Stability and Structure of Potentially Atmospherically Relevant Glycine Ammonium Bisulfate Clusters.

New particle formation (NPF) is the process by which trace atmospheric acids and bases cluster and grow into particles that ultimately impact climate. Sulfuric acid concentration drives NPF, but nitrogen-containing bases promote the formation of more stable clusters via salt bridge formation. Recent computational efforts have suggested that amino acids can enhance NPF, predicting that they can stabilize new particles via multiple protonation sites, but there has yet to be experimental validation of these predictions. We used mass spectrometry and infrared spectroscopy to study the structure and stability of cationic clusters composed of glycine, sulfuric acid, and ammonia. When collisionally activated, clusters were significantly more likely to eliminate ammonia or sulfuric acid than glycine, while quantum chemical calculations predicted lower binding free energies for ammonia but similar binding free energies for glycine and sulfuric acid. These calculations predicted several low-energy structures, so we compared experimental and computed vibrational spectra to attempt to validate the computationally predicted minimum energy structure. Unambiguous identification of the experimental structure by comparison to these calculations was made difficult by the complexity of the experimental spectra and the fact that the identity of the computed lowest-energy structure depended strongly on temperature. If their vapors are present, amino acids are likely to be enriched in new particles by displacing more weakly bound ammonia, similar to the behavior of other atmospheric amines. The carboxylic acid groups were found to preferentially interact with other carboxylic acids, suggesting incipient organic/inorganic phase separation even at these small sizes.

Metal-Mediated, Autolytic Amide Bond Cleavage: A Strategy for the Selective, Metal Complexation-Catalyzed, Controlled Release of Metallodrugs.

Activation of metalloprodrugs or prodrug activation using transition metal catalysts represents emerging strategies for drug development; however, they are frequently hampered by poor spatiotemporal control and limited catalytic turnover. Here, we demonstrate that metal complex-mediated, autolytic release of active metallodrugs can be successfully employed to prepare clinical grade (radio-)pharmaceuticals. Optimization of the Lewis-acidic metal ion, chelate, amino acid linker, and biological targeting vector provides means to release peptide-based (radio-)metallopharmaceuticals in solution and from the solid phase using metal-mediated, autolytic amide bond cleavage (MMAAC). Our findings indicate that coordinative polarization of an amide bond by strong, trivalent Lewis acids such as Ga3+ and Sc3+ adjacent to serine results in the N, O acyl shift and hydrolysis of the corresponding ester without dissociation of the corresponding metal complex. Compound [68Ga]Ga-10, incorporating a cleavable and noncleavable functionalization, was used to demonstrate that only the amide bond-adjacent serine effectively triggered hydrolysis in solution and from the solid phase. The corresponding solid-phase released compound [68Ga]Ga-8 demonstrated superior in vivo performance in a mouse tumor model compared to [68Ga]Ga-8 produced using conventional, solution-phase radiolabeling. A second proof-of-concept system, [67Ga]Ga-17A (serine-linked) and [67Ga]Ga-17B (glycine-linked) binding to serum albumin via the incorporated ibuprofen moiety, was also synthesized. These constructs demonstrated that complete hydrolysis of the corresponding [68Ga]Ga-NOTA complex from [67Ga]Ga-17A can be achieved in naïve mice within 12 h, as traceable in urine and blood metabolites. The glycine-linked control [68Ga]Ga-17B remained intact. Conclusively, MMAAC provides an attractive tool for selective, thermal, and metal ion-mediated control of metallodrug activation compatible with biological conditions.

Spectroscopic Studies of Clusters of Atmospheric Relevance.

Atmospheric aerosols exert a significant but highly uncertain effect on the global climate, and roughly half of these particles originate as small clusters formed by collisions between atmospheric trace vapors. These particles typically consist of acids, bases, and water, stabilized by salt bridge formation and a network of strong hydrogen bonds. We review spectroscopic studies of this process, focusing on the clusters likely to be involved in the first steps of particle formation and the intermolecular interactions governing their stability. These studies typically focus on determining structure and stability and have shown that acid-base chemistry in the cluster may violate chemical intuition derived from solution-phase behavior and that hydration of these clusters is likely to be complex to describe. We also suggest fruitful areas for extension of these studies and alternative spectroscopic techniques that have not yet been applied to this problem.

Propane and propane-water interactions: a study at cryogenic temperatures.

The phase transition of solid propane and a propane-water mixture under ultrahigh vacuum has been investigated using reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption mass spectrometry (TPD-MS). Here, the investigation is divided into two sections: the phase transition of pure propane and the interaction of propane with water. RAIR spectra of pure propane reveal an unknown crystalline phase at 50 K (phase I), which gradually converts to a known crystalline phase (phase II) at higher temperature. This conversion is associated with certain kinetics. Co-deposition of water and propane restricts the amorphous to crystalline phase transition, while sequential deposition (H2O@C3H8; propane over predeposited water) does not hinder it. For an alternative sequential deposition (C3H8@H2O; water over predeposited propane), the phase transition is hindered due to diffusional mixing within the given experimental time, which is attributed to the reason behind the restricted phase transition.