New Quantitative Structur e Fragmentation Relationship ttechniques Aapplied in [601203]

New Quantitative Structur e – Fragmentation Relationship ttechniques Aapplied in
Eelectron Iionization Mmass Sspectrometry for the Iidentification of Ssome Aacetalized
Mmonosaccharides
Nicolae Dinc a1,2, Mihai -Cosmin Pascariu3,4 and Eugen Sisu4*

1S SESTEC GmbH, Hilfe Got tes 2, 37539 Bad Grund , Germany
2 “Aurel Vlaicu” Universit y , RO- 310330 Arad, Romania
3 ”Vasile Goldi s “Vasile Goldi ș”” Western University of Arad, RO -310045 Arad, Romania
4 "Victor Babes" University of Medicine and Pharmacy, RO-300041 Timi soara, Romania

4 “Victor Babeș” University of Medici ne and Pharmacy, RO -300041 Timi șoara, Romania

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* Correspondence to : Eugen Șișu , Department of Biochemistry, University of Medicine and
Pharmacy, 2 Eftimie Murgu Sq., RO -300041 Timișoara, Romania . Fax: +[anonimizat] . E-mail:
[anonimizat]

RATIONALE: IWhen f no standards are available for isomeric analyte ’s, isomers or if their
similar mass spectra are not found in spectral libraries, Quantitative Structure -Fragmentation
Relationships (QSFR) offer s algorithms for filtering the most probable structures only through by
mass spectrometry and quantum chemical calculation (QCC) . It is important to extend this type
of chemical structure identification (CSI) to isomers with medium similarity (e.g., di-O-
isopropylidenated monosaccharides ).

METHODS :
We present a new algorithm based on the linear correlation (LCOR) of the enthalpie s of
formation (fH), obtained by QCC, with the ratio of ionic currents (IC) produced in electron
ionization (EI) -– MSmass spectrometry at two ionization energies (IE). The optimal variant , i.e.
the coupling of vertical -LCOR with the fragmentation pattern (FP), was established by the CSI
simulation , in group and individual, ofor five isomers of d i-O-isopropylidenated
monosaccharides . The enthalpies were calculated with the RM1 and PM7 semi -empirical
methods RM1 and PM7 , for some fragments result ed from the considered possible structures
considered .

RESULT S:
The vertical -LCOR –FP coupling used ICs of three common ions, i.e. [M-CH 3•]+, [M -CH 3•-
acetone]+, [M-HO•-2acetone]+, and of four uncommon ions, measured at IE = 10 and 15 eV. The
five structures were correctly allocated to the spectra of the five analytes ’ spectra for the fH
descriptors. Upon individual analysis , the match was obtained for four out of the five analytes ,
searched in a database with descriptors for ten isomeric structure s.

CONCLUSIONS:
The new QSFR algorithm s described here can search de novo the structure , because they does
not require any mass spectra libraries , but only the spectr um of the unknown compound and a
database of fH’s calculated for the ions or for the main fragmentations of the possible
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Introduction

Sugar -based acetals are common substrate s in carbohydrate synthesis chemistry .[1] De Jongh and
Biemann described presented the relationship between EI -mass spectra of O-isopropylidene
derivatives and their molecular weight, ring size and position location , and the stereochemistry of
the parent monosaccharide s precursors , and hence thus the importance of information obtained
by such analyses in the structure elucidation and identification of monosaccharides .[2] Working at
low energy levels for the molecule ionization offers the advantage of simplifying the mass
spectra while at the same tim e providing for a quick examination and interpretation. However,
diagnostic ions have not been identified for each of these isomers , which would allow the
determination of the structure based on the mass spectrum alone , have not been identified for
each of these isomers .[3]
The encouraging results obtained using the Quantitative Structure –Fragmentation Relationship
strategy , aimed towar ds the for chemical structure identification (CSI) for different classes of
isomers with similar mass spectra ,[4–8] prompted us to study, for the first time, the possibility of
applying itthem to a group of five5 isomers of di -O-isopropylidenated monosaccharides. In this
analytical variant the enthalpies of formation of certain common isobaric ions from in the mass
spectra of the possible isomers compensate for the lack of standard spectra in spectra librar ies.
The ordering (ORD ) and linear correlation (LCOR ) algorithms used on this occasion quantif y
and compare the valu es of enthalpies of formation ( fH) obtained by quantum chemical
calculations (QCC ) for some isobaric ions from the electron ionization mass spectra, towith the
corresponding relative intensities. The result of the CSI procedure is provided in the form of lists
of decreasing probabilities calculated for all the isomeric structures .[9,10]
Our paper aims :
– to establish QCC methods suitable for calculating the enthalpy of formation of di-O-
isopropylidenated monosaccharides;
– to verify if the ORD and LCOR algorithms for isobaric ions can be used for the CSI of
isomers with medium similarity of their mass spectra (between 63 –83%, see Table S -1,
Supporting Information ), such as those of di-O-isopropylidenated monosaccharides ; Formatted: Font: Bold
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din Buletin. TREBUIE SCHIMBATA TOPICA FRAZEI
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– to study the influence of the ionization energy on the CSI using isobaric ORD, LCOR and
their coupling ;
– to develop new algorithms for CSI that would use the ratios of intensities of certain main
ions in the analyte’s spectr a obtained at various IEs, and their calculated fH.

