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4-aminobenzoic acid (4ABA) is a model scaffold for studying solvent-mediated proton transfer. Although protonation at the carboxylic group ( O-protomer) is energetically favored in the gas phase, the N-protomer, where the proton remains on the amino group, can be kinetically trapped by electrospray ionization of 4ABA in an aprotic solvent such as acetonitrile. Here, we report the formation of the hydrated deuterium isotopologues of the N-protomers, RND3+·(H2O) n=1–3, (R = C6H4COOD), which are generated by condensing water molecules onto the bare N-protomers in a liquid nitrogen cooled, radiofrequency octopole ion trap at 80 K. The product clusters are then transferred to a 20 K cryogenic ion trap where they are tagged with weakly bound D2 molecules. The structures of these clusters are determined by analysis of their vibrational patterns, obtained by resonant IR photodissociation. The resulting patterns confirm that the metastable N-protomer configuration remains intact even when warmed by the sequential condensation of water molecules. The attachment of H2O molecules onto the RND3+ head group also affords the opportunity to explore the possibility of H/D exchange between the acid scaffold and the proximal water network. The spectroscopic results establish that although the RND3+·(H2O) n=1,2 clusters are formed without H/D exchange, the n = 3 cluster exhibits about 10% H/D exchange as evidenced by the appearance of the telltale HOD bands. The site of exchange on the acid is determined to be the acidic OH group by the emergence of the OH stretching fundamental in the –COOH motif.

We determine the intramolecular distortions at play in the 2-hydroxyethylhydrazinium nitrate (HEHN) ionic liquid (IL) propellant, which presents the interesting case that the HEH+ cation has multiple sites (i.e., hydroxy, primary amine, and secondary ammonium groups) available for H-bonding with the nitrate anion. These interactions are quantified by analyzing the vibrational band patterns displayed by cold cationic clusters, (HEH+)n(NO3-)n-1, n = 2-6, which are obtained using IR photodissociation of the cryogenically cooled, mass-selected ions. The strong interaction involving partial proton transfer of the acidic N-H proton in HEH+ cation to the nitrate anion is strongly enhanced in the ternary n = 2 cluster but is suppressed with increasing cluster size. The cluster spectra recover the bands displayed by the bulk liquid by n = 5, thus establishing the minimum domain required to capture this aspect of macroscopic behavior.

Decoding the structural information contained in the interfacial vibrational spectrum of water requires understanding how the spectral signatures of individual water molecules respond to their local hydrogen bonding environments. In this study, we isolated the contributions for the five classes of sites that differ according to the number of donor (D) and acceptor (A) hydrogen bonds that characterize each site. These patterns were measured by exploiting the unique properties of the water cluster cage structures formed in the gas phase upon hydration of a series of cations M+·(H2O)n (M = Li, Na, Cs, NH4, CH3NH3, H3O, and n = 5, 20-22). This selection of ions was chosen to systematically express the A, AD, AAD, ADD, and AADD hydrogen bonding motifs. The spectral signatures of each site were measured using two-color, IR-IR isotopomer-selective photofragmentation vibrational spectroscopy of the cryogenically cooled, mass selected cluster ions in which a single intact H2O is introduced without isotopic scrambling, an important advantage afforded by the cluster regime. The resulting patterns provide an unprecedented picture of the intrinsic line shapes and spectral complexities associated with excitation of the individual OH groups, as well as the correlation between the frequencies of the two OH groups on the same water molecule, as a function of network site. The properties of the surrounding water network that govern this frequency map are evaluated by dissecting electronic structure calculations that explore how changes in the nearby network structures, both within and beyond the first hydration shell, affect the local frequency of an OH oscillator. The qualitative trends are recovered with a simple model that correlates the OH frequency with the network-modulated local electron density in the center of the OH bond.

