Nitric Oxide-Releasing Cyclodextrins

Abstract

A series of secondary amine-modified cyclodextrin (CD) derivatives were synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6–2.4 µmol/mg) and release half-lives (0.7–4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donor. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa, a Gram-negative pathogen with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated hepta-substituted CD derivatives exhibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug releasing therapeutic.

Chiral Brønsted Acid and Gold Catalyzed Enantioselective Synthesis of 1,8‐Dihydroindeno[2,1‐b]pyrroles

“…Following this latter order of addition, the analogous reaction at a lower catalyst loading of 2.5 mol% of the Au(I) complex was found to give a comparable product ee value of 97% but a lower product yield of 80% (entry 4). In a final set of control experiments under the conditions described in entry 1, a survey of AgOAc, AgOTf, Cu(OTf) 2 or CuI in place of the Au(I) salt added after 0.5 h was shown to afford the 1H-indene 5 a as the only product in near quantitative yield after 48 h (entries [6][7][8][9].…”

“…This could involve the initial formation of the chiral contact ion-pair intermediate I as a result of dehydration of the substrate 4 by (S)-A and association of the ensuing carbocation species with the Ntriflyl phosphoramide anion. [8] This is followed by DNE to give the 1H-indene adduct 5 with the (8R) absolute configuration provided by the well-defined stereochemical environment of I that is assisted by hydrogen bonding interactions between the amino group in the substrate cation and catalyst anion. Subsequent activation of the alkyne moiety in the newly formed carbocycle by the presence of the gold (I) salt would give the metal-coordinated adduct II.…”

“…With this in mind, we were drawn to the potential reactivity of electron-rich aryl and 2-thienyl vinyl b-amino alcohols (Scheme 1b). [7,8] We had previously reported the substrate class to undergo chiral Brønsted acid-catalyzed asymmetric DNE to give the corresponding 1H-indene and 4H-cyclopenta [b] thiophene derivatives. Building on this initial study, we reasoned that a sequential one-pot gold(I)-mediated CÀN bond formation step might be possible in instances where the in situ formed carbocyclic adduct contained both an alkyne group and an amino motif (Scheme 1c).…”

Recent Advances and Future Prospects on Adaptive Biomaterials for Antimicrobial Applications

“…NO is highly reactive and normally its N ‐diazeniumdiolate counterparts were used. N ‐diazeniumdiolate NO donors are formed via the reaction of NO gas with amines located on nanocarriers under basic conditions and high pressure . Under the acidic microenvironment of a biofilm, N ‐diazeniumdiolate will degrade and release NO in situ to eradicate bacterial biofilms formed by either Gram‐positive or Gram‐negative strains .…”

“…Under the acidic microenvironment of a biofilm, N ‐diazeniumdiolate will degrade and release NO in situ to eradicate bacterial biofilms formed by either Gram‐positive or Gram‐negative strains . Special attention should be paid to the half‐life of N ‐diazeniumdiolate, which ranges from several seconds to several hours …”