Sugar OH Groups Research Articles

Relaxation of the T1 excited state of 2-thiothymine, its riboside and deoxyriboside-enhanced nonradiative decay rate induced by sugar substituent

Abstract UV absorption, circular dichroism and emission spectroscopy as well as nanosecond and femtosecond transient absorption measurements were used to characterize the excited states of 2-thiothymine (2TT), its riboside (2TTR) and deoxyriboside (2TTD) in acetonitrile (ACN) solution. The lowest triplet state (T1) could be observed exclusively in the experiments. Upon excitation to higher singlet states (λexc = 266 nm), the T1 (ππ*) states of the investigated compounds were formed on an ultrafast time scale (kT ≥ 3 × 1012 s−1) with an efficiency approaching unity (ϕT = 0.9 ± 0.1). These T1 states were characterized by their intrinsic lifetimes ( τ T 0 ) and rate constants of self-quenching (kSQ), phosphorescence (kP), and nonradiative processes (∑kNR). In the series of compounds studied only 2TT exhibited a weak room-temperature phosphorescence, and the spectrum of this 2TT emission was recorded for the first time. In the absence of self quenching, nonradiative processes (NR) are the dominant (ϕNR ∼ 0.9) channel of the decay of 2TT and its nucleosides in their T1 states. Despite the chromophore being the same in all of the compounds studied, the decay dynamics of the nucleosides’ T1 states differed considerably from that of the T1 state of 2TT. The ∑kNR values determined for the derivatives containing a ribosyl (in 2TTR) or a deoxyribosyl (in 2TTD) substituent in the position α to the thiocarbonyl group were an order of magnitude larger, and as a consequence, the lifetimes ( τ T 0 ) shorter (by factor of 14 and 22 for 2TTD and 2TTR, respectively) as compared to 2TT. The reason for the enhanced rate of nonradiative decay in the nucleosides is discussed based on the results obtained from additional experiments including the determination of the T1 lifetime for the deuterated derivative of 2TTR and the intermolecular quenching of 2TT by ribose molecules. The factors which might be responsible for this substituent effect (on the nonradiative decay) such as an intramolecular or an intermolecular H bond formation involving sugar OH groups as well as a reversible H abstraction from the sugar α-substituent in the nucleosides appear to be not important.

Synthesis of Thymidine, Uridine, and 5‐Methyluridine Nucleolipids: Tools for a Tuned Lipophilization of Oligonucleotides

AbstractThree pyrimidine nucleosides, uridine (1), 5‐methyluridine (6), and 2′‐deoxythymidine (11), were converted to amphiphilic nucleolipids. Compounds 1 and 6 were lipophilized by introduction of symmetric ketal moieties with various carbon chain lengths (i.e., 5–17). Two ketal derivatives, 2b and 7a, were additionally further hydrophobized by N(3)‐farnesylation. 2′‐Deoxythymidine was alkylated at N(3) with a cetyl (=hexadecyl) residue, either directly or, after complete orthogonal protection of the sugar OH groups, by Mitsunobu reaction with hexadecan‐1‐ol. Some of the nucleolipids were subsequently converted to their 2‐cyanoethyl phosphoramidites (5′ or 3′), one of which was used for an exemplary synthesis of a lipo‐oligonucleotide. The sequence of this lipo‐oligonucleotide is an encoded manifestation of Pythagoras' law, created with a key table in which the letters of the alphabet, the numbers from 0 to 9 as well as the mostly used mathematical symbols are allocated to a ribonucleic acid triplet of the genetic code.

Spectroscopic studies of vanadium biosorption on different types of carbohydrate biomass

The biosorption potential of different types of carbohydrate biomass is investigated to evaluate their application to purify water contaminated by vanadium in environmentally relevant oxidation states (VIV and VV). Spectroscopic studies were done by electron paramagnetic resonance (EPR), vanadium nuclear magnetic resonance (51V NMR), circular dichroism (CD), and electronic absorption in the visible range (vis). Both d-galacturonic and d-glucuronic acids are major components of plant cellular wall polysaccharides. The interaction of VIV with the model ligands d-galacturonic and d-glucuronic acids showed that complexation starts at low pH values (pH 3) and that carboxylate and sugar–OH groups, as well as water molecules, are involved in the coordination. At pH > 4.5, coordination promotes the sugar–OH deprotonation and new species form with the ligand chelating the metal ion via oxygen atoms of carboxylate and of adjacent sugar–O− donors. The studies with pectin and citric acid show the ability of both compounds to partially reduce VV to VIV in solution and the EPR parameters suggest coordination of carboxylate, sugar–OH, and water molecules. The interaction of VV with biomass from different sources shows that grapefruit, orange peel, and plane tree fruit are the most suitable candidates for the biosorption of vanadium. Studies with VV and grapefruit (or the grainless stalk of corn) indicate that the reduction takes place at the “surface” of the solid. EPR studies on the interaction of VIV with different carbohydrate biomass show their ability to complex high amounts of VIV. We propose that the biosorption mechanism, when the biomass is in contact with VV species, involves sorption, reduction, and retention at the surface level of VIV coordinated by oxygen donors of the biomass. When the interaction starts with VIV, the main process just involves the uptake of the metal ion at the surface level.

