Structural diversity in the host-guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies.

The complexation of the antifolate pemetrexed (PTX) with native cyclodextrins was studied. This process, along with the findings gathered for the structurally related folic acid was treated as a model for exploiting host-guest interactions of this class of guest molecules in the gas phase, in solution and in the solid state. Mass spectrometry was employed for the investigation of the architecture and relative gas-phase stabilities of these supramolecular complexes. The mode of complexation was further tracked by 1D and 2D NMR proving the formation of the exclusion-type complex with α-CD and pseudorotaxane inclusion-type complexes with ß-, and γ-CDs. UV-vis titrations at pH 7.4 gave association constants for the obtained complexes. The stability of the complexes increases in the series: α-CD/PTX < γ-CD/PTX << ß-CD/PTX. The association of PTX with a monomer cyclodextrin equivalent - methyl α-D-glucopyranoside - was investigated for a deeper understanding of the type of host-guest interactions. Solid state studies of PTX/CDs were performed using FTIR-ATR and Raman spectroscopy techniques.

Gas-phase reactions of methyl thiocyanate with aliphatic carbanions - A mass spectrometry and computational study.

RATIONALE: Methyl thiocyanate, like other organic thiocyanates, is a molecule with many electrophilic reactive sites and it has many synthetic applications. For better understanding of the intrinsic reactivity of alkyl thiocyanates against nucleophiles it was important to study gas-phase reactions of methyl thiocyanate with carbanions differing by structure and proton affinity values. METHODS: All experiments were performed using a modified API 365 triple quadrupole mass spectrometer equipped with a TurboIonSpray electrospray ionization (ESI) source. Carbanions were generated in the ESI source by decarboxylation of the respective carboxylic acid anions. Methyl thiocyanate was delivered as a vapor with nitrogen used as a collision gas to the collision cell where the reactions take place. RESULTS: Mass spectra recorded for the gas-phase reactions of five aliphatic carbanions with methyl thiocyanate showed a variety of product ions formed via different reaction mechanisms, depending on the structure and proton affinity of the carbanion. The pathways considered are: SN 2 nucleophilic substitution, cyanophilic reaction, thiophilic reaction and proton transfer, followed in some instances by subsequent transformations. The proposed reaction pathways are supported by density functional theory (DFT) calculations. CONCLUSIONS: Our preliminary experiments showed that mass spectrometry together with quantum chemical calculations is a good tool for studying gas-phase reactions of alkyl thiocyanates with carbanions. In the gas phase all four theoretically possible products can be observed and their formation can be rationalized by the results of the modelling of the reaction energy profiles. Copyright © 2016 John Wiley & Sons, Ltd.