Design, synthesis, and applications of bio-derived crosslinking monomers for molecular imprinting

Most of the research in the field of molecular imprinting has been focused on the development of new functional monomers, in order to improve the molecular recognition properties afforded by these materials. The role of the crosslinking monomer has often been overlooked, since it is considered an inert component that only provides a scaffold to support the binding sites. However, the crosslinking monomer represents a high percent (80-90%) of the composition of molecularly imprinted polymers (MIPs), which can have a large influence on the MIPs properties. This research addresses the design, synthesis, and applications of new crosslinking monomers for molecular imprinting. Crosslinking monomers containing different polymerizable groups (methacrylate/methacrylamide, methacrylamide/vinylketone, and methacrylate/vinyl ketone) were synthesized and used to prepare MIPs. Key steps in the synthesis of these monomers involved the use enzymatic methodologies to selectively deprotect methyl esters. To avoid an undesirable intramolecular Michael addition, N-methyl-N-methoxy amides derivatives were used as electrophiles to introduce the vinylketone functionality via nucleophilic addition of a Grignard reagent. Enhancement in molecular recognition properties exhibited by MIPs prepared with crosslinking monomers incorporating the amide functionality was attributed to cooperative interactions within the crosslinking with the template molecule, as well as an improved morphology that arises from the reactivity differential of the polymerizable groups. Incorporation of the binding functionality in a crosslinking format allowed to maximize the degree of crosslinking without imposing restrictions on functional group concentrations. An important breakthrough for the simplification of the molecular imprinting process was achieved by the use of a one single monomer, which incorporates an amide functionality for binding the template molecule and the polymerizable groups to form the polymeric network. The advantage of using this single monomer is that there is not need to optimize the functional/crosslinking monomer ratio. The strategy of using functionalized crosslinking monomers derived from natural amino acids, to provide the functional groups for catalytic activity was investigated using a combinatorial approach for fast screening. Finally, modification of biological matrices using bioimprinting methodologies was explored by imprinting a Class I aldolase antibody with an aldol reaction product in order to improve its catalytic activity in organic solvents

Из опыта работы кафедры по организации учебной и воспитательной работы с иностранными студентами

Одна из ярких черт современного высшего образования - его интернационализация. Для Брестского государственного университета имени А.С. Пушкина в процессе интернационализации одним из новых, но перспективных её направлений является экспорт образовательных услуг. Появление в университете данной категории обучающихся (с 2007 г.) внесло коррективы и в организацию учебного процесса, и во внеучебную деятельность

Far-Red and Near-Infrared Seminaphthofluorophores for Targeted Pancreatic Cancer Imaging

Molecular probes that selectively highlight pancreatic cancer (PC) tissue have the potential to improve pancreatic ductal adenocarcinoma (PDAC) margin assessment through the selective highlighting of individual PC cells. Herein, we report a simple and unique family of systematically modified red and near-infrared fluorescent probes that exhibit a field-effect-derived redshift. Two of thirteen probes distributed to the normal mouse pancreas following systemic administration. One selectively accumulated in genetically modified mouse models of PDAC. The probe exhibited intracellular accumulation and enabled visualization of four levels of the structure, including the whole organ, resected tissue, individual cells, and subcellular organelles. In contrast to the small-molecule probes reported previously, it possesses an inherent affinity toward PDAC cells and thus does not require conjugation to any targeting agent. The fluorescent probe can thus promote new strategies not only for precision image-guided surgery, but also for PC detection, monitoring of therapeutic outcomes, and basic research

Seminaphthofluorones are a family of water-soluble, low molecular weight, NIR-emitting fluorophores

A readily accessible new class of near infrared (NIR) molecular probes has been synthesized and evaluated. Specific fluorophores in this unique xanthene based regioisomeric seminaphthofluorone dye series exhibit a combination of desirable characteristics including (i) low molecular weight (339 amu), (ii) aqueous solubility, and (iii) dual excitation and emission from their fluorescent neutral and anionic forms. Importantly, systematic changes in the regiochemistry of benzannulation and the ionizable moieties afford (iv) tunable deep-red to NIR emission from anionic species and (v) enhanced Stokes shifts. Anionic SNAFR-6, exhibiting an unusually large Stokes shift of ≈200 nm (5,014 cm−1) in aqueous buffer, embodies an unprecedented fluorophore that emits NIR fluorescence when excited in the blue/green wavelength region. The successful use of SNAFR-6 in cellular imaging studies demonstrates proof-of-concept that this class of dyes possesses photophysical characteristics that allow their use in practical applications. Notably, each of the new fluorophores described is a minimal template structure for evaluation of their basic spectral properties, which may be further functionalized and optimized yielding concomitant improvements in their photophysical properties

Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.National Institutes of Health (U.S.) (DC010998)National Institutes of Health (U.S.) (NIH DC010231)Harvard College (1780- )Sarah Fuller Foundation for Little Deaf Childre

Optimising the Synthesis and Red–Green–Blue Emission of a Simple Organic Dye

Synthetic dyes have been widely used in supramolecular chemistry not only to probe fundamental chemical interactions but also as components of functional materials. Most current efforts in this regard are directed at designing new host systems for the dyes. Herein we report on the study of a versatile new organic fluorophore. We describe a synthesis which affords improved yields in a convenient one pot procedure. Moreover, a simple method for predicting and controlling the dye’s responses to external stimuli affords a potentially practical method for achieving red–green–blue and concomitant white light generation

Enhanced enantioselectivity of molecularly imprinted polymers formulated with novel cross-linking monomers

To enhance the performance of molecularly imprinted polymers (MIPs), three new cross-linking monomers were designed, synthesized, and evaluated as matrix elements for molecularly imprinted polymers. Hybrid cross-linking monomers incorporating methacrylamide/methacrylate (NOBE), vinyl ketone/methacrylamide (NAG), and vinyl ketone/methacrylate (MVK) polymerizable groups, were synthesized and used to prepare MIPs and compared to a traditional MIP formulated with EGDMA. The resulting macroporous MIPs were evaluated by HPLC for their ability to separate the enantiomers of a chiral template. The MIP formulated with the cross-linking monomer NAG showed the highest enantioselectivity and complete baseline resolution for a racemic mixture of the template. Enhancement in selectivity in this MIP may be attributed to the presence of the amide group which can promote hydrogen bonding via favorable 1,3 donor-acceptor interactions with the template, the morphology of the polymeric material obtained due to differences in reactivity between the polymerizable groups and improved resolution in cavity formation as a consequence of shorter cross-linker size

Development of an aspartic acid-based cross-linking monomer for improved bioseparations

Improved specificity and binding affinity by molecularly imprinted polymers is possible by development of novel functional materials. Furthermore, increasing the cross-link density of imprinted polymers by using cross-linking functional groups was anticipated to improve polymer molecular recognition. A novel cross-linking monomer derived from an L-aspartic acid precursor was synthesized and employed in molecularly imprinted polymers to mimic more closely the scaffolding of proteins, and thus provide more protein-like selectivity. Chromatographie results revealed a more than 7-fold improvement in polymers imprinted using the new monomer versus a traditionally formulated polymer imprinted with methacrylic acid as the functional monomer. © 2002 Kluwer Academic Publishers

Improving the Strategy and Performance of Molecularly Imprinted Polymers Using Cross-Linking Functional Monomers

A new strategy for monomer design has been investigated that combines interactive monomer functionality with a cross-linking format, giving as a result noncovalent molecularly imprinted polymers (MIPs) with improved performance. This strategy was explored under the premise that more functionality could be introduced without suffering performance losses due to reduced cross-linking. While this proved to be correct, equally important contributions to selectivity enhancement at the molecular level by conformation control and diastereomeric complexation were also discovered. Monomers derived from L-serine and L-aspartic acid were synthesized and used to prepare MIPs, with the best performance obtained for the MIP formulated with the serine-based cross-linker (N,O-bis-methacryloyl L-serine, 3), versus the aspartic-acid-based cross-linkers and the traditional methacrylic acid/ethylene glycol dimethacrylate (MAA/EGDMA) formulation. Quantitative structure selectivity relationship (QSSR) studies revealed that the improved performance of 3 was due to three key factors: (1) the cross-linking nature of this monomer; (2) control of conformational flexibility; (3) a strong influence of monomer chirality on enantioselectivity in MIPs