Amine Protons Research Articles

Synthesis, and molecular sensing behavior of fac-[Re(CO)3(κ2-N,N-dpksc)Cl], dpksc = di-2-pyridyl ketone semicarbazone

When [Re(CO)5Cl] was allowed to react with di-2-pyridyl ketone semicarbazone hydrochloride (dpksc.HCl) in refluxing toluene, fac-[Re(CO)3(κ2-N,N-dpksc)Cl] was isolated. The identity of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] was elucidated from the results of its elemental analysis and confirmed using a number of spectroscopic measurements. Spectroscopic measurements done on non-aqueous solvents divulged sensitivity of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] to changes in its surroundings. 1H NMR studies revealed significant solvent dependence as manifested by the chemical shift variations; the exchange of the amine protons with solvent deuterium in CDCl3 and d6-acetone; the temperature dependence of the chemical shifts of the amine and amide protons and insignificant temperature dependence of the aromatic proton. The electronic absorption spectra of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] measured on non-aqueous solvents disclosed two high energy intra-ligand charge transfer (ILCT) transitions. Optical measurements performed on protophilic solutions of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] in the presence of bases and acids showed the appearance and disappearance of a low energy ILCT electronic transitions and established reversible inter-conversion between fac-[Re(CO)3(κ2-N,N-dpksc)Cl] and its conjugate base, fac-[Re(CO)3(κ2-N,N-dpksc-H)Cl]−. Thermo-optical measurements done on protophilic solutions of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] disclosed the absence of thermal acid–base inter-conversion between fac-[Re(CO)3(κ2-N,N-dpksc)Cl] and fac-[Re(CO)3(κ2-N,N-dpksc-H)Cl]− and established reversible electronic transfer between the high energy electronic transitions of fac-[Re(CO)3(κ2-N,N-dpksc)Cl]. Optosensing measurements done on protophilic solutions of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] showed acids and bases in concentrations as low as 1.00×10−10 M can be detected and determined using protophilic solutions of of fac-[Re(CO)3(κ2-N,N-dpksc)Cl]. Electrochemical measurements on dmf solutions of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] showed irreversible electrochemical redox process and electrochemically generated product waves pointing to the instability of fac-[Re(CO)3(κ2-N,N-dpksc)Cl] to redox transformations.

Detection of rapidly exchanging compounds using on‐resonance frequency‐labeled exchange (FLEX) transfer

Frequency-labeled exchange transfer is a promising MRI technique for labeling and detecting exchanging protons of low-concentration solutes through the water signal. Early frequency-labeled exchange studies have used off-resonance excitation-based labeling schemes that are well suited to study rapidly exchanging protons or molecules far from the water resonance (e.g., water in paramagnetic contrast agents) or slowly exchanging protons close to the water resonance (e.g., some amide protons). However, off-resonance labeling is not efficient for rapidly exchanging protons close to water. Here, we show that a new frequency-labeled exchange labeling scheme with excitation pulses applied on the water resonance gives much higher exchange contrast for rapidly exchanging protons resonating close to the water resonance frequency. This labeling scheme is particularly suited for studying rapidly exchanging hydroxyl, amine, and imino protons in diamagnetic chemical exchange saturation transfer agents.

Evaluating the use of a continuous approximation for model-based quantification of pulsed chemical exchange saturation transfer (CEST)

