Inhibition of vibrational energy flow within an aromatic scaffold via heavy atom effect.

The regulation of intramolecular vibrational energy redistribution (IVR) to influence energy flow within molecular scaffolds provides a way to steer fundamental processes of chemistry, such as chemical reactivity in proteins and design of molecular diodes. Using two-dimensional infrared (2D IR) spectroscopy, changes in the intensity of vibrational cross-peaks are often used to evaluate different energy transfer pathways present in small molecules. Previous 2D IR studies of para-azidobenzonitrile (PAB) demonstrated that several possible energy pathways from the N3 to the cyano-vibrational reporters were modulated by Fermi resonance, followed by energy relaxation into the solvent [Schmitz et al.

Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism.

Polymeric vehicles that efficiently package and controllably release nucleic acids enable the development of safer and more efficacious strategies in genetic and polynucleotide therapies. Developing delivery platforms that endogenously monitor the molecular interactions, which facilitate binding and release of nucleic acids in cells, would aid in the rational design of more effective vectors for clinical applications. Here, we report the facile synthesis of a copolymer containing quinine and 2-hydroxyethyl acrylate that effectively compacts plasmid DNA (pDNA) through electrostatic binding and intercalation.

Extending the vibrational lifetime of azides with heavy atoms.

The development of novel vibrational reporters (VRs), aka infrared (IR) probes, to study local environments and dynamic processes in biomolecules and materials continues to be an important area of research. Azides are important VRs because of their small size and large transition dipole strengths, however, their relatively short vibrational lifetimes (<2 ps) have limited their full potential. Herein we report that the vibrational lifetimes of azides can be increased by attaching them to heavy atoms and by using heavy 15N isotopes.

2D-IR studies of cyanamides (NCN) as spectroscopic reporters of dynamics in biomolecules: Uncovering the origin of mysterious peaks.

Cyanamides (NCN) have been shown to have a larger transition dipole strength than cyano-probes. In addition, they have similar structural characteristics and vibrational lifetimes to the azido-group, suggesting their utility as infrared (IR) spectroscopic reporters for structural dynamics in biomolecules. To access the efficacy of NCN as an IR probe to capture the changes in the local environment, several model systems were evaluated via 2D IR spectroscopy.

Unperturbed Detection of the Dynamic Structure in the Hydrophobic Core of Trp-Cage via Two-Dimensional Infrared Spectroscopy.

The tyrosine ring mode is an intrinsic non-perturbing site-specific infrared reporter for conformational dynamics within protein systems. This transition is influenced by direct and indirect interactions associated with the electron-donating ability and the hydrophobicity of the surrounding molecules. Utilizing an intrinsic tyrosine moiety, two-dimensional infrared spectra of Trp-cage, often called the "hydrogen atom" of protein folding, were measured in the folded and denatured states to uncover the dynamics of the hydrophobic core.

Tuning Molecular Vibrational Energy Flow within an Aromatic Scaffold via Anharmonic Coupling.

From guiding chemical reactivity in synthesis or protein folding to the design of energy diodes, intramolecular vibrational energy redistribution harnesses the power to influence the underlying fundamental principles of chemistry. To evaluate the ability to steer these processes, the mechanism and time scales of intramolecular vibrational energy redistribution through aromatic molecular scaffolds have been assessed by utilizing two-dimensional infrared (2D IR) spectroscopy. 2D IR cross peaks reveal energy relaxation through an aromatic scaffold from the azido- to the cyano-vibrational reporters in -azidobenzonitrile (PAB) and -(azidomethyl)benzonitrile (PAMB) prior to energy relaxation into the solvent.

New Insights into Quinine-DNA Binding Using Raman Spectroscopy and Molecular Dynamics Simulations.

Quinine's ability to bind DNA and potentially inhibit transcription and translation has been examined as a mode of action for its antimalarial activity. UV absorption and fluorescence-based studies have lacked the chemical specificity to develop an unambiguous molecular-level picture of the binding interaction. To address this, we use Raman spectroscopy and molecular dynamics (MD) to investigate quinine-DNA interactions.

Synthesis of 5-Cyano-Tryptophan as a Two-Dimensional Infrared Spectroscopic Reporter of Structure.

A concise synthesis of protected 5-cyano-l-tryptophan (Trp ) has been developed for 2D IR spectroscopic investigations within either peptides or proteins. To assess the potential of differently substituted cyano-tryptophans, several model cyano-indole systems were characterized using IR spectroscopy. Upon assessment of their spectroscopic properties, Trp was integrated into a model peptide sequence, Trp -Gly-Phe , to elucidate its structure.

Two-Dimensional Infrared Study of Vibrational Coupling between Azide and Nitrile Reporters in a RNA Nucleoside.

The vibrations in the azide, N3, asymmetric stretching region and nitrile, CN, symmetric stretching region of 2'-azido-5-cyano-2'-deoxyuridine (N3CNdU) are examined by two-dimensional infrared (2D IR) spectroscopy. At earlier waiting times, the 2D IR spectrum shows the presence of both vibrational transitions along the diagonal and off-diagonal cross peaks indicating vibrational coupling. The coupling strength is determined from the off-diagonal anharmonicity to be 66 cm(-1) for the intramolecular distance of ∼7.

Synthesis and Evaluation of the Sensitivity and Vibrational Lifetimes of Thiocyanate and Selenocyanate Infrared Reporters.

Two novel 2'-deoxyadenosine (dA) analogues, Si-dA-SCN and Si-dA-SeCN, and two novel phenylalanine (Phe) analogues, Boc-Me-PheCHSCN and Boc-Me-PheCHSeCN, have been synthesized and the thiocyanate (SCN) and selenocyanate (SeCN) functional groups evaluated as vibrational reporters. The syntheses of Si-dA-SCN and Si-dA-SeCN were accomplished in three steps in 16% and 32% overall yields, respectively, and the syntheses of Boc-Me-PheCHSCN and Boc-Me-PheCHSeCN were completed in four steps in 8.9% and 2.