Crystalline silica polymorph surfaces and nearly free silanols: occurrence and possible role in toxicity mechanisms 

<p>Crystalline silica (CS) is a well-known toxic particle that may cause severe pathologies including silicosis, lung cancer, and several autoimmune diseases. [1a,b] The hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry.[1c] In particular, a specific family of surface silanols, called nearly free silanols (NFS), has been recently related to the interaction mechanisms occurring between quartz particles and cell membrane components, which initiate the lung inflammatory reaction. [2] Even though this phenomenon has been studied for decades on quartz, &#160;the research on other silica polymorphs was limited, also because of the relative low abundance of some polymorphs. The CS polymorphs, i.e., quartz, cristobalite, tridymite, coesite, and stishovite, share the SiO₂ stoichiometry and differentiate for crystal structure. [3] Thus, the different crystal lattices expose differently ordered hydroxyl group patterns at the crystal surface. We proved that the NFS occur and take part in the molecular bio-interactions, not only on quartz, but also on the other CS polymorphs. Five high-purity samples representative of the five CS polymorphs were fully characterized by XRPD, Scanning Electron Microscopy, and IR spectroscopy. When CS polymorphs were contacted with model membranes (red blood cells), all of them were able to disrupt cell membranes, except stishovite, which was the only polymorph without NFS. By thermally modulating the topochemistry of surface silanols, it was possible to show that the membranolytic activity of the CS polymorphs quantitatively paralleled the occurrence of NFS. This observations confirmed the central role of NFS in regulating the interaction of silica with biomembranes. In conclusion, these results put the surface characteristics of CS particles in the foreground with respect to the crystal habit and provide a comprehensive understanding of the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena. [4]</p> <p>[1] a) KAWASAKI, H. 2015, <em>Inhal Toxicol, </em>27<strong>,</strong> 363-77; b) IARC 2012, <em>IARC monographs on the evaluation of carcinogenic risks to humans, </em>Lyon, World Health 543 Organisation c). BORM, P. J. A., et al. 2018, <em>Part. Fibre. Toxicol., </em>15<strong>, </strong>23;</p> <p>[2] PAVAN, C., et al., 2020, <em>Proc Natl Acad Sci U S A, </em>117<strong>, </strong>27836-27846.</p> <p>[3] GUTHRIE, G. D. & HEANEY, P. J. 1995, <em>Scand J Work Environ Health, </em>21 Suppl 2<strong>, </strong>5-8.</p> <p>[4] PAVAN. C., et al., 2023, accepted on <em>Frontiers in Chemistry</em>, DOI: 10.3389/fchem.2022.1092221.</p>