Many potential clinical applications of chemical exchange saturation transfer (CEST) have been studied in recent years. However, due to various limitations such as specific absorption rate guidelines and scanner hardware constraints, most of the proposed applications have yet to be translated into routine diagnostic tools. Currently, pulsed CEST which uses multiple short pulses to perform the saturation is the only viable irradiation scheme for clinical translation. However, performing quantitative model-based analysis on pulsed CEST is time consuming because it is necessary to account for the time dependent amplitude of the saturation pulses. As a result, pulsed CEST is generally treated as continuous CEST by finding its equivalent average field or power. Nevertheless, theoretical analysis and simulations reveal that the resulting magnetization is different when the different irradiation schemes are applied. In this study, the quantification of important model parameters such as the amine proton exchange rate from a pulsed CEST experiment using quantitative model-based analyses were examined. Two model-based approaches were considered – discretized and continuous approximation to the time dependent RF irradiation pulses. The results showed that the discretized method was able to fit the experimental data substantially better than its continuous counterpart, but the smaller fitted error of the former did not translate to significantly better fit for the important model parameters. For quantification of the endogenous CEST effect, such as in amide proton transfer imaging, a model-based approach using the average power equivalent saturation can thus be used in place of the discretized approximation.

Interaction of nucleic acids with carbon nanotubes and dendrimers

Nucleic acid interaction with nanoscale objects like carbon nanotubes (CNTs) and dendrimers is of fundamental interest because of their potential application in CNT separation, gene therapy and antisense therapy. Combining nucleic acids with CNTs and dendrimers also opens the door towards controllable self-assembly to generate various supra-molecular and nano-structures with desired morphologies. The interaction between these nanoscale objects also serve as a model system for studying DNA compaction, which is a fundamental process in chromatin organization. By using fully atomistic simulations, here we report various aspects of the interactions and binding modes of DNA and small interfering RNA (siRNA) with CNTs, graphene and dendrimers. Our results give a microscopic picture and mechanism of the adsorption of single- and double-strand DNA (ssDNA and dsDNA) on CNT and graphene. The nucleic acid-CNT interaction is dominated by the dispersive van der Waals (vdW) interaction. In contrast, the complexation of DNA (both ssDNA and dsDNA) and siRNA with various generations of poly-amido-amine (PAMAM) dendrimers is governed by electrostatic interactions. Our results reveal that both the DNA and siRNA form stable complex with the PAMAM dendrimer at a physiological pH when the dendrimer is positively charged due to the protonation of the primary amines. The size and binding energy of the complex increase with increase in dendrimer generation. We also give a summary of the current status in these fields and discuss future prospects.

Deuterium kinetic isotope effects in heterotetrameric sarcosine oxidase from Corynebacterium sp. U-96: the anionic form of the substrate in the enzyme–substrate complex is a reactive species

Heterotetrameric sarcosine oxidase is a flavoprotein that catalyses the oxidative demethylation of sarcosine. It is thought that the dehydrogenated substrate is the anionic form of sarcosine. To verify this assumption, the rate of flavin-adenine dinucleotide (FAD) reduction (k(red)) was analysed using protiated and deuterated sarcosine (N-methyl-d(3)-Gly) at various pH values using stopped-flow method. By increasing the pH from 6.2 to 9.8, k(red) increased for both substrates and reached a plateau, but the pK(a) value (reflecting the ionization of the enzyme-substrate complex) was 6.8 and 7.1 for protiated and deuterated sarcosine, respectively, and the kinetic isotope effect of k(red) decreased from approximately 19 to 8, indicating deprotonation of the bound sarcosine. The k(red)/K(d) (K(d), sarcosine dissociation constant) increased with increasing pH and reached a plateau. The pK (reflecting the ionization of free enzyme or free sarcosine) was 7.0 for both substrates, suggesting deprotonation of the βLys358 residue, which has a pK(a) of 6.7, as the pK(a) of the free sarcosine amine proton was determined to be approximately 10.1. These results indicate that the amine proton of sarcosine is transferred to the unprotonated Lys residue in the enzyme-substrate complex.

