Chemical and statistical analyses of blotter paper matrix drugs seized in the State of Rio de Janeiro.

Drugs of abuse are psychoactive substances illicitly distributed and used worldwide. In Rio de Janeiro, Brazil, they represent a public health issue and are directly related to several social problems. The recent increase in appearances of new psychoactive substances (NPS), derived from structural modifications of existing psychoactive substances, poses a threat to public health and forensic laboratories worldwide, as little is known about these substances. This study aimed to chemically and geographically map drugs of abuse from blotter papers seized by the Civil Police of Rio de Janeiro State (PCERJ) between 2006 and 2019. High-performance analytical techniques, such as gas chromatography-mass spectrometry (GC-MS) and Orbitrap mass spectrometry (Orbitrap-MS), combined with statistical analyses, were employed to characterize the seized samples. The most common chemical compounds in NPS found in this study were synthetic phenethylamines, i.e., molecules from the 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) and 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) families. Prior to 2014, the majority of seized blotter papers contained lysergic acid diethylamide (LSD) and were concentrated in the Metropolitan region. An upsurge in blotter paper seizures was observed from 2014 to 2017; the most common substances during this time were from the NBOMe family. NBOH compounds emerged in 2016 in coastal regions with high tourism, reaching over 1300 items only in 2017. Only one synthetic cannabinoid was found among the blotter papers seized in Rio de Janeiro between 2006 and 2019. The assembled chemical data and statistical analyses allowed the mapping and monitoring of the chemical profiles of the seized blotter papers, providing a strong foundation for the understanding of the origins and movement of these drugs around the RJ State.

Asymmetric bioreduction of ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess

ABSTRACT This study presents the bioreduction of six β-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 β-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of β-stereogenic-hydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The β-ketoesters series LUMO maps showed that the β-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable β-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the β-ketoesters derivatives separating them into those provided predominantly (R)- or (S)-β-hydroxyesters. The HQSAR models for both (R)- and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of β-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a β-carbon side to the bioconversion to (S)- and (R)-enantiomers.

Asymmetric bioreduction of ß-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess.

This study presents the bioreduction of six ß-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 ß-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of ß-stereogenic-hydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The ß-ketoesters series LUMO maps showed that the ß-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable ß-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the ß-ketoesters derivatives separating them into those provided predominantly (R)- or (S)-ß-hydroxyesters. The HQSAR models for both (R)- and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of ß-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a ß-carbon side to the bioconversion to (S)- and (R)-enantiomers.