We report vibrational spectra of the H

The reduction of carbon dioxide to oxalate has been studied by experimental Collisionally Induced Dissociation (CID) and vibrational characterization of the alkali metal oxalates, supplemented by theoretical electronic structure calculations. The critical step in the reductive process is the coordination of CO2 to an alkali metal anion, forming a metal carbonite MCO2− able to subsequently receive a second CO2 molecule. While the energetic demand for these reactions is generally low, we find that the degree of activation of CO2 in terms of charge transfer and transition state energies is the highest for lithium and systematically decreases down the group (M = Li–Cs). This is correlated to the strength of the binding interaction between the alkali metal and CO2, which can be related to the structure of the oxalate moiety within the product metal complexes evolving from a planar to a staggered conformer with increasing atomic number of the interacting metal. Similar structural changes are observed for crystalline alkali metal oxalates, although the C2O42− moiety is in general more planar in these, a fact that is attributed to the increased number of interacting alkali metal cations compared to the gas-phase ions.

We report the binding geometries of the isomers that are formed when the hydrogen oxalate ((CO2)2H=HOx) anion attaches to dinuclear coinage metal phosphine complexes of the form [M1M2dcpm2(HOx)]+ with M=Cu, Ag and dcpm=bis(dicyclohexylphosphino)methane, abbreviated [MM]+ . These structures are established by comparison of isomer‐selective experimental vibrational band patterns displayed by the cryogenically cooled and N2‐tagged cations with DFT calculations of the predicted spectra for various local minima. Two isomeric classes are identified that feature either attachment of the carboxylate oxygen atoms to the two metal centers (end‐on docking) or attachment of oxygen atoms on different carbon atoms asymmetrically to the metal ions (side‐on docking). Within each class, there are additional isomeric variations according to the orientation of the OH group. This behavior indicates that HOx undergoes strong and directional coordination to [CuCu]+ but adopts a more flexible coordination to [AgAg]+ . Infrared spectra of the bare ions, fragmentation thresholds and ion mobility measurements are reported to explore the behaviors of the complexes at ambient temperature., To characterize the binding motifs of hydrogen oxalate (HOx) onto copper (Cu) and silver (Ag) phosphine complexes, we have invastigated [M1M2dcpm2(HOx)]+ (M=Cu, Ag; dcpm=bis(dicyclohexylphosphino)methane; abbreviated [CuCu]+ and [AgAg]+ ) in isolation. The 40 K N2 tagged IR‐PD spectra gives evidence for two isomers of [CuCu]+ and three isomers of [AgAg]+ , supported by DFT calculations. Two color IR‐IR hole burning experiments indicate some minor amount of isomeric interconversions in [AgAg]+ , whereas [CuCu]+ reveals a stiffer HOx coordination.

During adolescence, the lungs expand while alveoli increase greatly in number. A precise and deep understanding of the biological processes responsible for the many fold increase in alveoli during adolescence could form the foundation for novel treatments to reoptimize lung function after disease or injury. Herein we provide a unique insight into the alveolar growth in the mouse lung during first postnatal 4 weeks herein described as the adolescence phase. Using 3-Dimensionnal (3D) high-resolution large field of view optical imaging coupled with qualitative and quantitative analysis, we suggest the bulk of alveolarization during adolescent lung growth occurs while the surface to volume of the acinar volume remains constant. The most distal 10 or more bifurcations within the acinar saccular region, comprised of small ducts and alveoli, are of similar scale. We explored the connections between the growth of lung and it’s structural and functional parameters, by comparing the correlations between alveolar size, surface area of gas exchange regions, breathing rate, metabolic rate, and oxygen demand across mammalian species which exhibit widely divergent body sizes.