Exchange rates of creatine kinase metabolites: feasibility of imaging creatine by chemical exchange saturation transfer MRI

Creatine (Cr), phosphocreatine (PCr) and adenosine-5-triphosphate (ATP) are major metabolites of the enzyme creatine kinase (CK). The exchange rate of amine protons of CK metabolites at physiological conditions has been limited. In the current study, the exchange rate and logarithmic dissociation constant (pKa) of amine protons of CK metabolites were calculated. Further, the chemical exchange saturation transfer effect (CEST) of amine protons of CK metabolites with bulk water was explored. At physiological temperature and pH, the exchange rate of amine protons in Cr was found to be 7-8 times higher than PCr and ATP. A higher exchange rate in Cr was associated with lower pKa value, suggesting faster dissociation of its amine protons compared to PCr and ATP. CEST MR imaging of these metabolites in vitro in phantoms displayed predominant CEST contrast from Cr and negligible contribution from PCr and ATP with the saturation pulse parameters used in the current study. These results provide a new method to perform high-resolution proton imaging of Cr without contamination from PCr. Potential applications of these finding are discussed.

Protonation constants and thermodynamic properties of amines for post combustion capture of CO2

The leading process for the post combustion capture (PCC) of CO2 from coal-fired power stations and hence reduction in greenhouse gases involves capture by aqueous amine solutions. Of the reactions that occur in solution, which include CO2 hydration, de-protonation of carbonic acid, amine protonation and carbamate formation, the protonation of the amine in the absorber and its subsequent de-protonation in the stripper involve the greatest enthalpy changes. In this study, protonation constants (reported as log10Kprot) of selected series of primary, secondary and tertiary alkanolamines/amines over the temperature range 288–318K are reported. Selected series studied involve primary, secondary and tertiary mono-, di- and tri-alkanolamines, secondary amines including heterocyclic species, and both –CH2OH and –CH2CH2OH substituted piperidines. van’t Hoff analyses have resulted in the standard molar enthalpies, ΔHmo, and molar entropies, ΔSmo, of protonation. Trends in ΔHmo are correlated with systematic changes in composition and structure of the selected series of amines/alkanolamines, while ΔHmo–ΔSmo plots generated linear correlations for the mono-, di-, and tri-alkanolamines, the –CH2OH and –CH2CH2OH substituted piperidines, and the alkylamines. These relationships provide a guide to the selection of an amine(s) solvent for CO2 capture, based on a greater difference in log10Kprot between the absorber and stripper temperatures.

Identification of imine or enamine drug metabolites using online hydrogen/deuterium exchange and exact mass measurements

Drug metabolites that have imine or enamine partial structures cause extra mass-to-charge (m/z) increases in online hydrogen/deuterium exchange (HDX) in addition to hydroxyl or amine protons. Online HDX and exact mass measurement were used herein to characterize this extra increase property, and to further confirm proposed metabolite structures. Metabolites of two proprietary compounds as well as two commercially available compounds were analyzed using aqueous and HDX liquid chromatography coupled with an LTQ-Orbitrap. The exact mass measurements of both the precursor ions and product ions were acquired through data-dependent acquisition and compared with theoretical values of proposed fragment ions. Analysis of exact mass measurements of metabolite product ions under both normal aqueous and HDX conditions led to the identification of the isoxazole ring opening of compound C-1, and a double-bond formation on the methylpyrrolidine ring of compound C-2 during biotransformation. In both cases, imine or enamine structures formed in the metabolites caused extra m/z increases upon HDX that contributed confirmatory information to the structure identification. The compound 3,3-diphenyl-2-ethyl-1-pyrroline also demonstrated that the methylene protons adjacent to the imine were exchanged during online HDX. The exchangeability of methylene protons adjacent to imine or enamine moieties proved to be useful to narrow down or even pinpoint the metabolism sites of parent drugs when high-resolution exact mass measurement and online HDX were used.

Sampling the Proton Transfer Reaction Coordinate in Mixed Quantum-Classical Molecular Dynamics Simulations

An umbrella sampling approach based on the vibrational energy gap is presented and examined for exploring the reaction coordinate for a proton transfer (PT) reaction. The technique exploits the fact that for a PT reaction the energy gap between the vibrational ground and excited states of the transferring proton reaches a minimum at the transition state. Umbrella sampling is used within mixed quantum-classical simulations to identify the transition state configurations and explore the reaction free energy curve and vibrationally nonadiabatic coupling. The method is illustrated by application to a model phenol-amine proton transfer reaction complex in a nanoconfined solvent. The results from this new umbrella sampling approach are consistent with those obtained from previous umbrella sampling calculations based on a collective solvent coordinate. This sampling approach further provides insight into the vibrationally nonadiabatic coupling for the proton transfer reaction and has potential for simulating vibrational spectra of PT reaction complexes in solution.

Synthesis, limitations, and thermal properties of energetically-substituted, protonated imidazolium picrate and nitrate salts and further comparison with their methylated analogs

The possibility of forming simple energetic ionic liquids via the straightforward protonation of heterocyclic amines with nitric or picric acid was explored with 1-alkylimidazoles, 1-alkyl-2-methylimidazoles, and nitro, dinitro, and dicyano-substituted derivatives. The melting points of most of the prepared salts were lower than expected and of the 30 compounds prepared, more than half were found to melt below 100 °C. Limitations in the approach were found as a result of the use of energetic electron withdrawing substituents, such as nitro or cyano, which results in a reduction in nucleophilicity of the heterocycle and an inability to form salts with the acids studied. Interesting thermal behavior was observed with several of the new salts including supercooling and crystallization on heating. Comparison of the simple protonated imidazolium nitrate and picrate salts with their methylated analogs indicated that the protonated ionic liquids do not differ substantially in their melting points from the methylated analogs. However, the thermal stabilities of protonated imidazolium salts are much lower than their alkylated derivatives. Nitrate salts with alkylated cations tend to be more thermally stable than the corresponding picrate salts, but with protonated cations, the picrate salts tend to be approximately 70–80 °C more stable than the nitrate salts. Moreover, accelerating rate calorimetry (ARC) revealed that alkylated salts decompose much less exothermically (in some cases endothermically) than the protonated analogs, and that among all the analyzed salts, the most energetic materials found were protonated 1-methylimidazolium nitrate and 1,2-dimethylimidazolium picrate.

Reversible Swelling of Chitosan and Quaternary Ammonium Modified Chitosan Brush Layers: Effect of pH and Counter Anion Size and Functionality.

This study investigates the swelling of grafted polycationic brushes as a function of pH and anion type. The brushes are chitosan (CH) and chitosans with 27% and 51% degree of substitution (DS) of quaternary ammonium salt, denoted as CH-Q(25) and CH-Q(50), respectively. The water content and swelling behaviors are monitored using in situ quartz-crystal microbalance with dissipation (QCM-D). The pH varies from ~3.5 to 8.5, and the counter anion types include chloride, acetate, and citrate. At fixed pH, the water content and brush swelling increase as the DS increases. Whereas the CH-Q(50) brush layer shows symmetric swelling with a minimum near pH = 4.5, the swelling of CH and CH-Q(25) is relatively constant as pH decreases from 8.2 to 5.5, and then begins to increase near pH 4. These studies indicate that the symmetric swelling of CH-Q(50) is likely attributed to increasing protonation of primary amines for pH values below pH 6.5 and the quaternary ammonium salts above pH 6.5. At pH 4, the swelling of the CH brush increases upon exchanging the smaller chloridewith a bulkier acetate anion, which is less effective at screening intra/inter molecular repulsion. In contrast, upon exchanging the acetate with trifunctional citrate, CH and CH-Q(25) brushes collapse by 53 and 42%, respectively, because the citrate forms ionic cross-links. To test antibacterial properties, silicon oxide, CH and CH-Q(50) brush layers are exposed to 10(7)-10(8) cfu/ml of S. aureus for two days at 37 °C and exposed to stepped shear stresses in 2 min intervals. Whereas an S. aureus biofilm adheres strongly to silicon oxide and CH for stresses up to 12 dyne/cm(2), biofilms on CH-Q(50) detach at a relatively low shear stress, 1.5 dyne/cm(2). Due to their high degree of swelling that can be tuned via pH, counterion size and type, chitosan and quaternary modified chitosans have potential as responsive coatings for applications including MEMS/NEMS devices and drug eluting implants.

