Synthesized Model Compounds Research Articles

A simple TICT/ICT based molecular probe exhibiting ratiometric fluorescence Turn-On response in selective detection of Cu2+

The work reported herein describes photophysical behavior of a new fluorescent probe APDA. The probe exhibited sensitivity for Cu2+ ion in 80% aqueous acetonitrile medium. Probe shows dual emission due to TICT and ICT states and upon interaction with different metal ions Cu2+ induces hydrolysis of imine bond to rejuvenate aldehyde derivative with ratiometric “turn–On” fluorescence response, through ICT state while emission due to TICT state get diminished. Similarly, the synthesized model compound ADA under similar experimental condition supported hydrolysis of imine bond in the presence of copper. Jobs plot analysis, based on emission titration data suggested a 1:1 binding stoichiometry between probe APDA and Cu2+ ion. The limit of detection (LOD) was found to be 4.4 × 10-8 M (44 nM). The probe has been applied on test paper strip to detect Cu2+ ion with naked-eye sensitive response. Also, the cell imaging studies revealed the potential applicability of probe to detect Cu2+ ion in live cells. The mechanism of sensing was confirmed by 1H, 13C NMR, FTIR and mass spectrometry data analysis.

Biomimetic oxidative copolymerization of hydroxystilbenes and monolignols

Hydroxystilbenes are a class of polyphenolic compounds that behave as lignin monomers participating in radical coupling reactions during the lignification. Here, we report the synthesis and characterization of various artificial copolymers of monolignols and hydroxystilbenes, as well as low-molecular-mass compounds, to obtain the mechanistic insights into their incorporation into the lignin polymer. Integrating the hydroxystilbenes, resveratrol and piceatannol, into monolignol polymerization in vitro, using horseradish peroxidase to generate phenolic radicals, produced synthetic lignins [dehydrogenation polymers (DHPs)]. Copolymerization of hydroxystilbenes with monolignols, especially sinapyl alcohol, by in vitro peroxidases notably improved the reactivity of monolignols and resulted in substantial yields of synthetic lignin polymers. The resulting DHPs were analyzed using two-dimensional NMR and 19 synthesized model compounds to confirm the presence of hydroxystilbene structures in the lignin polymer. The cross-coupled DHPs confirmed both resveratrol and piceatannol as authentic monomers participating in the oxidative radical coupling reactions during polymerization.

Biophysical profiling of synthetic ultra-long tear film lipids

The tear film lipid layer (TFLL) is a unique biological membrane of importance to the maintenance of ocular surface health. The underlying factors at play, e.g. the ability to retard evaporation and offer protection from the environment, are all closely connected to the properties of individual lipid components and their interplay. The TFLL contains unique ultra-long polar lipid species such as O-acyl-ω-hydroxy fatty acids, type I-St diesters and type II diesters, which are considered important for its proper function. Herein, we have synthesized model compounds from these categories and studied their biophysical and surface rheological properties at the aqueous interface. Altogether, we provide insights on the distinct biophysical profiles of these lipid classes and discuss how their interplay may affect the structure and function of the TFLL.

Exploring Alkyl-O-Alkyl Ether Structures in Softwood Milled Wood Lignins.

Recent studies have suggested that there are significant amounts of various alkyl ether (Alk-O-Alk; Alk = alkyl) moieties in a spruce native lignin preparation, milled wood lignin (SMWL). However, the comprehensive NMR assignment to these moieties has not been addressed yet. This study focused on investigating different types of Alk-O-Alk structures at the α- and γ-positions of the lignin side chain in an heteronuclear single-quantum coherence (HSQC) spectrum of SMWL using experimental NMR data of lignin and synthesized model compounds. Ambiguous structural features were predicted by computer simulation of 1H and 13C NMR spectra to complement the experimental NMR data. As a result, specific regions in the HSQC spectrum were attributed to different Alk-O-Alk moieties of Alk-O-Alk/β-O-4 and Alk-O-Alk/β-β' structures. However, the differences between the specific regions were rather subtle; they were not well separated from each other and some major lignin moieties. Furthermore, SMWL contained a large variety of Alk-O-Alk moieties but in minute individual amounts, resulting in rather broad, superimposing resonances. Thus, evaluation did not allow assigning individual types of Alk-O-Alk moieties from the HSQC spectra; instead, they were quantified as total (α- and γ-linked) Alk-O-Alk based on the balance of structural units in the 13C NMR spectra. At last, potential formation mechanisms of various Alk-O-Alk ether structures in lignin biosynthesis, lignin aging, and during ball milling of wood were hypothesized and discussed.

Synthesis and photocatalytic activity of two different hydrogenase models based on DMAEMA copolymer structure

In this paper, the copolymers (3/3a, 4/4a) of styrene phosphine derivatives (1, 2) and DMAEMA(Dimethylaminoethyl methacrylate) were synthesized by free radical polymerization. On this basis, two phosphine ligand substituted hydrogenase models were further synthesized. They were 5/5a containing different proportions of PNP{N[P(C6H5)2]2} ligands and 6/6a containing different proportions of PCP{N[CH2P(C6H5)2]2} ligands. The newly synthesized model compounds have good solubility in various solvents. The intermediates and final products were characterized by NMR, GPC, EDX, XPS, FT-IR, ICP-MS and TG-DTA. The photocatalytic performances of the catalysts were studied. Under the preferred conditions, the turnover numbers were 75(5a) and 113(6a) for catalysts in an hour of illumination. Under the same conditions, the photocatalytic efficiency of the catalysts were significantly better than that of similar small molecule or supported hydrogenase models reported in other literatures. In addition, a possible photocatalytic mechanism was proposed.

Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group.

This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature, and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O-)═S) and nucleotide (5'-O-methoxyphosphorothioyl-2'-deoxyguanosine (G-P(O-)═S)). ESR investigations show that DMTP(O-)═S reacts with Cl2•- to form the σ2σ*1 adduct radical -P-S[Formula: see text]Cl, which subsequently reacts with DMTP(O-)═S to produce [-P-S[Formula: see text]S-P-]-. -P-S[Formula: see text]Cl in G-P(O-)═S undergoes hole transfer to Gua, forming the cation radical (G•+) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O-)═S forms the thiyl radical (-P-S•) by one-electron oxidation, which did not produce [-P-S[Formula: see text]S-P-]-. Gua in G-P(O-)═S is oxidized unimolecularly by the -P-S• intermediate in the sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.

A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging.

Optical imaging of microbial infections, based on the detection of targeted fluorescent probes, offers high sensitivity and resolution with a relatively simple and portable setup. As the absorbance of near-infrared (NIR) light by human tissues is minimal, using respective tracers, such as IRdye800CW, enables imaging deeper target sites in the body. Herein, we present a general strategy for the conjugation of IRdye800CW and IRdye700DX to small molecules (vancomycin and amphotericin B) to provide conjugates targeted toward bacterial and fungal infections for optical imaging and photodynamic therapy. In particular, we present how the use of coupling agents (such as HBTU or HATU) leads to high yields (over 50%) in the reactions of amines and IRDye-NHS esters and how precipitation can be used as a convenient purification strategy to remove excess of the targeting molecule after the reaction. The high selectivity of the synthesized model compound Vanco-800CW has been proven in vitro, and the development of analogous agents opens up new possibilities for diagnostic and theranostic purposes. In times of increasing microbial resistance, this research gives us access to a platform of new fluorescent tracers for the imaging of infections, enabling early diagnosis and respective treatment.

Elucidation of In Situ Ligninolysis Mechanisms of the Selective White-Rot Fungus Ceriporiopsis subvermispora

Lignin degradation by white-rot fungi is an essential step in terrestrial carbon cycling and has great potential for biotechnological applications. Selective white-rot fungi have been recognized for their ability to effectively delignify lignocellulose, but the underlying mechanisms, particularly in situ, have largely remained elusive to date. In this work, we elucidate specific degradation routes of β-O-4 aryl ethers in actual lignocellulosic biomass for the industrially relevant selective white-rot fungus Ceriporiopsis subvermispora. Multidimensional NMR and py-GC-MS analyses together with enzymatically synthesized model compounds enabled, for the first time, the identification of various diagnostic lignin cleavage products in residual wheat straw. Our results support that in situ ligninolysis by C. subvermispora is initiated by single-electron transfer, which then cascades into the cleavage of Cα-Cβ, Cβ-O, and O-4-aryl bonds of β-O-4 aryl ethers. The high abundance of 1-(benzyl)-2,3-dihydroxypropan-1-ones indicated that β-O-|4 cleavage is a more important pathway than previously considered. Our approach highlights key diagnostic substructures for providing mechanistic insight into fungal ligninolysis.

Solid phase synthesis of new thiazolidinedione-pyrimidine conjugates and their antibacterial properties

The polymer-supported synthetic protocol for preparation of thiazolidinedione-pyrimidine hybrids was developed and applied for rapid and effective synthesis of a library of variously substituted conjugates. Reported synthetic methodology is based on easy accessible building blocks and very simple chemical operations enabling effective development of potent experimental therapeutics of this type via a combinatorial manner. Synthesized model compounds were tested for their antitubercular activity against Mycobacterium tuberculosis H37Rv, antimicrobial activity against several Gram-positive and Gram-negative strains such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis and two fungal strains (Candida albicans and Aspergillus niger). Slight activity was found for some of them.