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Computational methods

All structures were initially modeled using the HyperChem 8.0.10 software .[11] The starting
neutral molecules were pre -optimized with the “MM+” fo rce field and then optimized with the
RM1 semi -empirical method RM1 .[12] The radical -cations were obtained from these structures
and were finally optimized with the RM1 semi -empirical method RM1 . As for “Spin Pairing”,
RHF operators were used for neutral molecules and cations, while UHF operators were
employed for radicals and radical -cations. The SCF “Convergence limit” was set at 10-5, without
using the “Accelerate convergence” procedure. For geometry optimization and Δ fH calculation,
the “Polak -Ribière (conjugat e gradient)” algorithm was selected with a RMS gradient of 0.01
kcal/(Å ·mol), the molecules being considered in vacuum ( conditions somewhat similar to those
found in EI -MS detectors) .
The MOPAC 2012 software [ 13] was used for the PM7 semi -empirical method PM7 , with
“CHARGE=+1” option for cations and “UHF” option for radicals. The same HyperChem
starting structures were used (the ones obtained after the “Add H & Model Build” command,
with “MM+” pre -optimization). The corresponding “.HIN” files were then convert ed to “.ZMT”
(MOPAC Z -matrix) files and run through the MOPAC interface for geometry optimization and
ΔfH calculation. The line of parameters included “GNORM=0.01”, “BONDS”, “AUX”,
“GRAPHF” and “PDBOUT”, and also the keyword “OPT” whenever possible and the keywords
“SINGLET” (for neutral molecules and cations) or “DOUBLET” (for radical -cations). Two data
sets were obtained, the first one by using the “BFGS ” algorithm, and the second one with tThe
“EF” algorithm was used for geometry optimization , and . Tthe resulting structures were analyzed
with the Jmol software .[14,15]

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REFERENCES

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Rom.) 2002 , 53, 332. Commented [m2]: Consider ca partea aceasta da prea multe
detalii de calcul. Nu avem nevoie de referenti care sa reproduca
aceste calcule si sa gaseasca in materialul suplimentar ca o valoare
folosita de noi este diferita cu 5 sutimi de cea calculata de el. Eu am
incercat sa mai simplific dar sunt sigur ca se m ai poate in continuare.

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Commented [m3]: Cred ca ar trebui sa mentionam si temperatura
(parca cea standard, de 300K ?) pentru care s -au facut toate calculele.
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Commented [m4]: Intrebare : parametrii astia trebuie obligatoriu
mentionati?

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Commented [m5]: Fraza asta presupune ca am folosit ambele
seturi de valor? Sau numai unul? Care dintre ele? De ce? Propun sa o
scoatem pentru ca lucrarea este de spectrometrie de masa.
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contin initialele dupa nume , ordinea ……
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[5] N. Dinc a, E. Sisu, M. Mracec, I. Oprean , O. Sander. Differential mass spectrometry (Diff
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(Bucharest, Rom.) 2004 , 55, 347.
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[11] Hyper Chem™ Professional, Hypercube, Inc., 1115 NW 4th Street, Gainesville, Florida
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[12] G.B. Rocha G.B. , R.O. Freire R.O. , A.M. Simas A.M. , J.J.P. Stewart . J.J.P., RM1: A
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[13] MOPAC2012, James J. P. Stewart, Stewart Computational Chemistry, Colorado Springs,
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[14] J.J.P. Stewart J.J.P. ,. Optimization of parameters for semiempirical meth ods VI: more
modifications to the NDDO approximations and re -optimization of parameters ,. Journal of .
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[15] Jmol: an open -source Java viewer for chemical structures in 3D, http://www.jmol.org/
(March 2015 ).
[16] Patent Number: DE102005028944 -A1, Assignee: C. Bettendorf, Inventor(s): C. Bettendorf,
N. Dinca , 2007 ., http://www.bet2 -soft.de .
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