Highly Effective Recognition of Carbohydrates by Phenanthroline‐Based Receptors: α‐ versus β‐Anomer Binding Preference

(1)H NMR spectroscopic titrations in competitive and non-competitive media, as well as binding studies in two-phase systems, such as phase transfer of sugars from aqueous into organic solvents and dissolution of solid carbohydrates in apolar media revealed both highly effective recognition of neutral carbohydrates and interesting binding preferences of an acyclic phenanthroline-based receptor 1. Compared to the previously described acyclic receptors, compound 1 displays significantly higher binding affinities, the rare capability to extract sugars from water into non-polar organic solutions and alpha- versus beta-anomer binding preference in the recognition of glycosides, which differs from those observed for other receptor systems. X-ray crystallographic investigations revealed the presence of water molecules in the binding pocket of 1 that are engaged in the formation of hydrogen-bonding motifs similar to those suggested by molecular modelling for the sugar OH groups in the receptor-sugar complexes. The molecular modelling calculations, synthesis, crystal structure and binding properties of 1 are described and compared with those of the previously described receptors.

Protective Role of Alginic Acid Against Metal Uptake by American Oyster (Crassostrea virginica)

Environmental Context. Trace metals are both micronutrients and toxicants, depending on concentration, and in coastal waters they bind to natural organic matter including nanoparticles. The binding type affects trace metal bioavailability to bivalves such as oysters, which ingest metals through water and food particles. Bivalves are biomonitors because of the high trace metal concentrations, especially Cu and Zn, in their tissues. Here, the polysaccharide alginic acid is shown to protect against the assimilation and bioavailability of trace metals to American oysters. Abstract. Little is known about how colloidal macromolecular organic matter (COM) modifies the bioavailability of toxic metals to aquatic organisms. In order to understand the physical and chemical properties of COM on the bioavailability of some metals to estuarine bivalves used as biomonitors, American oysters (Crassostrea virginica) were exposed to natural COMs and model acid polysaccharides (APS, alginic acid (AA), kappa carrageenan (CAR), and latex particles), and natural colloidal organic carbon (COC), tagged with either radioactive Ag, Cd, Co, Cr, Fe, Hg or Zn, or 14C-labelled sugar OH groups. Filter-feeding oysters efficiently removed latex particles 0.04 µm in diameter, with removal half-times of 2.5–5.5 h, equivalent to a filtration rate of approximately 3 L day–1 g–1. Thus, AA protects against metal uptake by oysters, which is confirmed by metal dry-weight concentration factors (DCFs) similar to, or lower than, those for 14C-labelled AA. However, metal-DCFs for CAR and COC were higher than for 14C-labelled counterparts, suggesting that in these treatments, metal uptake was enhanced over that of carbon. The 14C-labelled AA was taken up significantly more than other 14C-labelled organics, suggesting different behavior in the digestive tract. Bioavailabilty of metals bound to organic nanoparticles with different nutritional and physiological properties is not fully understood, and will require further experiments.

Comparison Of Sorption Isotherms Of Mono- and Disaccharides Relevant To Oligosaccharide Separations For Na, K, And Ca Loaded Cation Exchange Resins

Oligosaccharides (OS) are applied as a functional food and feed ingredient. OS are produced as mixtures of different types of carbohydrates, and further separation is required for most applications. An example of separation is the removal of monosaccharides in order to decrease the amount of calories and the sweet taste. The work presented here focuses on finding an optimized poly(styrene-co-divinylbenzene) cation exchange resin as the sorbent for the chromatographic removal of monosaccharides, mainly glucose, from OS. The influence of Ca2+, Na+, and K+ as the cations of Dowex 50WX4-400 was investigated by determination of isotherms under relevant industrial conditions (temperature 60°C and sugar concentrations up to 400 g/L). Both the static desorption method and the dynamic frontal analysis method were used for isotherm measurement. The two methods mentioned give slightly different isotherms, which may be attributed to the assumption of no shrinking of the resin. It was shown experimentally that K+ loaded resin has a stronger adsorption of sugars than the Na+ loaded resin. The observed isotherm order is: fructose ≈ galactose > glucose > lactose > sucrose. The lower isotherms of the disaccharides are explained by the size exclusion mechanism. The order of the monosaccharide isotherms is in line with the number of equatorial-axial oriented sugar OH groups for complexation with the cation. The observed selectivity for glucose/lactose is independent of the cations considered and about 1.3, but capacity is highest for K+ loaded resin. The selectivity for fructose over sucrose is 2.4 for Ca2+ loaded resin and is clearly higher than for Na+ and K+. Therefore, based on selectivity and capacity, the K+ ion seems the most suitable cation for separation of glucose from OS and the Ca2+ cation is the best choice for removal of fructose from OS. No mass transfer effects were included in the comparison.

Intermolecular Interactions in Dry and Rehydrated Pure and Mixed Bilayers of Phosphatidylcholine and Digalactosyldiacylglycerol: A Fourier Transform Infrared Spectroscopy Study

Glycolipids are an important part of almost all biological membranes. Their effects on membrane structure and their interactions with phospholipids, however, have not been extensively studied so far. We have investigated the phase behavior and intermolecular interactions in dry and rehydrated bilayers made from the phospholipid egg phosphatidylcholine (EPC) and the plant chloroplast glycolipid digalactosyldiacylglycerol (DGDG), or from a mixture (1:1) of these lipids, using Fourier transform infrared spectroscopy. We show that there are extensive interactions between EPC and DGDG in mixed membranes, and also between DGDG molecules in pure DGDG membranes, involving sugar OH groups and C=O, P=O, and choline moieties in dry membranes. These interactions persist to a certain degree even after rehydration. We present evidence that these interactions influence the mixing behavior in phosphatidylcholine/DGDG membranes and also the phase behavior of both EPC/DGDG and pure DGDG membranes in the dry state.

Dendritic, 1,1′-Binaphthalene-Derived Cleft-Type Receptors (Dendroclefts) for the Molecular Recognition of Pyranosides

Two series of optically active, cleft-type dendritic receptors (dendroclefts) for carbohydrate recognition were prepared by attaching Fréchet-type dendrons via ethynediyl linkers to a core consisting of one or two 1,1′-binaphthalene-2,2′-diyl phosphate moieties. Sugar substrates were expected to bind via bidentate ionic H-bonding of two OH groups to the phosphodiester core and, additionally, to undergo van der Waals and CH⋅⋅⋅π interactions with the aromatic rings of the surrounding dendritic wedges. The synthesis of the dendritic receptors G-1-(S)-1, G-2-(S)-2, and G-3-(S)-3 (Fig. 1; G-x=dendritic generation) with a single binaphthalene core started from 3,3′-diethynylated MOM-protected (MOM=methoxymethyl) 1,1′-binaphthalene-2,2′-diol (S)-13 to which the Fréchet-type dendrons of generations 1 – 3 were attached via Sonogashira cross-coupling (Scheme 3). MOM-Ether deprotection followed by phosphodiester formation and ion exchange provided the targeted receptors. By a similar route, receptor G-1-(S)-23 with dendritic wedges capped with oligoether groups was obtained (Scheme 4). In receptor G-1-(S)-26, the ethynediyl linker was omitted, and, in its synthesis, the dendritic wedges were attached to MOM-protected 3,3′-diiodo-1,1′-binaphthalene-2,2′-diol by Suzuki cross-coupling (Scheme 5). The synthesis of the dendritic receptors G-2-(S,S)-42 and G-1-(S,S)-43 with two binaphthalene moieties at the core (Fig. 3) started from diethynylated (S,S)-39 and (S,S)-33, which contain two MOM-protected 1,1′-binaphthalene-2,2′-diol moieties bridged by p-phenylene or buta-1,3-diynediyl linkers, respectively, and was completed by attachment of the dendritic wedges by Sonogashira coupling, MOM-ether deprotection, phosphodiester formation, and ion exchange (Schemes 9 and 10). By an alternative route, the C-frame of receptor G-2-(S,S)-41 was prepared by coupling the dendron to dialkynylated 1,1′-binaphthalene (S)-44, followed by oxidative Glaser-Hay coupling (Scheme 8). For control studies, the non-dendritic reference receptors (S)-4 and (S)-5 (Fig. 1) with one and (S,S)-31 and (S,S)-32 (Fig. 2) with two 1,1′-binaphthalene-2,2′-diyl phosphate moieties were also prepared. 1H-NMR Complexation studies with the dendritic receptors containing one binaphthalene core and octyl glycosides 53 – 55 in CD3CN and CDCl3 (Tables 2 – 4) revealed that ionic H-bonding between the phosphodiester core in the dendritic receptors and the sugar OH groups provides the major driving force for stoichiometric 1 : 1 host-guest association. A smaller, yet significant contribution to the binding free enthalpy was also provided by interactions between the sugar guests and the dendritic wedges. Binding selectivity was weak in all cases, and only small changes in association strength were observed as a function of dendritic generation. In studies with the dendritic receptors, which contain two binaphthalene moieties at the core, higher-order complex stoichiometries prevented the determination of quantitative binding data. As a result of unfavorable steric interactions between the dendritic wedges, these flexible receptor systems apparently avoid adopting the `syn'-conformation with convergent phosphodiester sites that is required for efficient 1 : 1 host-guest complexation.

