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Abstract Hematin crystallization is an essential element of heme detoxification of malaria parasites and its inhibition by antimalarial drugs is a common treatment avenue. We demonstrate at biomimetic conditions in vitro irreversible inhibition of hematin crystal growth due to distinct cooperative mechanisms that activate at high crystallization driving forces. The evolution of crystal shape after limited-time exposure to both artemisinin metabolites and quinoline-class antimalarials indicates that crystal growth remains suppressed after the artemisinin metabolites and the drugs are purged from the solution. Treating malaria parasites with the same agents reveals that three- and six-hour inhibitor pulses inhibit parasite growth with efficacy comparable to that of inhibitor exposure during the entire parasite lifetime. Time-resolved in situ atomic force microscopy (AFM), complemented by light scattering, reveals two molecular-level mechanisms of inhibitor action that prevent β-hematin growth recovery. Hematin adducts of artemisinins incite copious nucleation of nonextendable nanocrystals, which incorporate into larger growing crystals, whereas pyronaridine, a quinoline-class drug, promotes step bunches, which evolve to engender abundant dislocations. Both incorporated crystals and dislocations are known to induce lattice strain, which persists and permanently impedes crystal growth. Nucleation, step bunching, and other cooperative behaviors can be amplified or curtailed as means to control crystal sizes, size distributions, aspect ratios, and other properties essential for numerous fields that rely on crystalline materials.
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Using metal precursors to passivate oxides for area selective deposition
Although it has long been known that metal-containing compounds can serve as catalysts for chemical vapor deposition (CVD) of films from other precursors, we show that metal-containing compounds can also inhibit CVD nucleation or growth. For two precursors A and B with growth onset temperatures TgA < TgB when used independently, it is possible that B can inhibit growth from A when the two precursors are coflowed onto a substrate at a temperature (T) where TgA < T < TgB. Here, we consider three precursors: AlH3⋅NMe3 (Tg = 130 °C, Me = CH3), Hf(BH4)4 (Tg = 170 °C), and AlMe3 (Tg = 300 °C). We find that (i) nucleation of Al from AlH3⋅NMe3 is inhibited by Hf(BH4)4 at 150 °C on two oxide surfaces (Si with native oxide and borosilicate glass), (ii) nucleation and growth of HfB2 is inhibited by AlMe3 at 250 °C on native oxide substrates and on HfB2 nuclei, and (iii) nucleation of Al from AlH3⋅NMe3 is inhibited by AlMe3 at 200 °C on native oxide substrates. Inhibition by Hf(BH4)4 is transient and persists only as long as its coflow is maintained; in contrast, AlMe3 inhibition of HfB2 growth is more permanent and continues after coflow is halted. As a result of nucleation inhibition, AlMe3 coflow enhances selectivity for HfB2 deposition on Au (growth) over Al2O3 (nongrowth) surfaces, and Hf(BH4)4 coflow makes it possible to deposit Al on Al nuclei and not on the surrounding oxide substrate. We propose the following criteria to identify candidate molecules for other precursor–inhibitor combinations: (i) the potential inhibitor should have a higher Tg than the desired film precursor, (ii) the potential inhibitor should be unreactive toward the desired film precursor, and (iii) at the desired growth temperature, the potential inhibitor should adsorb strongly enough to form a saturated monolayer on the intended nongrowth surface at accessible inhibitor pressures.
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- Award ID(s):
- 1954745
- PAR ID:
- 10506042
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- Journal of Vacuum Science & Technology A
- Volume:
- 41
- Issue:
- 3
- ISSN:
- 0734-2101
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1116/6.0002413