Effect of amide moieties for hydrogelators on gelation property and heating-free pH responsive gel-sol phase transition

Two long-chain amidoamine derivatives (C13A2AOH and C17A2AOH) bearing three amide moieties were synthesized and their gelation ability and pH responsivity were compared with a similar, previously reported amidoamine derivative gelator with two amide moieties. C13A2AOH and C17A2AOH gels prepared in water and organic solvents acted as ambidextrous low molecular mass gelators. X-ray diffraction and Fourier transform infrared spectroscopy analyses revealed that C13A2AOH and C17A2AOH formed lamellar-like aggregates in the gels, where the amide moieties were in a strong intermolecular hydrogen-bonding state. The gelation ability, i.e., the molar ratio of solvent to gelator, was significantly dependent on the length of the alkyl chain and the number of amide moieties. In addition, the C13A2AOH and C17A2AOH hydrogels exhibited highly pH-responsive gel-sol transitions. The gel-sol transition for the hydrogels was induced by protonation of the ternary amine and the transition was completely reversible by regulating only the pH without heating.

Lanthanide(III) Complexes That Contain a Self‐Immolative Arm: Potential Enzyme Responsive Contrast Agents for Magnetic Resonance Imaging

Enzyme-responsive MRI-contrast agents containing a "self-immolative" benzylcarbamate moiety that links the MRI-reporter lanthanide complex to a specific enzyme substrate have been developed. The enzymatic cleavage initiates an electronic cascade reaction that leads to a structural change in the Ln(III) complex, with a concomitant response in its MRI-contrast-enhancing properties. We synthesized and investigated a series of Gd(3+) and Yb(3+) complexes, including those bearing a self-immolative arm and a sugar unit as selective substrates for β-galactosidase; we synthesized complex LnL(1), its NH(2) amine derivatives formed after enzymatic cleavage, LnL(2), and two model compounds, LnL(3) and LnL(4). All of the Gd(3+) complexes synthesized have a single inner-sphere water molecule. The relaxivity change upon enzymatic cleavage is limited (3.68 vs. 3.15 mM(-1) s(-1) for complexes GdL(1) and GdL(2), respectively; 37 °C, 60 MHz), which prevents application of this system as an enzyme-responsive T(1) relaxation agent. Variable-temperature (17)O NMR spectroscopy and (1)H NMRD (nuclear magnetic relaxation dispersion) analysis were used to assess the parameters that determine proton relaxivity for the Gd(3+) complexes, including the water-exchange rate (k(ex)(298), varies in the range 1.5-3.9×10(6) s(-1)). Following the enzymatic reaction, the chelates contain an exocyclic amine that is not protonated at physiological pH, as deduced from pH-potentiometric measurements (log K(H)=5.12(±0.01) and 5.99(±0.01) for GdL(2) and GdL(3), respectively). The Yb(3+) analogues show a PARACEST effect after enzymatic cleavage that can be exploited for the specific detection of enzymatic activity. The proton-exchange rates were determined at various pH values for the amine derivatives by using the dependency of the CEST effect on concentration, saturation time, and saturation power. A concentration-independent analysis of the saturation-power-dependency data was also applied. All these different methods showed that the exchange rate of the amine protons of the Yb(III) complexes decreases with increasing pH value (for YbL(3), k(ex)=1300 s(-1) at pH 8.4 vs. 6000 s(-1) at pH 6.4), thereby resulting in a diminution of the observed CEST effect.

