Efficient and Inexpensive Synthesis of N-Labeled 2-Azido-1,3-dimethylimidazolinium Salts Using NaNO Instead of NaNNN.

N-Labeled azides are important probes for infrared and magnetic resonance spectroscopy and imaging. They can be synthesized by reaction of primary amines with a N-labeled diazo-transfer reagent. We present the synthesis of N-labeled 2-azido-1,3-dimethylimidazolinium salts as a N-labeled diazo-transfer reagent.

Investigation of d-Amino Acid-Based Surfactants and Nanocomposites with Gold and Silica Nanoparticles as against Multidrug-Resistant Bacteria Agents.

d-amino acid-based surfactants (d-AASs) were synthesized and their antimicrobial activity was evaluated. -α-lauroyl-d-arginine ethyl ester hydrochloride (d-LAE), d-proline dodecyl ester (d-PD), and d-alanine dodecyl ester (d-AD) were found to have antibacterial activity against both Gram-positive and -negative bacteria, but less efficacy against Gram-negative bacteria. For these reasons, combining antimicrobial agents with nanoparticles is a promising technique for improving their antibacterial properties to eliminate drug-resistant pathogens.

TfNNN: A γ-N-Labeled Diazo-Transfer Reagent for the Synthesis of β-N-Labeled Azides.

Azides are infrared (IR) probes that are important for structure and dynamics studies of proteins. However, they often display complex IR spectra owing to Fermi resonances and multiple conformers. Isotopic substitution of azides weakens the Fermi resonance, allowing more accurate IR spectral analysis.

Conversion from Heterometallic to Homometallic Metal-Organic Frameworks.

Two new heterometallic metal-organic frameworks (MOFs), LnZnTPO 1 and 2, and two homometallic MOFs, LnTPO 3 and 4 (Ln=Eu for 1 and 3, and Tb for 2 and 4; H TPO=tris(4-carboxyphenyl)phosphine oxide) were synthesized, and their structures and properties were analyzed. They were prepared by solvothermal reaction of the C -symmetric ligand H TPO with the corresponding metal ion(s) (a mixture of Ln and Zn for 1 and 2, and Ln alone for 3 and 4). Single-crystal XRD (SXRD) analysis revealed that 1 and 3 are isostructural to 2 and 4, respectively.

Ultrafast Chemical Exchange Dynamics of Hydrogen Bonds Observed via Isonitrile Infrared Sensors: Implications for Biomolecular Studies.

Local probes are indispensable to study protein structure and dynamics with site-specificity. The isonitrile functional group is a highly sensitive and H-bonding interaction-specific probe. Isonitriles exhibit large spectral shifts and transition dipole moment changes upon H-bonding while being weakly affected by solvent polarity.

Simultaneous enhancement of transition dipole strength and vibrational lifetime of an alkyne IR probe viaπ-d backbonding and vibrational decoupling.

Alkyne infrared (IR) probes 1-6 with Si and S (or Se) atoms incorporated into the C[triple bond, length as m-dash]C bond were synthesized, and the vibrational properties of their C[triple bond, length as m-dash]C stretch mode were studied using Fourier transform infrared (FTIR) and femtosecond IR pump-probe (IR PP) spectroscopies in combination with quantum chemical calculations. From FTIR studies, the transition dipole strengths (in units of 10 D) of 1-3 having the Si atom were measured to be 1.85, 3.

Cyanamide as an Infrared Reporter: Comparison of Vibrational Properties between Nitriles Bonded to N and C Atoms.

Infrared (IR) probes based on terminally blocked β-cyanamidoalanine (AlaNHCN) 1 and p-cyanamidophenylalanine (PheNHCN) 2 were synthesized, and the vibrational properties of their CN stretch modes were studied using Fourier transform infrared (FTIR) and femtosecond IR pump-probe spectroscopies in combination with quantum chemical calculations. From FTIR studies, it is found that the transition dipole strengths of the cyanamide (NHCN) group in 1 and 2 are much larger than those of the nitrile (CN) group but comparable to those of the isonitrile (NC) and azido (N) groups in their previously studied analogs. The CN stretch frequencies in 1 and 2 are red-shifted from those in their nitrile analogs but more blue-shifted from the NC and N stretch frequencies in their isonitrile and azido analogs.

