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Lens is the avascular tissue in the eye between the aqueous humor and vitreous. Drug binding to the lens might affect ocular pharmacokinetics, and the binding may also have a pharmacological role in drug-induced cataract and cataract treatment. Drug distribution in the lens has been studied in vitro with many compounds; however, the experimental methods vary, no detailed information on distribution between the lens sublayers exist, and the partition coefficients are reported rarely. Therefore, our objectives were to clarify drug localization in the lens layers and establish partition coefficients for a wide range of molecules. Furthermore, we aimed to illustrate the effect of lenticular drug binding on overall ocular drug pharmacokinetics. We studied the distribution of 16 drugs and three fluorescent dyes in whole porcine lenses in vitro with imaging mass spectrometry and fluorescence microscopy techniques. Furthermore, we determined lens/buffer partition coefficients with the same experimental setup for 28 drugs with mass spectrometry. Finally, the effect of lenticular binding of drugs on aqueous humor drug exposure was explored with pharmacokinetic simulations. After 4 h, the drugs and the dyes distributed only to the outermost lens layers (capsule and cortex). The lens/buffer partition coefficients for the drugs were low, ranging from 0.05 to 0.8. On the basis of the pharmacokinetic simulations, a high lens-aqueous humor partition coefficient increases drug exposure in the lens but does not significantly alter the pharmacokinetics in the aqueous humor. To conclude, the lens seems to act mainly as a physical barrier for drug distribution in the eye, and drug binding to the lens affects mainly the drug pharmacokinetics in the lens.

Azines are important in many extraterrestrial environments, from the atmosphere of Titan to the interstellar medium. They have been implicated as possible carriers of the diffuse interstellar bands in astronomy, indicating their persistence in interstellar space. Most importantly, they constitute the basic building blocks of DNA and RNA, so their chemical reactivity in these environments has significant astrobiological implications. In addition, N and O atoms are widely observed in the ISM and in the ionospheres of planets and moons. However, the chemical reactions of molecular anions with abundant interstellar and atmospheric atomic species are largely unexplored. In this paper, gas-phase reactions of deprotonated anions of benzene, pyridine, pyridazine, pyrimidine, pyrazine, and s-triazine with N and O atoms are studied both experimentally and computationally. In all cases, the major reaction channel is associative electron detachment; these reactions are particularly important since they control the balance between negative ions and free electron densities. The reactions of the azine anions with N atoms exhibit larger rate constants than reactions of corresponding chain anions. The reactions of azine anions with O atoms are even more rapid, with complex product patterns for different reactants. The mechanisms are studied theoretically by employing density functional theory; spin conversion is found to be important in determining some product distributions. The rich gas-phase chemistry observed in this work provides a better understanding of ion-atom reactions and their contributions to ionospheric chemistry as well as the chemical processing that occurs in the boundary layers between diffuse and dense interstellar clouds.

Rate constants were measured at 300 K for the reactions of the hydride anion, H-, with neutral molecules C2H2, H2O, CH3CN, CH3OH, (CH3)2CO, CH3CHO, N2O, CO2, O2, CO, CH3Cl, (CH3)3CCl, (CH3CH2)2O, C6H6, and D2 using a flowing-afterglow instrument. Experimental work was supplemented by ab initio calculations to provide insight into the viability of reaction pathways. Our reported rate constants should prove useful to models of astrophysical environments where conditions prevail for the existence of both H- and neutral species. The variety of neutral reactants studied includes representative species from prototypical chemical groups, effectively mapping reactivity trends for the hydride anion.