Heteroepitaxial Streptavidin Nanocrystals Reveal Critical Role of Proton “Fingers” and Subsurface Atoms in Determining Adsorbed Protein Orientation

Characterization of noncovalent interactions between nanometer-sized structures, such as proteins, and solid surfaces is a subject of intense interest of late owing to the rapid development of numerous solid materials for medical and technological applications. Yet the rational design of these surfaces to promote the adsorption of specific nanoscale complexes is hindered by a lack of an understanding of the noncovalent interactions between nanostructures and solid surfaces. Here we take advantage of the unexpected observation of two-dimensional nanocrystals of streptavidin on muscovite mica to provide details of the streptavidin-mica interface. Analysis of atomic force microscopic images together with structural modeling identifies six positively charged residues whose terminal amine locations match the positions of the single atom-sized anionic cavities in the basal mica surface to within 1 Å. Moreover, we find that the streptavidin crystallites are oriented only along a single direction on this surface and not in either of three different directions as they must be if the protein interacted solely with the 3-fold symmetric basal surface atoms. Hence, this broken symmetry indicates that the terminal amine protons must also interact directly with the subsurface hydroxide atoms that line the bottom of these anionic cavities and generate only a single axis of symmetry. Thus, in total, these results reveal that subsurface atoms can have a significant influence on protein adsorption and orientation and identify the insertion of proton "fingers" as a means by which proteins may generally interact with solid surfaces.

Synthesis and characterization of polycation block copolymer Poly( l-lysine)- b-poly[N-(N′,N′-diisopropyl-aminoethyl)aspartamide] as potential pH responsive gene delivery system

A series of Poly( l-lysine) m- b-poly[N-(N′,N′-diisopropylaminoethyl) aspartamide] n copolymers, abbreviated as PLL m- b-P[Asp(DIP)] n were designed and synthesized via ring-opening polymerization(ROP), click chemistry, aminolysis and hydrolysis. Using 1H NMR, FT-IR and GPC, the structures and compositions of these copolymers have been verified. Through feed ratio control, block copolymer PLL m- b-P[Asp(DIP)] n with different PLL and PAsp(DIP) block lengths were obtained, which can be modified to adjust the pH responsiveness and the self-assembling behaviors of the PLL m- b-P[Asp(DIP)] n. From the results of DLS, TEM and 1H NMR, these block copolymers can form stable micelles with a partially hydrated PAsp(DIP) core and a PLL corona at pH 7.4. While as demonstrated by 1H NMR and TEM, these PLL m- b-P[Asp(DIP)] n micelle was disassembled due to further protonation of the tertiary amine in the PAsp(DIP) block at pH 5.4. These pH responsive character of the PLL m- b-P[Asp(DIP)] n micelles made them as potential pH responsive gene delivery system which may co-deliver drug and DNA simultaneously.

