Synthesis,Characterization and Photocleavage of Bis-decyl Pteroic Acid: A Folate Derivative with Affinity to Biomembranes†

Here, we provide mechanistic insight to the photocleavage of a compound in the folate family, namely pteroic acid. A bis-decyl chain derivative of pteroic acid was synthesized, structurally characterized and photochemically investigated. We showed that, like folic acid, pteroic acid and the decylated derivative undergo a photocleavage reaction in the presence of H₂O, while no reaction was observed in methanol solution. Furthermore, density functional theory calculations were carried out to predict relative stabilities of hypothetical mono-, bis- and tris-decylated pteroic acid derivatives to help rationalize the regioselectivity of the bis-decyl pteroic acid product. Additionally, the lipophilicity of the bis-decyl pteroic acid appears to confer a hydrophobic property enabling an interaction with biomembranes.     

Oxidation of 2'-deoxyguanosine 5'-monophosphate photoinduced by pterin: type I versus type II mechanism

UV-A radiation (320-400 nm) induces damage to the DNA molecule and its components through different photosensitized reactions. Among these processes, photosensitized oxidations may occur through electron transfer or hydrogen abstraction (type I) and/or the production of singlet molecular oxygen ((1)O2) (type II). Pterins, heterocyclic compounds widespread in biological systems, participate in relevant biological processes and are able to act as photosensitizers. We have investigated the photosensitized oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP) by pterin (PT) in aqueous solution under UV-A irrradiation. Kinetic analysis was employed to evaluate the participation of both types of mechanism under different pH conditions. The rate constant of (1)O2 total quenching (k(t)) by dGMP was determined by steady-state analysis of the (1)O2 NIR luminescence, whereas the rate constant of the chemical reaction between (1)O2 and dGMP (k(r)) was evaluated from kinetic analysis of concentration profiles obtained by HPLC. The results show that the oxidation of dGMP photosensitized by PT occurs through two competing mechanisms that contribute in different proportions depending on the pH. The dominant mechanism in alkaline media involves the reaction of dGMP with (1)O2 produced by energy transfer from the PT triplet state to molecular oxygen (type II). In contrast, under acidic pH conditions, where PT and the guanine moiety of dGMP are not ionized, the main pathway for dGMP oxidation involves an initial electron transfer between dGMP and the PT triplet state (type I mechanism). The biological implications of the results obtained are also discussed.     

Second-order advantage from kinetic-spectroscopic data matrices in the presence of extreme spectral overlapping A multivariate curve resolution--alternating least-squares approach

Multivariate curve resolution coupled to alternating least-squares (MCR-ALS) has been employed to model kinetic-spectroscopic second-order data, with focus on the achievement of the important second-order advantage, under conditions of extreme spectral overlapping among sample components. A series of simulated examples shows that MCR-ALS can conveniently handle the studied analytical problem unlike other second-order multivariate calibration algorithms, provided matrix augmentation is implemented in the spectral mode instead of in the usual kinetic mode. The approach has also been applied to three experimental examples, which involve the determination of: (1) the antiparkinsonian carbidopa (analyte) in the presence of levodopa as a potential interferent, both reacting with cerium (IV) to produce the fluorescent species cerium (III) with different kinetics; (2) Fe(II) (analyte) in the presence of the interferent Zn(II), both catalyzing the oxidation of methyl orange with potassium bromate; and (3) tartrazine (analyte) in the presence of the interferent brilliant blue, both oxidized with potassium bromate, with the interferent leading to a product with an absorption spectrum very similar to tartrazine. The results indicate good analytical performance towards the analytes, despite the intense spectral overlapping and the presence of unexpected constituents in the test samples.     

Development of Polar Order in the Liquid Crystal Phases of a 4‐Cyanoresorcinol‐Based Bent‐Core Mesogen with Fluorinated Azobenzene Wings

A bent‐core mesogen consisting of a 4‐cyanoresorcinol unit as the central core and laterally fluorinated azobenzene wings forms four different smectic LC phase structures in the sequence SmA–SmC_s–SmC_sP_AR–M, all involving polar SmC_sP_S domains with growing coherence length of tilt and polar order on decreasing temperature. The SmA phase is a cluster‐type de Vries phase with randomized tilt and polar direction; in the paraelectric SmC_s phase the tilt becomes uniform, although polar order is still short‐range. Increasing polar correlation leads to a new tilted and randomized polar smectic phase with antipolar correlation between the domains (SmC_sP_AR) which then transforms into a viscous polar mesophase M. As another interesting feature, spontaneous symmetry breaking by formation of a conglomerate of chiral domains is observed in the non‐polar paraelectric SmC_s phase.     