Isonitrile as an Ultrasensitive Infrared Reporter of Hydrogen-Bonding Structure and Dynamics.

Infrared (IR) probes based on terminally blocked β-isocyanoalanine (AlaNC) and p-isocyanophenylalanine (PheNC) amino acids were synthesized. These isonitrile (NC)-derivatized compounds were extensively characterized by FTIR and femtosecond IR pump-probe spectroscopies, and a direct comparison was made with popularly used nitrile (CN)- and azide (N)-derivatized analogs. It is shown that the isonitrile stretch frequency exhibits extremely high sensitivity to hydrogen-bonding interactions.

Quantum Beats and Phase Shifts in Two-Dimensional Electronic Spectra of Zinc Naphthalocyanine Monomer and Aggregate.

The origin of quantum coherence in two-dimensional (2D) electronic spectra of molecular aggregates and light-harvesting complexes still remains an open question. In particular, it could be challenging to distinguish between electronic and vibrational coherences for a coupled system, where both degrees of freedom can be simultaneously excited. In this Letter, we examine quantum beats in the 2D spectra of zinc naphthalocyanine (ZnNc) aggregate and monomer, and compare their characteristic features in terms of the frequency and relative phase of diagonal and off-diagonal amplitude oscillations.

β-Isocyanoalanine as an IR probe: comparison of vibrational dynamics between isonitrile and nitrile-derivatized IR probes.

An infrared (IR) probe based on isonitrile (NC)-derivatized alanine 1 was synthesized and the vibrational properties of its NC stretching mode were investigated using FTIR and femtosecond IR pump-probe spectroscopy. It is found that the NC stretching mode is very sensitive to the hydrogen-bonding ability of solvent molecules. Moreover, its transition dipole strength is larger than that of nitrile (CN) in nitrile-derivatized IR probe 2.

Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease.

A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer's disease (AD). SAR studies were performed to optimize inhibitory activity on Aβ-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aβ-RAGE binding.

Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy.

Regulation of NF-κB activation through the inhibition of IKKβ has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKKβ inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKKβ inhibitors.

Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid.

Aggregated β-amyloid (Aβ) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of Aβ aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce Aβ-induced cytotoxicity by inhibiting Aβ aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (Aβ burden assay).

Infrared probing of 4-azidoproline conformations modulated by azido configurations.

4-Azidoproline (Azp) can tune the stability of the polyproline II (P(II)) conformation in collagen. The azido group in the 4R and 4S configurations stabilizes and destabilizes the P(II) conformation, respectively. To obtain insights into the dependence of the conformational stability on the azido configuration, we carried out Fourier transform (FT) IR experiments with four 4-azidoproline derivatives, Ac-(4R/S)-Azp-(NH/O)Me.

Phosphorylation alters backbone conformational preferences of serine and threonine peptides.

Despite the notion that a control of protein function by phosphorylation works mainly by inducing its conformational changes, the phosphorylation effects on even small peptide conformation have not been fully understood yet. To study its possible effects on serine and threonine peptide conformations, we recently carried out pH- and temperature-dependent circular dichroism (CD) as well as (1)H NMR studies of the phosphorylated serine and threonine peptides and compared them with their unphosphorylated analogs. In the present article, by performing the self-consistent singular value decomposition analysis of the temperature-dependent CD spectra and by analyzing the (3)J(H(N),H(α)) coupling constants extracted from the NMR spectra, the populations of the polyproline II (PPII) and β-strand conformers of the phosphorylated Ser and Thr peptides are determined.

Switching regioselectivity in crossed acyloin condensations between aromatic aldehydes and acetaldehyde by altering N-heterocyclic carbene catalysts.

An unprecedented high level of regioselectivities (up to 96%) in the intermolecular crossed acyloin condensations of various aromatic aldehydes with acetaldehyde was realized by an appropriate choice of N-heterocyclic carbene catalysts.

Azido gauche effect on the backbone conformation of β-azidoalanine peptides.