Hydrogen-Bond Relays in Concerted Proton–Electron Transfers

Reaction mechanisms in which electron and proton transfers are coupled are central to a huge number of processes, both natural and synthetic. Moreover, most of the new approaches to address modern energy challenges involve proton-coupled electron transfer (PCET). Recent research has focused on the possibility that the two steps are concerted, that is, concerted proton-electron transfer (CPET) reactions, rather than stepwise pathways in which proton transfer precedes (PET) or follows (EPT) electron transfer. CPET pathways have the advantage of bypassing the high-energy intermediates of stepwise pathways, although this thermodynamic benefit may have a kinetic cost. Concerted processes require short distances between the group being oxidized and the proton acceptor (and vice versa for a reduction process), which usually involves the formation of a hydrogen bond. Unlike the electron in outer-sphere electron-transfer reactions, the distance a proton may travel in a CPET is therefore rather limited. The idea has recently emerged, however, that this distance may be substantially increased via a H-bond relay located between the electron-transfer-triggered proton source and the proton acceptor. Generally speaking, the relay is a group bearing a H atom able to accept a H-bond from the moiety being oxidized and, at the same time, to form a H-bond with the proton-accepting group without going through a protonated intermediate. Although these molecules do not retain all the properties of chains of water molecules engaged in Grotthuss-type transport of a proton, the OH group in these molecules does possess a fundamental property of water molecules: namely, it is both a hydrogen-bond acceptor and a hydrogen-bond donor. Despite centuries of study, the mechanisms of proton movement in water remain active experimental and theoretical research areas, but so far with no connection to CPET reactions. In this Account, we bring together recent results concerning (i) the oxidative response of molecules containing a H-bond relay and (ii) the oxidation of phenol with water (in water) as the proton acceptor. In the first case, a nondestructive electrochemical method (cyclic voltammetry) was used to investigate the oxidation of phenol molecules containing one H-bond relay and an amine proton acceptor compared with a similar amino phenol deprived of relay. In the second, the kinetics of phenol oxidation with water (in water) as proton acceptor is contrasted with that of conventional proton acceptors (such as hydrogen phosphate and pyridine) to afford evidence of the concerted nature of Grotthuss-type proton displacement with electron transfer. First indications were provided by the same electrochemical method, whereas a more complete kinetic characterization was obtained from laser flash photolysis. Older electrochemical results concerning the reduction of superoxide ion in the presence of water are also examined. The result is a timely picture of current insight into concerted mechanisms involving electron transfer coupled with proton transport over simple H-bond relays and over H-bond networks.

Spectroscopic and electrochemical properties of di-2-pyridyl ketone thiosemicarbazone [dpktsc] in non-aqueous media

► Deprotonation of [dpktsc] is not favorable in the presence and absence of NaBH 4 . ► Facile deprotonation of [dpktsc] occurs in the presence of trace amounts of [MCl 2 ] (M = Zn, Cd or Hg). ► Reductive decomposition of [dpktsc] occurs in dmf. ► [MCl 2 (κ 3 -N,N,S-dpktsc-H] − is formed when [dpktsc] was allowed to interact with [MCl 2 ]. Spectroscopic measurements on non-aqueous solutions of [dpktsc] divulged high sensitivity of [dpktsc] to its surroundings. 1 H NMR studies performed on d 6 -dmso and d 6 -acetone solutions of [dpktsc] disclosed inter-molecular hydrogen bond between the amine proton and the solvent oxygen atom. In non-protophilic solvent (CDCl 3 ), intra-molecular hydrogen bond between the amide proton and a nitrogen atom of a pyridine ring was elucidated. Electronic absorption measurements done on non-aqueous solutions of [dpktsc] revealed two intra-ligand charge transfer transitions (ILCT) due to n → π * and π → π * of the thione followed by thione to pyridine charge transfer. In protophilic solvents, a shoulder appeared at ∼400 nm along with the ILCT transitions. Spectrophotometric titrations of [dpktsc] with NaBX 4 (X = H or F) and thermo-optical measurements in dmf disclosed that deprotonation of [dpktsc] is not favorable. When stoichiometric amounts of [MCl 2 ] (M = Zn, Cd or Hg) were added to dmf solutions of [dpktsc], facile conversion of [dpktsc] to its conjugate base [dpktsc-H] − and in situ formation of [MCl 2 (κ 3 -N,N,S-dpktsc-H] − was observed. Dmf solutions of [dpktsc] are able to detect and determine [MCl 2 ] in concentrations as low as 1.00 × 10 −12 M. Protophilic solutions (dmf) of [dpktsc] show high affinity to [ZnCl 2 ], compared to [MCl 2 ] (M = Cd or Hg). Electrochemical measurements done on dmf solutions of [dpktsc] in the presence and absence of [MCl 2 ] show reductive decomposition of [dpktsc] in the absence of [MCl 2 ] and in the presence of [MCl 2 ] electrochemical signatures consistent with the in situ formation of [MCl 2 (κ 3 -N,N,S-dpktsc-H)] − were observed.

