title: Like polarity ion/ion reactions enable the investigation of specific metal interactions in nucleic acids and their noncovalent assemblies.
abstract: A rare example of ion/ion reaction between species of like polarity was shown to take place during the transfer of metal cations from nucleic acid substrates to chelating agents in the gas phase. Gaseous anionic reactants were generated from separate solutions of analyte and chelator by using a dual nanospray setup. The respective multiply charged ions shared the same path and were allowed to react for a predetermined interval in an rf-only hexapole before high-resolution analysis by Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Efficient transfer of sodium and magnesium ions was readily observed with significant reduction of the nonspecific adducts that are typically associated with decreased sensitivity and resolution in the analysis of nucleic acid samples. Metal cations were abstracted from the initial analyte without being replaced by protons, in a process that was clearly dependent on the concentration of chelator in the auxiliary emitter and on the time spent by the reactants in the hexapole element. A survey of the properties of selected anionic chelators showed that their known affinity for a target cation in solution was more critical than their maximum anionic charge in determining the outcome of the transfer process. The analysis of selected assemblies requiring divalent cations to preserve their structural integrity and functional properties demonstrated that ion/ion reactions were clearly capable of discriminating between nonspecific interactions and specific coordination based on transfer susceptibility. These examples demonstrated that the ability to selectively eliminate nonspecific adducts in the gas phase, after the desolvation process is complete, offers a unique opportunity for studying specific metal binding in biological systems without resorting to separation procedures that may adversely affect the position of binding equilibria in solution and disrupt the assemblies under investigation.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21228, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Turner
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Monti
authors.forename: Daniele
authors.initials: D
authors.lastname: Fabris
mesh_terms: D002614:Chelating Agents / Q000737:chemistry; D005740:Gases / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D008024:Ligands; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry*; D044367:Phase Transition; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002614:Chelating Agents; D005740:Gases; D007477:Ions; D008024:Ligands; D008670:Metals; D009696:Nucleic Acids
references.citation: Nucleic Acids Res. 2006 Mar 06;34(5):1305-16
references.pmid: 16522643
references.citation: Mass Spectrom Rev. 1996;15(2):67-138
references.pmid: 27082318
references.citation: J Mol Biol. 2007 Jan 12;365(2):396-410
references.pmid: 17070549
references.citation: Anal Chem. 2007 Oct 15;79(20):7916-9
references.pmid: 17867655
references.citation: J Am Soc Mass Spectrom. 1995 Jan;6(1):27-39
references.pmid: 24222058
references.citation: Science. 1996 Sep 20;273(5282):1678-85
references.pmid: 8781224
references.citation: Curr Opin Struct Biol. 2003 Jun;13(3):325-33
references.pmid: 12831883
references.citation: RNA. 2004 Mar;10(3):335-43
references.pmid: 14970378
references.citation: Nucleic Acids Res. 2001 Nov 1;29(21):E103-3
references.pmid: 11691940
references.citation: RNA. 2004 Sep;10(9):1366-79
references.pmid: 15317974
references.citation: Rapid Commun Mass Spectrom. 1999;13(10):954-62
references.pmid: 10353227
references.citation: Protein Sci. 1992 May;1(5):563-74
references.pmid: 1304355
references.citation: J Am Soc Mass Spectrom. 1996 Aug;7(8):697-706
references.pmid: 24203563
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2318-22
references.pmid: 7534419
references.citation: Mass Spectrom Rev. 2005 Nov-Dec;24(6):931-58
references.pmid: 15706594
references.citation: Rapid Commun Mass Spectrom. 1994 May;8(5):394-400
references.pmid: 8025335
references.citation: Rapid Commun Mass Spectrom. 1992 Mar;6(3):159-65
references.pmid: 1372835
references.citation: J Am Soc Mass Spectrom. 1996 Sep;7(9):923-9
references.pmid: 24203606
references.citation: J Mol Biol. 2003 May 30;329(2):229-38
references.pmid: 12758072
references.citation: J Membr Biol. 2004 Jun 1;199(3):163-71
references.pmid: 15457373
references.citation: J Am Soc Mass Spectrom. 2001 Jul;12(7):780-5
references.pmid: 11444599
references.citation: Anal Chem. 1996 Sep 15;68(18):3295-9
references.pmid: 8797389
references.citation: J Am Soc Mass Spectrom. 2005 Nov;16(11):1750-6
references.pmid: 16182558
references.citation: Rapid Commun Mass Spectrom. 1992 Dec;6(12):771-6
references.pmid: 1283705
references.citation: J Mol Biol. 1997 Nov 14;273(5):1020-31
references.pmid: 9367788
references.citation: Annu Rev Biochem. 1967;36:407-48
references.pmid: 18257727
references.citation: Nucleic Acids Res. 1993 Jul 11;21(14):3191-6
references.pmid: 8341593
references.citation: Anal Chem. 1998 Sep 1;70(17):3553-6
references.pmid: 9737206
references.citation: Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):790-3
references.pmid: 8381533
references.citation: J Phys Chem A. 2005 Apr 28;109(16):3608-16
references.pmid: 16568152
references.citation: J Am Soc Mass Spectrom. 2004 Apr;15(4):607-15
references.pmid: 15047065
references.citation: Biochemistry. 1995 Jan 31;34(4):1376-85
references.pmid: 7827085
references.citation: Anal Chem. 1996 Nov 15;68(22):4026-32
references.pmid: 8916454
references.citation: Anal Chem. 1996 Jan 1;68(1):1-8
references.pmid: 8779426
references.citation: Biophys J. 1993 Nov;65(5):1916-28
references.pmid: 8298021
references.citation: Cell. 1999 May 14;97(4):491-502
references.pmid: 10338213
references.citation: Rapid Commun Mass Spectrom. 1998;12(23):1957-61
references.pmid: 9842743
references.citation: Annu Rev Phys Chem. 1999;50:517-36
references.pmid: 10575730
references.citation: Nat Biotechnol. 1997 May;15(5):427-31
references.pmid: 9131619
references.citation: J Am Soc Mass Spectrom. 1992 Sep;3(6):624-30
references.pmid: 24234566
references.citation: J Mol Biol. 2002 May 10;318(4):963-73
references.pmid: 12054794
references.citation: Nat Rev Mol Cell Biol. 2005 May;6(5):399-412
references.pmid: 15956979
references.citation: J Am Chem Soc. 2003 Oct 15;125(41):12404-5
references.pmid: 14531672
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4262-6
references.pmid: 9113977
references.citation: Science. 1993 Aug 6;261(5122):709-14
references.pmid: 7688142
references.citation: J Mol Biol. 2007 Jun 8;369(3):812-28
references.pmid: 17466332
references.citation: Mass Spectrom Rev. 1998 Nov-Dec;17(6):369-407
references.pmid: 10360331
references.citation: J Am Chem Soc. 2003 Jun 18;125(24):7238-49
references.pmid: 12797797
references.citation: J Mol Biol. 1990 Dec 5;216(3):689-99
references.pmid: 2124274
references.citation: J Mass Spectrom. 2000 Jul;35(7):784-9
references.pmid: 10934432
references.citation: Biochemistry. 2003 Sep 16;42(36):10736-45
references.pmid: 12962498