole effective stress on the kerogen nanopore size as a function of depth and compaction.Potential applications in partially depleted gas shale reservoirs are discussed,including CO_(2) utilization/geostorage,geostorage of green H_(2),and integration of the NMR-MD technique with thermodynamic models for predicting the competitive sorption of gas mixtures in kerogen.
基金Support by the National Natural Science Foundation of China(U1132607)to J.K.L.the DFG(Forschergruppe FOR 934)to C.Gas well as the Chinese/German foundation(GZ1104)to H.S.and C.G.is acknowledged.
文摘A new alkylpyrrole derivative,fusariumin A(1),was isolated from the culture broth of the fungus Fusarium sp.The absolute configuration of fuasiumin A has been established as(2'R,3'R)using a combination of RDC(residual dipolar coupling)-based NMR and DFT-supported chiroptical spectroscopy.It is worth to note that in this study without the aid of the RDC analysis,an unambiguous determination of configuration and conformation was not feasible due to the excessive conformational possibilities of this open-chain compound.
基金supported by the National Natural Science Foundation of China(No.22273078)the Hangzhou Municipal Funding Team of Innovation(TD2022004).
文摘Lanthanide-based spin qubits are intriguing candidates for high-fidelity quantum memories owing to their spin-optical interfaces.Metal-organic frameworks(MOFs)offer promising solid-state platforms to host lanthanide ions because their bottom-up synthesis enables rational optimization of both spin coherence and luminescence.Here,we incorporated Nd^(3+)and Gd^(3+)into a La^(3+)-based MOF with various doping levels and examined their qubit performance including the spin relaxation time(T_(1))and phase memory time(Tm).Both Nd^(3+)and Gd^(3+)behave as spin qubits with T_(1) exceeding 1 ms and Tm approaching 2μs at 3.2 K at low doping levels.Variable-temperature spin dynamic studies unveiled spin relaxation and decoherence mechanisms,highlighting the critical roles of spin-phonon coupling and spin-spin dipolar coupling.Accordingly,reducing the spin concentration,spin-orbit coupling strength,and ground spin state improves the qubit performance of lanthanide-based MOFs.These optimization strategies serve as guidelines for the future development of solid-state lanthanide qubits targeting quantum information technologies.
基金supported by the Leibniz-Forschungsinstitut für Molekulare Pharmakologie(FMP)and the Deutsche Forschungsgemeinschaft(DFG,German Research Foun-dation)under RTG 2473 Bioactive Peptides(392923329)A.F.K.and H.S.under Germany’s Excellence Strategy-EXC 2008/1(UniSysCat,390540038)to C.J.S.and H.S.+2 种基金the National Natural Science Foundation of China(U2006203)to B.-G.W.X.-L.Lsupport from the Taishan Scholars Program(tsqn202306366,China).A.N.-Vthanks National Council for Scien-tific and Technological Development(CNPq)for a research fellowship(309873/2023-1).
文摘Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.
文摘The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly by two techniques： X-ray crystallog- raphy and nuclear magnetic resonance （NMR） spec- troscopy. Because neither X-ray crystallography nor NMR spectroscopy could directly measure the positions of atoms in a biomolecule, algorithms must be designed to compute atom coordinates from the data. One salient feature of most NMR structure computation algorithms is their reliance on stochastic search to find the lowest energy conformations that satisfy the experimentally- derived geometric restraints. However, neither the cor- rectness of the stochastic search has been established nor the errors in the output structures could be quantified. Though there exist exact algorithms to compute struc- tures from angular restraints, similar algorithms that use distance restraints remain to be developed. An important application of structures is rational drug design where protein-ligand docking plays a crit- ical role. In fact, various docking programs that place a compound into the binding site of a target protein have been used routinely by medicinal chemists for both lead identification and optimization. Unfortunately, de- spite ongoing methodological advances and some success stories, the performance of current docking algorithms is still data-dependent. These algorithms formulate the docking problem as a match of two sets of feature points. Both the selection of feature points and the search for the best poses with the minimum scores are accomplished through some stochastic search methods. Both the un- certainty in the scoring function and the limited sam- pling space attained by the stochastic search contribute to their failures. Recently, we have developed two novel docking algorithms： a data-driven docking algorithm and a general docking algorithm that does not rely on experimental data. Our algorithms search the pose space exhaustively with the pose space itself being limited to a set of hierarchical manifolds that represent, respectively, surfaces, curves and points with unique geometric and energetic properties. These algorithms promise to be es- pecially valuable for the docking of fragments and small compounds as well as for virtual screening.
基金supported from the National Natural Science Foundation of China(52273313 and 21874158)the Natural Science Foundation of Hubei province of China(2022CFB466)the Knowledge Innovation Program of Wuhan-Basic Research(2023020201010150).
文摘CONSPECTUS:Acquiring anisotropic NMR parameters such as residual dipolar couplings(RDCs)and residual chemical shift anisotropies(RCSAs)has been demonstrated as a powerful route to elucidate the three-dimensional structure of organic molecules in organic and medicinal chemistry.However,this methodology is somewhat compromised by the limited availability of alignment media,which are indispensable to induce the partial orientation of analytes for anisotropic data acquisition.Given the feature of inherent anisotropy,lyotropic liquid crystals(LLCs)have been documented as excellent candidates to act as alignment media.This Account aims to review the research progress of developing LLCs to obtain anisotropic NMR data.We mainly focus on two complementary LC media,i.e.,two-dimensional(2D)colloidal dispersions and self-assembled peptides,that are generated by a“top-down”approach and“bottom-up”approach,respectively.Our laboratory has been at the forefront of developing 2D colloidal dispersions as alignment media.We first demonstrated the applicability of graphene oxide(GO)LLCs in the RDC-based structural elucidation of small molecules.When used as alignment media,GO LLCs showed a striking feature of no background signals.Clean NMR spectra enable accurate data assignment without disturbances and even effective RDC measurements of rare natural products.To circumvent the limitation that preparing GO LLC media needs tedious solvent exchange to remove nondeuterated solvents for NMR experiments,we subsequently developed MXene LLCs.Different from GO media whose anisotropy would be destroyed after direct freeze-drying,MXene can self-align in the redispersed solution to recover LC behavior.This feature provides great convenience for sample preservation and rapid medium preparation.Another advantage of MXene LLCs over GO media is the applicability to directly measure RDCs of aromatic solutes with no need for chemical modification on MXenes.To complement the 2D colloidal media that are only compatible with strong polar solvents,we further develop supramolecular LLCs.Oligopeptides,due to their mature synthesis strategy,structural designability,and robust self-assembly ability,have been exploited to create supramolecular alignment media in different solvents.We first reported CH3OH-,DMSO-,and multiple solventcompatible peptide media,which show the broad applicability of their corresponding analytes.Meanwhile,the chiral amino acids confer oligopeptide LLCs with potential chirality,and we have demonstrated their relative application of enantiodiscrimination.Arising from the structural diversity of oligopeptides,several distinct LLC media are constructed and applied to measure independent sets of RDCs.This offers an opportunity for de novo structural determination of organic molecules.In light of the good fluidity of these media,analytes can rapidly penetrate the LLC phases for self-alignment,facilitating simple and fast NMR experiments.Moreover,the alignment degree can be easily scaled through varying LC concentrations.This enables precise and accurate data acquisition at an optimal alignment strength.In addition to describing the design and LC preparation,we show the applicability of these weak alignment media for acquiring anisotropic NMR parameters.We hope it can serve as an inspiration source for the exploration of new alignment media,NMR methodology,and related material science.
