Efficient Separation of Nucleic Acids with Different Secondary Structures by Metal–Organic Frameworks

Abstract

We report the use of metal–organic frameworks (MOFs) for the selective separation of nucleic acids (DNA and RNA) with different secondary structures through size, shape, length, and capability of conformational transition. Three MOFs with precisely controlled pore environments, Co-IRMOF-74-II, -III, and -IV, composed of Co2+ and organic linkers (II, III, and IV), respectively, were used for the inclusion of nucleic acid into their pores from the solution. This was proven to be a spontaneous process from disordered free state to restricted ordered state via circular dichroism (CD) spectroscopy. Three critical factors were identified for their inclusion: (1) size selection induced by steric hindrance, (2) conformation transition energy selection induced by stability, and (3) molecular weight selection. These selection rules were used to extract nucleic acids with flexible and unstable secondary structures from complex mixtures of multiple nucleic acids, leaving those with rigid and stable secondary structures in the mother liquor. This provides the possibility to separate and enrich nucleic acids in bulk through their different structure feature, which is highly desirable in genome-wide structural measurement of nucleic acids. Unlike methods that rely on specific binding antibodies or ligand, this MOF method is capable of selecting all kinds of nucleic acids with similar secondary structure features; therefore, it is suitable for the handling of a large variety and quantity of nucleic acids at the same time. This method also has the potential to gather information about the folding stability of biomolecules with secondary structures.

Revisiting molecular adsorption: unconventional uptake of polymer chains from solution into sub-nanoporous media

“…Most recently, this polymer insertion phenomenon has been employed to discriminate between different polymer structures. [44][45][46][47][48] In this manner, MOFs recognize minute differences in polymer architectures upon an insertion event, thus allowing precise polymer separation. 47,48 However, a full understanding of the polymer insertion mechanism remains incomplete despite such prospective applications in the realm of materials science.…”

Emerging Nanoporous Materials for Biomolecule Separation

“…These selection rules were used to extract nucleic acids with flexible and unstable secondary structures from complex mixtures of multiple nucleic acids, leaving those with rigid and stable secondary structures in the mother liquor. [135] For example, The imprinted protein-binding cavity provides both shape and chemical complementarity for protein recognition. Reproduced with permission.…”

“…These selection rules were used to extract nucleic acids with flexible and unstable secondary structures from complex mixtures of multiple nucleic acids, leaving those with rigid and stable secondary structures in the mother liquor. [ 135 ] For example, nucleic acids with unstable secondary structures can still enter the pores of MOFs through a molecular conformation change from unstable state to conformation transition state (ΔG 1 ) and then uptake state (unstable, solid red line), although their size is bigger than the pore of MOFs. However, nucleic acids must overcome a much higher energy barrier (ΔG 2 ) to enter the pores of MOFs if they have stable secondary structures (stable, dotted red line) ( Figure a).…”

“…After a centrifugation process, the nucleic acids are separated. Reproduced with permission [135]. Copyright 2020, American Chemical Society.…”

Metal-Organic Frameworks for Macromolecular Recognition and Separation

“…39 DNA and proteins were also loaded in the 1D channels of MOF-74 for their protection and separation. 18,43,44 A major topic that should be discussed here concerns the molecular mechanism of polymer intercalation. Although polymer adsorption on solid surfaces has been ll extensively studied due to its technological importance in industrial applications such as adhesion, coating, painting, and composites, 45 polymer intercalation into microporous materials is not very well known.…”