The complex amino acid (l-threo)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (l-TFB-TBOA) and its derivatives are privileged compounds for studying the roles of excitatory amino acid transporters (EAATs) in regulation of glutamatergic neurotransmission, animal behavior, and in the pathogenesis of neurological diseases. The wide-spread use of l-TFB-TBOA stems from its high potency of EAAT inhibition and the lack of off-target binding to glutamate receptors. However, one of the main challenges in the evaluation of l-TFB-TBOA and its derivatives is the laborious synthesis of these compounds in stereoisomerically pure form. Here, we report an efficient and step-economic chemoenzymatic route that gives access to enantio- and diastereopure l-TFB-TBOA and its derivatives at multigram scale.
Chitin represents an abundant source of nitrogenous polysaccharides, making it a suitable feedstock for organonitrogen platform chemicals. In particular, furanic compounds, such as 3-acetamido-5-acetylfuran (3A5AF), can be readily obtained. Furans can be further functionalized using a Diels-Alder (DA) cycloaddition with a variety of dienophiles. Herein, we report on the DA of 3A5AF, dihydroxyethyl acetamidofuran (Di-HAF), and several derivatives, with maleimide dienophiles. The formation of exo and endo isomers was monitored in detail, and reactivity trends were established experimentally. Kinetic modeling allowed us to establish a reaction network that included a hydration side reaction involving specifically the exo isomer which affects the overall endo/exo ratio of the reaction. Carbonyl and alkyl hydroxyl substituents on the furans changed the DA rate significantly and shifted the selectivity from the exo to the endo product. Density functional theory (DFT) calculations revealed that the presence of a hydroxyl group leads to a thermodynamically favored endo isomer, evidenced by a decreased ΔGendo. Stronger hydrogen bonding interactions and van der Waals interaction in HMFA-involved TS are responsible for its lower ΔG⧧ values as evidenced by noncovalent interaction analysis, probably promoting the cycloaddition rate in the HMFA case. The activation strain model revealed that a faster cycloaddition rate can be attributed to lower interaction and distortion energies in the HMFA case. Additionally, it is the orbital interactions and electrostatic attractions that favor the endo addition in the HMFA case, while easier structural distortion possibly causes the exo selectivity for 3A5AF. These findings aid the development of synthetic strategies for complex chiral skeletons containing compounds based on chitin-derived building blocks.
Semen traces are considered important pieces of evidence in forensic investigations, especially those involving sexsual offenses. Recently, our research group developed a fluorescence-based technique to accurately determine the age of semen traces. However, the specific compounds resonsible for the fluoresescent behaviour of ageing semens remain unknown. As such, in this exploratory study, the aim is to identify the components associated with the fluorescent behavior of ageing semen traces. In this investigation semen stains and various biofluorophores commonly found in body fluids were left to aged for 0, 2, 4, 7, 14 and 21 days. Subsequently, thin-layer chromatography (TLC) and ultra-performance liquid chromatography (UPLC) mass spectrometry were performed to identify the biofluorophores present in semen. Several contributors to the autofluorescence could be identified in semen stain, these include tryptophan, kynurenine, kynurenic acid, and norharman. The study sheds light on the.
Carboxylated cellulose is an important product on the market, and one of the most well-known examples is carboxymethylcellulose (CMC). However, CMC is prepared by modification of cellulose with the extremely hazardous compound monochloracetic acid. In this project, we want to make a carboxylated cellulose that is a functional equivalent for CMC using a greener process with renewable raw materials derived from levulinic acid. Processes to achieve cellulose with a low and a high carboxylation degree will be designed.
The Cashing Cashew project focuses on isolation and purification of Cashew Nut Shell Liquid (CNSL) from Cashew Nut Shells (CNS) in order to fully utilize this valuable by-product of the cashew nut production. Global cashew nut production is about 4 million mt/ tons/yr. Of the cashew nut, about 70 % is shell that is removed in processing and currently typically burned as a dirty and inefficient fuel or discarded as waste. This is not only creating an environmental issue but also wasting valuable by-products. The shell contains circa 20-30 % brown viscous liquid, Cashew Nut Shell Liquid (CNSL). This natural resin contains valuable chemical components, for example, cardanol, cardol, and anacardic acid. CNSL and its derivatives have several industrial uses as for example biobased additives, polymeric building blocks, and biodiesel. Part of the CNSL can be extracted during the roasting process prior to separating the shell and nut kernel. The shell waste still has a high CNSL concentration that can be isolated by solvents or pressing (expeller). Expeller process is simple and not capital-intensive; therefore it is commonly used. The main disadvantages of the method are the high energy consumption and that 3-5 % oil remains in the press-cake producing harmful gases in burning. Also, the resulting cake is too dense to be further processed to charcoal or other useful application. The objective of this project is to study the purification of the CNSL obtained from pyrolytic isolation to find the most efficient way of making use of the CNSL oil and the total Cashew Nut Shell biomass. An initial evaluation of potential applications is also performed.
Structural colour (SC) is created by light interacting with regular nanostructures in angle-dependent ways resulting in vivid hues. This form of intense colouration offers commercial and industrial benefits over dyes and other pigments. Advantages include durability, efficient use of light, anti-fade properties and the potential to be created from low cost materials (e.g. cellulose fibres). SC is widely found in nature, examples include butterflies, squid, beetles, plants and even bacteria. Flavobacterium IR1 is a Gram-negative, gliding bacterium isolated from Rotterdam harbour. IR1 is able to rapidly self-assemble into a 2D photonic crystal (a form of SC) on hydrated surfaces. Colonies of IR1 are able to display intense, angle-dependent colours when illuminated with white light. The process of assembly from a disordered structure to intense hues, that reflect the ordering of the cells, is possible within 10-20 minutes. This bacterium can be stored long-term by freeze drying and then rapidly activated by hydration. We see these properties as suiting a cellular reporter system quite distinct from those on the market, SC is intended to be “the new Green Fluorescent Protein”. The ability to understand the genomics and genetics of SC is the unique selling point to be exploited in product development. We propose exploiting SC in IR1 to create microbial biosensors to detect, in the first instance, volatile compounds that are damaging to health and the environment over the long term. Examples include petroleum or plastic derivatives that cause cancer, birth defects and allergies, indicate explosives or other insidious hazards. Hoekmine, working with staff and students within the Hogeschool Utrecht and iLab, has developed the tools to do these tasks. We intend to create a freeze-dried disposable product (disposables) that, when rehydrated, allow IR1 strains to sense and report multiple hazardous vapours alerting industries and individuals to threats. The data, visible as brightly coloured patches of bacteria, will be captured and quantified by mobile phone creating a system that can be used in any location by any user without prior training. Access to advice, assay results and other information will be via a custom designed APP. This work will be performed in parallel with the creation of a business plan and market/IP investigation to prepare the ground for seed investment. The vision is to make a widely usable series of tests to allow robust environmental monitoring for all to improve the quality of life. In the future, this technology will be applied to other areas of diagnostics.