Interactions of 15N-Sulfadiazine and Soil Components As Evidenced by 15N-CPMAS NMR

The extensive use of sulfonamides (SNs) in animal husbandry has led to an unintentional widespread occurrence in several environmental compartments. The implementation of regulations and management recommendations to reduce the potential risk of development of antibiotic resistances necessitates detailed knowledge on their fate in soil. We present results from two independent incubation studies of 15N-labeled sulfadiazines (SDZ) which focused on identifying binding types in bound residues. In the first study 15N-amino labeled SDZ was incubated with two previously isolated humic acids in the presence and absence of Trametes versicolor laccase, while in the second study 15N-double-labeled SDZ was incubated with a typical agricultural Luvisol and the humic acid fraction isolated after sequential extraction of the soil. The freeze-dried humic acid fractions of both studies were then analyzed by 15N-CPMAS NMR and compared with the 15N-spectra of synthesized model compounds. In both studies amide bonds and Michael adducts were identified, while formation of imine bonds could be excluded. In the humic acid study, where less harsh extraction methods were applied, possible formation of H-bridging and sequestration were additionally detected.

Regioisomeric Preference in Ring-Opening Polymerization of 3',5'-Cyclic Phosphoesters of Functional Thymidine DNA Analogues.

Regioregularity is a crucial property in the synthesis of DNA analogues, as natural DNA is synthesized exclusively in the 5' to 3' direction. We have focused our attention on the determination of the regioisomeric distribution of poly(3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate)s obtained from the ring-opening polymerization of (R)-3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate. The regioisomeric preference was investigated by comparison to synthesized model compounds of 3',3'-, 3',5'-, and 5',5'-linkages, where the model 3'-phosphoester linkages were to the secondary alcohol of 3-hydroxytetrahydrofuran and the model 5'-linkages derived from coupling to the primary alcohol of tetrahydrofurfuryl alcohol. From the 31P resonance frequency assignments of those small molecule model compounds, 31P NMR spectra revealed the major connectivity in the polymer backbone to be 3',5'-linkages, with ≤30% of other isomeric forms. Model reactions employing a series of alcohol initiators imparting various degrees of steric hindrance, to mimic the increased steric hindrance of the propagating alcohol relative to the initiator, were then conducted to afford the corresponding ring-opened unimer adducts and to gain understanding of the regioselectivity during the ring-opening polymerization. 1H-31P heteronuclear multiple-bond correlation spectroscopy showed ethanol and 4-methoxybenzyl alcohol initiation to yield only the P-O5' bond cleavage product, whereas attack by isopropyl alcohol upon (R)-3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate afforded both P-O3' and P-O5' bond cleavage products, supporting our hypothesis that the increased steric hindrance of the propagating species dictates the regioselectivity of the P-O bond cleavage. Further model reactions suggested that the P-O5' bond cleavage products can be detected upon the formation of dimers during the ring-opening polymerization. Overall, this work provides a fundamental understanding of the polymerization behavior of six-membered cyclic phosphoesters and broadens the scope of DNA analogues from the ring-opening polymerization of 3',5'-cyclic phosphoesters.

Li+-Induced fluorescent metallogel: a case of ESIPT-CHEF and ICT phenomenon

A fluorescent metallogel (1% w/v) has been synthesized from non-fluorescent ingredients viz. the smallest possible low molecular weight aromatic symmetrical ligand H2SA (1) and LiOH in a chloroform and methanol mixture. The chelation of Li+ is not only responsible for the inhibition of excited state intramolecular proton transfer (ESIPT) or the origin of fluorescence through chelation enhanced fluorescence (CHEF) in 1, but also for aggregation leading to gelation. The metallogel obtained from 1/Li+ reveals a fibrous morphology while 1 with other, bigger size, alkali metal ions like Na+/K+/Cs+ demonstrates the growth of crystals with different shapes. The effect of the size of the alkali metal ion over gel formation is well explored by FTIR, UV-vis, fluorescence, average lifetime measurements, SEM and PXRD. The metallogel shows multi-stimuli responsive behaviour towards thermal and mechanical stress as well as reswelling properties. The regioisomer H2PBA (2) also shows emission upon treatment with LiOH due to the presence of intramolecular charge transfer (ICT), this is well established by various experiments. The mechanism of gel formation is well established by FTIR, 1H NMR, UV-vis, fluorescence, lifetime measurements, SEM and single crystal and powder XRD instrumental techniques. The involvement of various phenomena in gel formation has been further supported by other synthesized model compounds viz. H2MBA (3), PMO (4), H2SEA (5) and H2SPA (6). True gel phase material is proved by detailed rheological experiments.

