Iron oxyhydroxide minerals, known to be chemically reactive and significant for elemental cycling, are thought to have been abundant in early-Earth seawater, sediments, and hydrothermal systems. In the anoxic Fe²⁺-rich early oceans, these minerals would have been only partially oxidized and thus redox-active, perhaps able to promote prebiotic chemical reactions. We show that pyruvate, a simple organic molecule that can form in hydrothermal systems, can undergo reductive amination in the presence of mixed-valence iron oxyhydroxides to form the amino acid alanine, as well as the reduced product lactate. Furthermore, geochemical gradients of pH, redox, and temperature in iron oxyhydroxide systems affect product selectivity. The maximum yield of alanine was observed when the iron oxyhydroxide mineral contained 1:1 Fe(II):Fe(III), under alkaline conditions, and at moderately warm temperatures. These represent conditions that may be found, for example, in iron-containing sediments near an alkaline hydrothermal vent system. The partially oxidized state of the precipitate was significant in promoting amino acid formation: Purely ferrous hydroxides did not drive reductive amination but instead promoted pyruvate reduction to lactate, and ferric hydroxides did not result in any reaction. Prebiotic chemistry driven by redox-active iron hydroxide minerals on the early Earth would therefore be strongly affected by geochemical gradients of E_h, pH, and temperature, and liquid-phase products would be able to diffuse to other conditions within the sediment column to participate in further reactions. Significance Amino acids are formed from simple organic precursors in iron oxyhydroxide mineral systems that contain geochemical gradients. Redox and pH gradients significantly impact reaction pathways: Amino acids only form when the mineral contains both oxidized and reduced iron, and when the surrounding solution is alkaline. This shows that aqueous, partially reducing iron mineral systems (which would have been common in early-Earth seafloor/vent environments) could have facilitated synthesis and concentration of prebiotic organic molecules relevant for the emergence of life. It also suggests that geochemical gradients in vent environments can drive product selectivity for prebiotic chemistry, perhaps leading to more complex organic reaction systems as these molecules continue to diffuse and react under different conditions within the gradients.

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day ⁻¹ in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml ⁻¹ ; interquartile range [IQR], 0.60 to 1.50 ng ml ⁻¹ ) and tenofovir (TFV; median, 15.0 ng ml ⁻¹ ; IQR, 8.8 to 23.3 ng ml ⁻¹ ), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10 ⁶ cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations.

Carbon dioxide is an appealing renewable feedstock for industrial chemical processes. This does not mean, however, that all chemical processes using CO₂ are environmentally-friendly. Perspectives on the sustainability of CO₂ utilization and artificial photosynthesis are provided. The discussions focus on the photocatalytic production of C_x (x ≥ 2) compounds, where all the carbon in the products is derived from CO₂ . This area of research, while promising, has received far less attention than analogous systems leading to C₁ products.

Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection “pod IVR” platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ± 335 μg day ⁻¹ (ACV) and 321 ± 207 μg day ⁻¹ (TFV); sheep, 174 ± 14 μg day ⁻¹ (ACV) and 185 ± 34 μg day ⁻¹ (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ± 7.31 μg ml ⁻¹ (ACV) and 20.6 ± 16.2 μg ml ⁻¹ (TFV); cervicovaginal lavage fluid, 118 ± 113 ng ml ⁻¹ (ACV) and 191 ± 125 ng ml ⁻¹ (TFV); tissue, 173 ng g ⁻¹ (ACV) and 93 ng g ⁻¹ (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens.