Poly(malic acid) Nanoconjugates of Pyrazinoic Acid for Lung Delivery in the Treatment of Tuberculosis.

Tuberculosis (TB) remains a major global infection, and TB treatments could be improved by site-specific targeting with delivery systems that allow tissue and cell uptake. To increase the drug concentration at the target sites following lung delivery, polymeric nanoconjugates based on biodegradable poly(malic acid) were designed. Pyrazinoic acid (POA), the active moiety of pyrazinamide─a first-line antituberculosis drug─was covalently bound to poly(malic acid) using a hydrophobic linker at mole ratios of 25%, 50%, and 75%.

Post-Modification of Copolymers Obtained by ATRP for an Application in Heterogeneous Asymmetric Salen Catalysis.

Copolymers are valuable supports for obtaining heterogeneous catalysts that allow their recycling and therefore substantial savings, particularly in the field of asymmetric catalysis. This contribution reports the use of two comonomers: Azido-3-propylmethacrylate (AZMA) bearing a reactive azide function was associated with 2-methoxyethyl methacrylate (MEMA), used as a spacer, for the ATRP synthesis of copolymers, and then post-functionalized with a propargyl chromium salen complex. The controlled homopolymerization of MEMA by ATRP was firstly described and proved to be more controlled in molar mass than that of AZMA for conversions up to 63%.

N-H⋯X interactions stabilize intra-residue C5 hydrogen bonded conformations in heterocyclic α-amino acid derivatives.

Nature makes extensive and elaborate use of hydrogen bonding to assemble and stabilize biomolecular structures. The shapes of peptides and proteins rely significantly on N-H⋯O[double bond, length as m-dash]C interactions, which are the linchpins of turns, sheets and helices. The C5 H-bond, in which a single residue provides both donor and acceptor, is generally considered too weak to force the backbone to adopt extended structures.

Conformation control through concurrent N-H⋯S and N-H⋯O[double bond, length as m-dash]C hydrogen bonding and hyperconjugation effects.

In addition to the classical N-H⋯O[double bond, length as m-dash]C non-covalent interaction, less conventional types of hydrogen bonding, such as N-H⋯S, may play a key role in determining the molecular structure. In this work, using theoretical calculations in combination with spectroscopic analysis in both gas phase and solution phase, we demonstrate that both these H-bonding modes exist simultaneously in low-energy conformers of capped derivatives of Attc, a thietane α-amino acid. 6-Membered ring inter-residue N-H⋯S interactions (C6), assisted by hyperconjugation between the thietane ring and the backbone, combine with 5-membered ring intra-residue backbone N-H⋯O[double bond, length as m-dash]C interactions (C5) to provide a C5-C6 feature that stabilizes a planar geometry in the monomer unit.

A theoretical and experimental case study of the hydrogen bonding predilection of S-methylcysteine.

S-containing amino acids can lead to two types of local NH···S interactions which bridge backbone NH sites to the side chain to form either intra- or inter-residue H-bonds. The present work reports on the conformational preferences of S-methyl-L-cysteine, Cys(Me), using a variety of investigating tools, ranging from quantum chemistry simulations, gas-phase UV and IR laser spectroscopy, and solution state IR and NMR spectroscopies, on model compounds comprising one or two Cys(Me) residues. We demonstrate that in gas phase and in low polarity solution, the C- and N-capped model compound for one Cys(Me) residue adopts a preferred C5-C6γ conformation which combines an intra-residue N-H···O=C backbone interaction (C5) and an inter-residue N-H···S interaction implicating the side-chain sulfur atom (C6γ).