Formulas of High MW Unknown Compounds from Accurate Mass Differences and Ranking of Best Candidates from First Principles

The number of possible candidate formulas for high molecular
weight
unknown compounds (e.g., 7000–8000 Da for common 20-mer oligonucleotides)
by high-resolution mass spectrometry is in the order of several hundred
thousand even at the highest level of experimental accuracy. In demanding
analytical applications involving new chemistries and synthetic routes
where little is known about the chemical nature or mechanisms of formation
of the unknown compounds (e.g., impurities), the generation of a short
list of the most plausible formulas would be highly desirable. Such
an approach has been developed in the current work. The concept of
mass difference from a reference compound is introduced to simplify
the approach and greatly reduce the number of possible formulas. The
approach allows for the generation of candidate formulas by both the
addition and subtraction of atoms to account for all possible molecular
changes from the parent compound. A reduction of 3 orders of magnitude
in the number of possible formulas has been achieved by the approach.
Ranking of the formulas by the product of the sums of the absolute
changes in the total number of all atoms and all heteroatoms in the
proposed difference formula successfully ranked the correct formula
within the top 10 from a list of 200–250 best candidate formulas.
There is a tendency for the impurities to be formed involving the
least change in the number of atoms and heteroatoms. ΔfHo and ΔfG′o values can be used as a complementary
ranking system of the top candidates. The approach is applicable to
unknowns in any other systems of high MW compounds.