The reduction of carbon dioxide to oxalate has been studied by experimental Collisionally Induced Dissociation (CID) and vibrational characterization of the alkali metal oxalates, supplemented by theoretical electronic structure calculations. The critical step in the reductive process is the coordination of CO2 to an alkali metal anion, forming a metal carbonite MCO2- able to subsequently receive a second CO2 molecule. While the energetic demand for these reactions is generally low, we find that the degree of activation of CO2 in terms of charge transfer and transition state energies is the highest for lithium and systematically decreases down the group (M = Li-Cs). This is correlated to the strength of the binding interaction between the alkali metal and CO2, which can be related to the structure of the oxalate moiety within the product metal complexes evolving from a planar to a staggered conformer with increasing atomic number of the interacting metal. Similar structural changes are observed for crystalline alkali metal oxalates, although the C2O42- moiety is in general more planar in these, a fact that is attributed to the increased number of interacting alkali metal cations compared to the gas-phase ions.

Background In short bowel syndrome, luminal factors influence adaptation in which the truncated intestine increases villus lengths and crypt depths to increase nutrient absorption. No study has evaluated the effect of adaptation within the distal intestine after intestinal separation. We evaluated multiple conditions, including Igf1r inhibition, in proximal and distal segments after intestinal resection to evaluate the epithelial effects of the absence of mechanoluminal stimulation. Methods Short bowel syndrome was created in adult male zebrafish by performing a proximal stoma with ligation of the distal intestine. These zebrafish with short bowel syndrome were compared to sham-operated zebrafish. Groups were treated with the Igf1r inhibitor NVP-AEW541, DMSO, a vehicle control, or water for 2 weeks. Proximal and distal intestine were analyzed by hematoxylin and eosin for villus epithelial circumference, inner epithelial perimeter, and circumference. We evaluated BrdU+ cells, including costaining for β-catenin, and the microbiome was evaluated for changes. Reverse transcription quantitative polymerase chain reaction was performed for β-catenin, CyclinD1, Sox9a, Sox9b, and c-Myc. Results Proximal intestine demonstrated significantly increased adaptation compared to sham-operated proximal intestine, whereas the distal intestine showed no adaptation in the absence of luminal flow. Addition of the Igf1r inhibitor resulted in decreased adaption in the distal intestine but an increase in distal proliferative cells and proximal β-catenin expression. While some proximal proliferative cells in short bowel syndrome colocalized β-catenin and BrdU, the distal proliferative cells did not co-stain for β-catenin. Sox9a increased in the distal limb after division but not after inhibition with the Igf1r inhibitor. There was no difference in alpha diversity or species richness of the microbiome between all groups. Conclusion Luminal flow in conjunction with short bowel syndrome significantly increases intestinal adaption within the proximal intestine in which proliferative cells contain β-catenin. Addition of an Igf1r inhibitor decreases adaptation in both proximal and distal limbs while increasing distal proliferative cells that do not colocalize β-catenin. Igf1r inhibition abrogates the increase in distal Sox9a expression that otherwise occurs in short bowel syndrome. Mechanoluminal flow is an important stimulus for intestinal adaptation.

4-Aminobenzoic acid (4ABA) is a biologically relevant, small organic molecule with two protonation sites: the amino group (N-protomer) and the carboxyl group (O-protomer). The O-protomer is energetically preferred in the gas-phase, while the higher energy N-protomer can be trapped using aprotic solvents such as acetonitrile during electrospray ionization. Here, we focus on the structure of the O-protomer, which can occur in three low-lying isomeric forms that result from different orientations of the OH groups relative to the benzene ring. We report the vibrational spectra of both N- and O-protomers of the cryogenically cooled ions in the gas phase over the spectral range 800-4000 cm-1. The bands arising from the OH stretches are isolated from the nearby NH stretching fundamentals using isotopic labeling as well as by analysis of the shifts in these fundamentals upon attachment of D2 and N2 molecules to the OH groups of the O-protomer. The spectra of isomers derived from the different locations of the adducts were isolated using two-color, IR-IR photofragmentation spectroscopy. The docking motifs by which the O-protomer binds to another 4ABA molecule is also explored and found to feature a bifurcated arrangement involving attachment of both OH groups of the protonated head group to the carbonyl group of the neutral partner.