Sugar interaction with metal ions. FT-IR study on the structure of crystalline galactaric acid and its K +, NH 4 +, Ca 2+, Ba 2+, and La 3+ complexes

The FT-IR spectra of galactaric acid and its K +, NH 4 +, Ca 2+, Ba 2+, and La 3+ salts have been recorded and interpreted. Spectroscopic evidence shows that the dimeric carboxylic groups of the free acid are dissociated upon formation of the salt, and the asymmetric and symmetric stretching vibrations of the anionic COO − group in these salts are observed at about 1600 and 1400 cm −1, respectively. The two carboxylic groups of the galactarate coordinate with Ca 2+ ions in a monodentate form. One of the carboxylic groups in the Ba 2+ salt coordinates in a monodentate state; another group interacts with three cations in a tetradentate form. In the K +, NH 4 +, and La 3+ salts, the COO − groups coordinate in a polydentate manner with the cations. By comparison of the spectra of the salts with that of the free acid, it is concluded that the hydroxyl groups of the galactarate skeleton take part in metal–oxygen interaction, and the hydrogen-bonding network is rearranged upon sugar metalation. The degree of participation of the sugar OH groups in metal–galactarate interaction is varied from the K + and NH 4 + salts to the Ca 2+, Ba 2+, and La 3+ salts.

Unusual coordination behavior of D-fructose towards dimethyltin(IV): metal-promoted deprotonation of alcoholic OH groups in aqueous solutions of low pH

To study the effect of the conformation of sugar hydroxy groups on metal complexation processes, complex formation of eight saccharides (D-fructose, L-sorbose, L-arabinose, D-arabinose, D-glucose, D-sorbitol, 2-deoxy-D-glucose and D-saccharose) with dimethyltin(IV) cations was investigated in aqueous solution by potentiometric equilibrium measurements, 13C NMR, polarimetric and Mössbauer spectroscopic methods. The experimental results proved that deprotonation of D-fructose and L-sorbose is caused by the coordination of dimethyltin(IV) in the unusual low pH interval 4–6 in contrast to the other saccharides deprotonated in analogous way at pH > 8. Increasing the pH of the solution resulted in the formation of further complexes. Stability and composition of the species was determined by potentiometric studies. 13C NMR measurements led to the assignment of the sugar OH groups participating in the processes. Mössbauer investigations in the quick-frozen solutions permitted the determination of the stereochemistry of tin(IV) in the complexes.

Complexation-induced activation of sugar OH groups. Regioselective alkylation of methyl fucopyranoside via cyclic phenylboronate in the presence of amine

Methyl fucopyranoside undergoes highly regioselective 3- O-alkylation via complexation with phenylboronic acid, followed by treatment of the resulting 3,4-boronate with iodobutane in the presence of a tertiary amine and Ag 2O. The essential step is suggested to be regioselective activation of the 3-O nucleophilic center upon amine coordination with the O-bonded boron atom.

Synthesis of N-acetylglucosaminyl asparagine-substituted puromycin analogues

As part of our project aimed to introduce specifically glycosylated amino acids into proteins, new glycosylated puromycin analogues were chemically synthesized. Introduction of a free N-acetylglucosaminyl asparaginyl side chain abolished the activity of puromycin completely, but when the sugar OH groups were rendered increasingly hydrophobic by acetylation or benzylation, up to 8% of the activity was recovered. The results of our preliminary inhibition tests suggest that the interaction of puromycin analogues and therefore also of glycosylated aminoacyl tRNA, with the ribosomal A site increases with hydrophobicity of the modifying protecting groups.

