A new approach to the rational synthesis of MALDI matrices. Keeping the functional groups and their locations but changing the stereochemistry.

MARÍA L. SALUM; ROSA ERRA-BALSELLS

Campignas

Congreso; VBrMass; 2013

The main idea of the approach followed in the present project for the synthesis of several potential MALDI matrix was based on the fact that each cinnamic acid presents two different isomeric forms: trans-cinnamic and cis-cinnamic. The pair of compounds, are called geometric isomers, in which the nature and position of the functional groups in the benzenic moiety is the same but the spatial relation between de substituent present in the alkenic exocyclic group is different (1,2-anti, trans or E; 1,2-gauche, cis or Z). As consequence of this different geometric distribution the bulky substituents present at de vicinal 1,2 positions push the molecule to adopt quite different tridimensional structure. Classically for the trans isomer the thermodynamically more stable conformation is almost flat (bencenic and alkene moieties in the same plane) and for the cis isomer bulky substituents at de 1,2 positions brake the molecular planarity and the total volume and tri dimensional structure of the cis isomer is completely different than those of the trans form. As a reality both isomers are different chemical species whose physical, chemical and photochemical properties can be quite different too. As commercial cinnamic acids (sinapinic, coumaric, ferulic, caffeic, 4-mthoxy-3-hydroxy cinnamic, etc.) are 97-99% the corresponding trans isomer, we decided to find a proper a technique to prepare the corresponding pure cis forms. Thus, after a one-pot preparation method was developed in our laboratory we started the MALDI experiments. Each pair of trans/cis isomers was inspected in comparative way with regard to its mass spectrum and its performance in protein and carbohydrate MALDI MS analysis. For our delaight, cis-cinanmic acids showed in general better performance than the trans isomers. In the field of carbohydrates the different behavior is amazing. Particularly cis-sinapinic acid showed to be an excellent matrix for carbohydrate analysis. Thus, neutral sugars (maltoses, fructanes, cyclodextrins, trehalose) showed in positive ion mode, signals with absolute intensity and signal/noise ratio similar or better than those obtained with gentisic acid. Furthermore, in the field of sulfated sugars, cis-cinnamic acids, particularly cis-sinapinic showed better spectra with a drastic diminishing of number and intensity of signals produced by desulfated fragments; this experiments were conducted comparing the spectra with those got using gentisic acid and nor-harmane as matrix. For better understanding of the relative performance of the new matrices and its trans isomer computational chemistry (molecular modeling) has been used, after optimization of the geometry, to calculate formation energy, proton affinity, volume, surface area, hydration energy, log P and dipolar moment.