Toblerols: Cyclopropanol-Containing Polyketide Modulators of Antibiosis in Methylobacteria.

Trans-AT polyketide synthases (PKSs) are a family of biosynthetically versatile modular type I PKSs that generate bioactive polyketides of impressive structural diversity. In this study, we detected, in the genome of several bacteria a cryptic, architecturally unusual trans-AT PKS gene cluster which eluded automated PKS prediction. Genomic mining of one of these strains, the model methylotroph Methylobacterium extorquens AM1, revealed unique epoxide- and cyclopropanol-containing polyketides named toblerols. Relative and absolute stereochemistry were determined by NMR experiments, chemical derivatization, and the comparison of CD data between the derivatized natural product and a synthesized model compound. Biosynthetic data suggest that the cyclopropanol moiety is generated by carbon-carbon shortening of a more extended precursor. Surprisingly, a knock-out strain impaired in polyketide production showed strong inhibitory activity against other methylobacteria in contrast to the wild-type producer. The activity was inhibited by complementation with toblerols, thus suggesting that these compounds modulate an as-yet unknown methylobacterial antibiotic.

Toblerols: Cyclopropanol‐Containing Polyketide Modulators of Antibiosis in Methylobacteria

AbstractTrans‐AT polyketide synthases (PKSs) are a family of biosynthetically versatile modular type I PKSs that generate bioactive polyketides of impressive structural diversity. In this study, we detected, in the genome of several bacteria a cryptic, architecturally unusual trans‐AT PKS gene cluster which eluded automated PKS prediction. Genomic mining of one of these strains, the model methylotroph Methylobacterium extorquens AM1, revealed unique epoxide‐ and cyclopropanol‐containing polyketides named toblerols. Relative and absolute stereochemistry were determined by NMR experiments, chemical derivatization, and the comparison of CD data between the derivatized natural product and a synthesized model compound. Biosynthetic data suggest that the cyclopropanol moiety is generated by carbon–carbon shortening of a more extended precursor. Surprisingly, a knock‐out strain impaired in polyketide production showed strong inhibitory activity against other methylobacteria in contrast to the wild‐type producer. The activity was inhibited by complementation with toblerols, thus suggesting that these compounds modulate an as‐yet unknown methylobacterial antibiotic.

Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin.

Structure-activity relationship studies of maitotoxin (MTX), a marine natural product produced by an epiphytic dinoflagellate, were conducted using chemically synthesized model compounds corresponding to the partial structures of MTX. Both enantiomers of the LMNO ring system were synthesized via aldol reaction of the LM ring aldehyde and the NO ring ketone. These fragments were derived from a common cis-fused pyranopyran intermediate prepared through a sequence involving Nozaki-Hiyama-Kishi reaction, intramolecular oxa-Michael addition, and Pummerer rearrangement. The NOPQR(S) ring system, in which the original seven-membered S ring was substituted with a six-membered ring, was also synthesized through the coupling of the QR(S) ring alkyne and the NO ring aldehyde and the construction of the P ring via 1,4-reduction, dehydration, and hydroboration. The inhibitory activities of the synthetic specimens against MTX-induced Ca2+ influx were evaluated. The LMNO ring system and its enantiomer induced 36 and 18% inhibition, respectively, at 300 μM, whereas the NOPQR(S) ring system elicited no inhibitory activity.

Radical synthesis of tetrameric lignin model compound

Abstract The lack of suitable lignin model compound limits the understanding of the characteristics of lignin, and hence hinders the efficient utilization of this kind of bioresource. A tetramer phenolic lignin model compound composed of 5-5, α - O -4 and β -5 linkages was prepared by a two-step of free radical reaction with hydrogen peroxide/horseradish peroxidase and S 2 O 8 2− /Fe 2+ as the initiator. Compared with enzymatic process, this synthetic process gives a higher yield of 33.8% within a shorter time. HRMS and 13 C NMR spectroscopy show that synthesized model compound contains phenylpropane structure linked by 5-5, α - O -4 and β -5 bonds, which can mimic some chemical characteristics of lignin.