N4-(Dialkylamino)methylene Derivatives of 2′-Deoxycytidine and Arabinocytidine: Physicochemical Studies for Potential Prodrug Applications

The synthesis and physicochemical parameters of a series ofN4-(N,N-dialkyl)formamidine derivatives of 2′-deoxycytidine (dCyd,1) and arabinocytidine (ara-C,2), as prodrug prototypes, are described. The lipophilicity of the formamidine derivatives compared to that of the parent nucleosides increased 1.26- to 145-fold. The corresponding half-lives of the derivatives in aqueous solution at pH 7.4 and 37 °C ranged from 3.7 to 52 h. The analogues most stable to hydrolysis in both series (3and4) were the diisopropyl derivatives (3dand4d). The substitution effects of the sugar OH groups at the 2′- and 3′-positions on the corresponding partition coefficients gave π-values of −0.16 and −0.55, respectively. These values are significantly more positive than those generally associated with aliphatic hydroxy substituents indicating that sugar OH groups of nucleosides have a decreased tendency to associate with the aqueous phase. Thein vitrogrowth inhibitory activities of theara-C derivatives (4) against murine lymphocytic leukemia L1210 cells indicate that prodrug to drug conversion readily occurs. The results confirm our previous findings about the versatility of the formamidine modification of nucleosides bearing exocyclic amino groups. The data facilitate optimization of lipophilicities and hydrolytic stabilities and thus contribute to the design and further development of the formamidine type of prodrug derivatives.

Carbohydrate interaction with monovalent ions. The effects of Li +, Na +, K +, NH +4, Rb +, and Cs + on the solid state and solution structures of d-glucono-1,5-lactone and d-gluconic acid

The interaction of d-glucono-1,5-lactone with monovalent ions has been studied in aqueous solution at neutral pH. The d-gluconate salts of Li +, Na +, K +, NH + 4, Rb +, and Cs + were studied by 13C NMR, FTIR, and by X-ray powder diffraction. The spectroscopic evidence suggests that in aqueous solution, the alkali metal ions are hydrated, with no direct metal-sugar interaction. In the solid state, Li + is four-coordinated, binding to two different gluconate anions through the carboxylate O-1 and one of the acid anion OH groups. Na + binds to six oxygen atoms of six different acid anions. K + is six-coordinated in the anhydrous salt, binding to four oxygen atoms of the four anion carboxylate groups and to two sugar OH groups; the monohydrated shows two different types of crystals (A and B). In the A crystal, K + has eight-fold coordination, binding to six OH groups and two two H 2O, with no direct metal-carboxylate interaction, while in the B crystal, the eight coordination around K + is completed by the acid anion carboxylate and OH groups as well as a water molecule. the Rb + and K + salts are isomorphous with and rather different from the Cs + salt. The sugar intermolecular H-bonding network is rearranged upon acid ionization and salt formation.

Studies of Nucleosides and Nucleotides. LII. Purine Cyclonucleosides.(17). Synthesis and Properties of Cyclonucleosides derived from Inosine and Thioinosine

8, 2'-Anhydro-8-mercapto- 9-β-D-arabinofuranosyladenine (I), 8, 3'-anhydro-8-mercapto-9-β-D-xylofuranosyladenine (II) and 8, 5'-anhydro-8-mercapto-9-β-D-ribofuranosyladenine (III) were deaminated with barium nitrite in acetic acid to give the corresponding S-cycloinosines (IV-VI). These cyclonucleosides had characteristic properties in ultraviolet (UV), nuclear magnetic resonance (NMR), circular dichroism (CD) and mass spectra, which were as expected from those of adenosine cyclonucleosides. Compounds IV-VI were benzoylated on sugar OH groups and subjected to thiolation reaction using phosphorus pentasulfide in pyridine containing water. Deprotection either with sodium methoxide or ammonia in methanol gave 8, 2'-anhydro-6, 8-dimercapto-9-β-D-arabinofuranosylpurine (XVI), 8, 3'-anhydro-6, 8-dimercapto-9-β-D-xylofuranosylpurine (XVII) and 8, 5'-anhydro-6, 8-dimercapto-9-β-D-ribofuranosylpurine (XVIII), respectively. The structure of these cyclonucleosides was confirmed by their characteristic UV, CD, NMR and mass spectra. 6-Mercaptopurine cyclonucleosides were easily oxidized to form disulfides by air oxidation or iodine treatment.