Prussian blue analogs (PBAs) are versatile materials with a wide range of applications. Due to their tunability, intrinsic biocompatibility, as well as low toxicity, these nanoscale coordination polymers have been successfully studied as multimodal contrast agents for multiple imaging techniques. Herein, we report the expanded biomedical application of PBAs to X-ray computed tomography (CT). In our systematic study of the series A{Mn^(II)[Fe^(III)(CN)6]} (A = K^+, Rb^+, Cs^+), we showed that derivatives incorporating Rb+ and Cs+ ions in the tetrahedral sites of the parent face-centered cubic cyano-bridged networks exhibited substantially increased X-ray attenuation coefficients, thus yielding significant contrast compared to the clinically approved X-ray contrast agent iohexol at the same concentrations. Additionally, our μ-CT studies revealed that these PBAs could be useful as dual-energy CT contrast agents for different biological specimens by using the lower varying scanning X-ray tube voltages. Finally, in vitro studies using U87-Luc cells treated with PBAs, including cellular CT imaging and bioluminescence cell viability assays, revealed that PBAs were taken up by the glioblastoma cells, with moderate biocompatibility at concentrations below the mM range.

Interaction between p-toluenesulfonic acid (pTSA) and water is studied at −20 °C in a CCl4 matrix. In CCl4 water exists as monomers with restricted rotational motion about its symmetry axis. Additionally, CCl4 is transparent in the hydrogen-bonded region; CCl4 thus constitutes an excellent ambient thermal energy matrix isolation medium for diagnosing interactions with water. Introducing pTSA-nH2O gives rise to two narrow resonances at 3642 cm–1 and at 2835 cm–1 plus a broad 3000–3550 cm–1 absorption. In addition, negative monomer symmetric and asymmetric stretch features relative to nominally dry CCl4 indicate that fewer water monomers exist in the cooled (−20 °C) acid solution than in room-temperature anhydrous CCl4. The negative peaks along with the broad absorption band indicate that water monomers are incorporated into clusters. The 3642 cm–1 resonance is assigned to the OH-π interaction with a cluster containing many water molecules per acid molecule. The 2835 cm–1 resonance is assigned to the (S-)O–...

Purpose Human pluripotent stem cell (hPSC)-derived retinal organoids are a platform for investigating retinal development, pathophysiology, and cellular therapies. In contrast to histologic analysis in which multiple specimens fixed at different times are used to reconstruct developmental processes, repeated analysis of the same living organoids provides a more direct means to characterize changes. New live imaging modalities can provide insights into retinal organoid structure and metabolic function during in vitro growth. This study employed live tissue imaging to characterize retinal organoid development, including metabolic changes accompanying photoreceptor differentiation. Methods Live hPSC-derived retinal organoids at different developmental stages were examined for microanatomic organization and metabolic function by phase contrast microscopy, optical coherence tomography (OCT), fluorescence lifetime imaging microscopy (FLIM), and hyperspectral imaging (HSpec). Features were compared to those revealed by histologic staining, immunostaining, and microcomputed tomography (micro-CT) of fixed organoid tissue. Results We used FLIM and HSpec to detect changes in metabolic activity as organoids differentiated into organized lamellae. FLIM detected increased glycolytic activity and HSpec detected retinol and retinoic acid accumulation in the organoid outer layer, coinciding with photoreceptor genesis. OCT enabled imaging of lamellae formed during organoid maturation. Micro-CT revealed three-dimensional structure, but failed to detect lamellae. Conclusions Live imaging modalities facilitate real-time and nondestructive imaging of retinal organoids as they organize into lamellar structures. FLIM and HSpec enable rapid detection of lamellar structure and photoreceptor metabolism. Live imaging techniques may aid in the continuous evaluation of retinal organoid development in diverse experimental and cell therapy settings.