Green Emission in Ladder‐Type Quarterphenyl: Beyond the Fluorenone‐Defect

In polyfluorenes it is generally accepted that (photo)degradation leads to fluorenone type defects that accept the excitation energy and emit green‐to‐yellow light with rather low efficiency. Although initial spectroscopic studies suggest the same to hold true for ladder‐type poly(para‐phenylene)s (LPPPs), kinetic studies of the degradation process are not compatible with the established mechanism. In general, the observed green emission can be caused by the introduction of carbonyl groups; however, only if associated with an additional disruption of the backbone rigidity and hence planarity of the entire π‐system. This is clearly shown by comparison with synthesized model compounds, which are bearing the fluorenone motif yet possess very different optical properties as compared to the defects, which are actually formed. Degradation can be caused by solvent specific, yet substrate nonspecific aromatic formylation but mainly originates from reaction with in‐situ generated singlet oxygen, both in solution as well as in thin films. Time‐dependent photoluminescence measurements on thin films show that green emission is enhanced by energy transfer from intact molecules to defect centers.

Water-Mediated Interactions Influence the Binding of Thapsigargin to Sarco/Endoplasmic Reticulum Calcium Adenosinetriphosphatase

A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors.

Mixed‐valence class I transition and electrochemistry of bis(triphenylamine)‐based aramids containing isolated ether‐linkage

AbstractA series of solution‐processable electrochromic (EC) aromatic polyamides with bis(triphenylamine)ether (TPAO) units in the backbone were prepared by the phosphorylation polyamidation from a newly synthesized diamine monomer, bis(N‐4‐aminophenyl‐N‐4‐methoxyphenyl‐4‐aminophenyl)ether, and various dicarboxylic acids. These polymers were highly soluble in many organic solvents and showed useful levels of thermal stability associated with high glass‐transition temperatures and high char yields (higher than 50 at 800 °C in nitrogen). The polymer films showed reversible electrochemical oxidation and electrochromism with high contrast ratio in the visible range, which also exhibited moderate coloration efficiency (CE), low switching time, and good stability. Especially, the polyamides with two electroactive nitrogen centers only showed one‐stage oxidative coloring (no intervalence charge‐transfer [IV‐CT] band was detected), implying the two electrons are simultaneously removed from the TPAO units on account of the ether‐linkage definitely isolated the two redox centers. The mixed‐valence (MV) Class I/II/III transition and electrochemistry of the synthesized model compounds were investigated for the bridged triarylamine system with various NN distances and intramolecular electron transfer (ET) capability. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Free Radical Oxidation of Polyunsaturated Lipids: New Mechanistic Insights and the Development of Peroxyl Radical Clocks

The peroxidation of lipids in biological membranes has been implicated in both the onset and development of most degenerative diseases. The primary products of this autoxidation process are usually lipid hydroperoxides. They form as a consequence of a free radical chain reaction: lipid peroxyl radicals propagate the chain by rate-limiting H-atom abstraction from another lipid. Studies of the mechanism of lipid peroxidation are a specific part of a wider effort to understand the more general phenomenon of hydrocarbon autoxidation, which dates back some 70 years. However, the autoxidation of lipids is generally much more complicated than that of other hydrocarbons because of additional reaction pathways afforded by a variety of uniquely positioned unsaturated bonds. Indeed, polyunsaturation is an important aspect of many of the most relevant of physiological lipids, such as linoleate and arachidonate. In this Account, we present our current understanding of the mechanism of unsaturated lipid peroxidation, effectively updating our Account on the same topic published 25 years ago. Our more recent work has, in large part, been stimulated by the discovery of the nonconjugated linoleate hydroperoxide as a product under certain autoxidation conditions. The identification of this long-elusive bis-allylic hydroperoxide prompted our kinetic characterization of the reaction leading to its formation. The product distributions obtained from autoxidations of newly synthesized model compounds, which vary in either the substitution of the bis-allylic moiety or the configuration of the double bonds, have provided key insights into the overall mechanism. These insights have in turn been reinforced by the results of theoretical calculations. The picture that emerges is one wherein the delocalized carbon-centered radicals, which arise as intermediates in these reactions, first associate with dioxygen to form pre-reaction complexes. These complexes then collapse through transition state structures that maximize the orbital interactions between the delocalized radical SOMO and dioxygen. The energies of these transition states are influenced by steric effects; thus, there are distinct changes in product distribution in the autoxidation of dienes having different substitution patterns. The radical-dioxygen complexes are also intermediates in the isomerization of allylperoxyl and pentadienylperoxyls, helping explain the high regio- and stereochemical fidelity of these processes. We have taken advantage of the rapid fragmentation of nonconjugated peroxyl radicals to develop a powerful peroxyl radical clock methodology, which can be used to determine rate constants for reactions of peroxyl radicals with molecules having rate constants ranging from 1 to 10(7) M(-1) s(-1). We can make use of this methodology to address various questions, both fundamental and applied, relating to lipid peroxidation and its inhibition by radical-trapping antioxidants.