Iron(II) PARACEST MRI Contrast Agents

The first examples of Fe(II) PARACEST magnetic resonance contrast agents are reported (PARACEST = paramagnetic chemical exchange saturation transfer). The iron(II) complexes contain a macrocyclic ligand, either 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1) or 1,4,7-tris[(5-amino-6-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane (L2). The macrocycles bind Fe(II) in aqueous solution with formation constants of log K = 13.5 and 19.2, respectively, and maintain the Fe(II) state in the presence of air. These complexes each contain six exchangeable protons for CEST which are amide protons in [Fe(L1)](2+) or amino protons in [Fe(L2)](2+). The CEST peak for the [Fe(L1)](2+) amide protons is at 69 ppm downfield of the bulk water resonance whereas the CEST peak for the [Fe(L2)](2+) amine protons is at 6 ppm downfield of bulk water. CEST imaging using a MRI scanner shows that the CEST effect can be observed in solutions containing low millimolar concentrations of complex at neutral pH, 100 mM NaCl, 20 mM buffer at 25 °C or 37 °C.

Magnetic resonance imaging of the Amine–Proton EXchange (APEX) dependent contrast

Chemical exchange between water and labile protons from amino-acids, proteins and other molecules can be exploited to provide tissue contrast with magnetic resonance imaging (MRI) techniques. Using an off-resonance Spin-Locking (SL) scheme for signal preparation is advantageous because the image contrast can be tuned to specific exchange rates by adjusting SL pulse parameters. While the amide-proton transfer (APT) contrast is obtained optimally with steady-state preparation, using a low power and long irradiation pulse, image contrast from the faster amine-water proton exchange (APEX) is optimized in the transient state with a higher power and a shorter SL pulse. Our phantom experiments show that the APEX contrast is sensitive to protein and amino acid concentration, as well as pH. In vivo 9.4-T SL MRI data of rat brains with irradiation parameters optimized to slow exchange rates have a sharp peak at 3.5 ppm and also broad peak at -2 to -5 ppm, inducing negative contrast in APT-weighted images, while the APEX image has large positive signal resulting from a weighted summation of many different amine-groups. Brain ischemia induced by cardiac arrest decreases pure APT signal from ~1.7% to ~0%, and increases the APEX signal from ~8% to ~16%. In the middle cerebral artery occlusion (MCAO) model, the APEX signal shows different spatial and temporal patterns with large inter-animal variations compared to APT and water diffusion maps. Because of the similarity between the chemical exchange saturation transfer (CEST) and SL techniques, APEX contrast can also be obtained by a CEST approach using similar irradiation parameters. APEX may provide useful information for many diseases involving a change in levels of proteins, peptides, amino-acids, or pH, and may serve as a sensitive neuroimaging biomarker.

Thermosetting resin compositions based on novolac and modified novolac

AbstractNovel formaldehyde novolac resins at various molar ratios of monomers (4,4′‐methylenedianiline/p‐nonylphenol/p‐formaldehyde) were synthesized in the presence of an acid catalyst. The obtained resins were characterized by using elemental analysis, FT IR, and 1H NMR spectroscopic methods. Subsequently, these resins may further be modified by allylation and methacrylation and may be used as cross‐linking agents for epoxy resin/bismaleimide resin formulations. The curing of epoxy and bismaleimide resins with formaldehyde resins (FR) and modified FR and the thermal decomposition behavior of cross‐linked resins were studied by differential scanning calorimetry (DSC) and thermogravimetric (TGA) techniques. DSC scans for the curing of epoxy resins with FR show a single exothermic peak, which implied only the occurrence of cure reactions between epoxy ring and amine protons, whereas the DSC scans for the epoxy resins, bismaleimide resins, and modified FR systems have two exothermic peaks. The cured products possess a good thermal stability and low water absorption. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 30: 219–233, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.20218