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.