To study the azido gauche effect on the backbone conformation of β-azidoalanine (Aza) dipeptide (AAD, Ac-Aza-NHMe) and tripeptide (AAT, Ac-Aza-Aza-NH(2)), we used spectroscopic methods in combination with quantum chemistry calculations and molecular dynamics (MD) simulations. From the (1)H NMR coupling constants and (1)H,(1)H NOESY experimental data, we found that AAD in water mainly adopts a seven-membered cyclic (C(7)) rather than polyproline II (P(II)) backbone conformation and prefers the gauche- (g(-)) side-chain conformer. From the amide I IR absorption and circular dichroism (CD) spectra, the backbone conformation of AAD in water is found to deviate from P(II) but is rather close to C(7).

Site-selective intramolecular hydrogen-bonding interactions in phosphorylated serine and threonine dipeptides.

To study the phosphorylation effect on the peptide conformation, we carried out nuclear magnetic resonance (NMR), circular dichroism (CD), Fourier transform (FT)-IR, and vibrational circular dichroism (VCD) experiments with serine and threonine dipeptides (SD and TD) and their phosphorylated ones (pSD and pTD). It is found that both unphosphorylated and phosphorylated serine and threonine dipeptides adopt two conformations, polyproline II (P(II)) and beta-strand. The pH-dependent NMR study shows that the side-chain dianionic phosphoryl group can form direct intramolecular hydrogen bonds with the backbone amide protons at both the acetyl and amide ends of pTD, but only at the acetyl end of pSD.

Beta-azidoalanine as an IR probe: application to amyloid Abeta(16-22) aggregation.

Beta-azidoalanine dipeptide 1 was synthesized, and its azido stretching vibration in H2O and dimethyl sulfoxide (DMSO) was studied by using Fourier transform (FT) IR spectroscopy. The dipole strength of the azido stretch mode is found to be about 19 and 5 times larger than those of the CN and SCN stretch modes, respectively, which have been used as local environmental IR sensors. The azido stretch band in H2O is blue-shifted by about 14 cm(-1) in comparison to that in DMSO, indicative of its sensitivity to the electrostatic environment.

Photolytic control and infrared probing of amide I mode in the dipeptide backbone-caged with the 4,5-dimethoxy-2-nitrobenzyl group.

Alanine dipeptide analog 1 backbone-caged with a photolabile linker, 4,5-dimethoxy-2-nitrobenzyl (DmNb), was synthesized. UV-pulse-induced photochemical reaction of 1 was monitored by Fourier transform IR absorption spectroscopy under a steady-state condition or in a fast-scan mode. Upon photolysis of 1, the amide I band is changed from a doublet to a singlet with concomitant line shape changes of several IR bands.

Dipeptide structure determination by vibrational circular dichroism combined with quantum chemistry calculations.

The solution structure and the local solvation environments of alanine dipeptide (AD, 1 a) and its isotopomer (AD*, 1 b, 13C on the acetyl end C==O) are studied by using infrared (IR) spectroscopy and vibrational circular dichroism (VCD). From the amide I IR spectra of AD* in various protic solvents, it is found that each of the two carbonyl groups is fully H-bonded to two water molecules. However, the number of alcohol molecules H-bonded to each C==O varies from one to two, and the local solvation environments are asymmetric around the two peptides of AD* in alcohol solutions.

Phosphorylation effect on the GSSS peptide conformation in water: infrared, vibrational circular dichroism, and circular dichroism experiments and comparisons with molecular dynamics simulations.

The phosphorylation effect on the small peptide conformation in water has not been clearly understood yet, despite the widely acknowledged notion that control of protein activity by phosphorylation works mainly by inducing conformational change. To elucidate the detailed mechanism, we performed infrared (IR) absorption and vibrational and electronic circular dichroism studies of both unphosphorylated and phosphorylated tetrapeptides, GSSS 1 and GSSpS 2. The solution structure of the tetrapeptide is found to be little dependent on the presence of the neutral or negatively charged phosphoryl group, and to be a mixture of extended structures including polyproline II (PII) and beta-sheet conformations.