On the Spectral Gap of a Quantum Graph

We consider the problem of finding universal bounds of “isoperimetric” or “isodiametric” type on the spectral gap of the Laplacian on a metric graph with natural boundary conditions at the vertices, in terms of various analytical and combinatorial properties of the graph: its total length, diameter, number of vertices and number of edges. We investigate which combinations of parameters are necessary to obtain non-trivial upper and lower bounds and obtain a number of sharp estimates in terms of these parameters. We also show that, in contrast to the Laplacian matrix on a combinatorial graph, no bound depending only on the diameter is possible. As a special case of our results on metric graphs, we deduce estimates for the normalised Laplacian matrix on combinatorial graphs which, surprisingly, are sometimes sharper than the ones obtained by purely combinatorial methods in the graph theoretical literature.     

Simultaneous analysis of polar and non-polar components of cell membrane phospholipids by GC-MS

A rapid and selective GC-MS method was optimised for the simultaneous analysis of fatty acids, phosphoethanolamine, phosphoglycerol and phosphoserine, which comprise the polar headgroups of phospholipids. Enzymatic hydrolysis was used for sample preparation to selectively release fatty acids and prevent cleavage of the phosphoester bonds of the polar headgroups. A two-step consecutive derivatisation of the fatty acids and polar headgroups was applied to enable the simultaneous analysis of the selected analytes. The method was tested on samples of cell membrane phospholipids of Bacillus subtilis, a microbe with a broad spectrum of fatty acids. This approach can accelerate and simplify biotechnological research and quality control. The experimental conditions were optimised using a chemometric approach denoted as experimental design.     

Variation of Loewner Chains,Extreme and Support Points in the Class $$S^0$$ in Higher Dimensions

We introduce a family of natural normalized Loewner chains in the unit ball, which we call “geräumig”—spacious—which allow us to construct, by means of suitable variations, other normalized Loewner chains which coincide with the given ones from a certain time on. We apply our construction to the study of support points, extreme points, and time-\(\log M\)-reachable mappings in the class \(S^0\) of mappings admitting parametric representation.     

Mass spectrometric approaches for elucidation of antigenantibody recognition structures in molecular immunology

Mass spectrometric approaches have recently gained increasing access to molecular immunology and several methods have been developed that enable detailed chemical structure identification of antigen-antibody interactions. Selective proteolytic digestion and MS-peptide mapping (epitope excision) has been successfully employed for epitope identification of protein antigens. In addition, "affinity proteomics" using partial epitope excision has been developed as an approach with unprecedented selectivity for direct protein identification from biological material. The potential of these methods is illustrated by the elucidation of a beta-amyloid plaque-specific epitope recognized by therapeutic antibodies from transgenic mouse models of Alzheimer's disease. Using an immobilized antigen and antibody-proteolytic digestion and analysis by high resolution Fourier transform ion cyclotron resonance mass spectrometry has lead to a new approach for the identification of antibody paratope structures (paratope-excision; "parex-prot"). In this method, high resolution MS-peptide data at the low ppm level are required for direct identification of paratopes using protein databases. Mass spectrometric epitope mapping and determination of "molecular antibody-recognition signatures" offer high potential, especially for the development of new molecular diagnostics and the evaluation of new vaccine lead structures.     

Photosensitization of 2'-deoxyadenosine-5'-monophosphate by pterin

UV-A radiation (320-400 nm) induces damages to the DNA molecule and its components through photosensitized reactions. Pterins, heterocyclic compounds widespread in biological systems, participate in relevant biological processes and are able to act as photosensitizers. We have investigated the photosensitization of 2'-deoxyadenosine-5'-monophosphate (dAMP) by pterin (PT) in aqueous solution under UV-A radiation. The effect of pH was evaluated, the participation of oxygen was investigated and the products analyzed. Kinetic studies revealed that the reactivity of dAMP towards singlet oxygen (1O2) is very low and that this reactive oxygen species does not participate in the mechanism of photosensitization, although it is produced by PT upon UV-A excitation. In contrast, analysis of irradiated solutions by means of electrospray ionization mass spectrometry strongly suggested that 8-oxo-7,8-dihydro-2'-deoxyadenosine-5'-monophosphate (8-oxo-dAMP) was produced, indicating that the photosensitized oxidation takes place via a type I mechanism (electron transfer).     

Inclusion complexes of cyclodextrins with biradicals linked by a polyether chain--an EPR study

Complexation of beta-cyclodextrin with flexible nitroxide biradicals linked by a polyethylene glycol chain was monitored by EPR spectroscopy. The EPR spectra of the uncomplexed biradicals show an exchange interaction due to the flexibility of the polyethylene glycol chain. Complexation with cyclodextrin leads to the disappearance of the exchange interaction in the EPR spectra. The complexation can be reversed by the addition of competing guests (e.g., adamantane derivatives). At high concentration, the inclusion complexes precipitate, and differential scanning calorimetry (DSC) of the precipitates proved the formation of complexes. Elemental analysis data revealed that the complexes contain several cyclodextrin units per biradical but that the composition was not stoichiometric.