Expanding limits of artificial enzymes: unprecedented catalysis by an oxidase nanozyme in activating a structural protein for covalent crosslinking and conferring remarkable proteolytic resistance.

Nature has endowed us with some complex enzymes capable of utilizing proteins as their substrates to generate functional proteins through post-translational modification. However, nanozymes' interplay with proteins as substrates is scarce, with their chemistry predominantly established using only small molecule substrates, featuring a significant gap in this area. Due to the huge prospects of nanozymes in biotechnological and therapeutic interventions, studies establishing the unexplored roles of nanozymes in the biological environments and their interplay beyond small molecule substrates warrant immediate attention. In this study, we unveil the unprecedented role of a Mn-based oxidase nanozyme (MnN) in activating a structural protein, collagen, and covalently crosslinking its tyrosine residues with only a trace amount of tannic acid (TA) without compromising its triple-helical structural integrity. While therapeutic applications demand materials prepared from collagen, the current chemical and physical crosslinking of collagen often presents significant challenges such as toxicity, denaturation, or high costs. MnN lucidly accomplishes crosslinking interplay at its 101 facets using oxygen as a co-substrate under mild conditions. This process takes advantage of MnN being active at mild acidic pH where collagen preferentially exists as a soluble triple helix (monomeric form), exposing functionalities and enhancing the crosslinking degree. Importantly, this reaction also confers 100% resistance to collagenase attack on the collagen tendon-derived biological material. The catalyzed TA-tyrosine linkage in the telopeptide region of collagen probably impedes the initial recognition step of collagenase, providing robust protection against its degradative action. Our study not only expands the repertoire of nanozymes' substrates beyond the existing library of small molecules but also establishes a significant step toward designing a gold standard for collagen crosslinking. With biomedical applications demanding biomaterials derived from protein scaffolds with preserved structural integrity, our investigation bridges the gap between nanozymes' chemistry and crosslinking proteins, opening exciting prospects for biomaterial development.

Approach of a small protein to the biomimetic bis-(µ-oxo) dicopper active-site installed in MOF-808 pores with restricted access perturbs substrate selectivity of oxidase nanozyme.

Advances in nanozymes have taken shape over the past few years in several domains. However, persisting challenging limitations of selectivity, specificity, and efficiency necessitate careful attention to aid in the development of next-generation artificial enzymes. Despite nanozymes having significant therapeutic and biotechnological prospects, the multienzyme mimetic activities can compromise their intended applications. Furthermore, the lack of substrate selectivity can hamper crucial biological pathways. While working on addressing the challenges of nanozymes, in this work, we aim to highlight the interplay between the substrates and bis-(µ-oxo) dicopper active site-installed MOF-808 for selectively mimicking oxidase. This oxidase mimetic with a small pore-aperture (1.4 nm), similar to the opening of enzyme binding pockets, projects a tight control over the dynamics and the reactivity of substrates, making it distinct from the general oxidase nanozymes. Interestingly, the design and the well-regulated activity of this nanozyme effectively thwart DNA from approaching the active site, thereby preventing its oxidative damage. Crucially, we also show that despite these merits, the oxidase selectivity is compromised by small proteins such as cytochrome c (Cyt c), having dimensions larger than the pore aperture of MOF-808. This reaction lucidly produces water molecules as a result of four electron transfer to an oxygen molecule. Such unintended side reactivities warrant special attention as they can perturb redox processes and several cellular energy pathways. Through this study, we provide a close look at designing next-generation artificial enzymes that can address the complex challenges for their utility in advanced applications.

Advances in nanotechnology application in biosafety materials: A crucial response to COVID-19 pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has adversely affected the public domain causing unprecedented cases and high mortality across the globe. This has brought back the concept of biosafety into the spotlight to solve biosafety problems in developing diagnostics and therapeutics to treat COVID-19. The advances in nanotechnology and material science in combination with medicinal chemistry have provided a new perspective to overcome this crisis. Herein, we discuss the efforts of researchers in the field of material science in developing personal protective equipment (PPE), detection devices, vaccines, drug delivery systems, and medical equipment. Such a synergistic approach of disciplines can strengthen the research to develop biosafety products in solving biosafety problems.

A Review on the Role of Transition Metals in Selenylation Reactions.

Organoselenium chemistry has emerged as a distinctive area of research with tremendous utility in the synthesis of biologically and pharmaceutically active molecules. Significant synthetic approaches have been made for the construction of C-Se bonds, which are useful in other organic transformations. This review focuses on the versatility of transition metal-mediated selenylation reactions, providing insights into various synthetic pathways and mechanistic details. Furthermore, this review aims to offer a broad perspective for designing efficient and novel catalysts to incorporate organoselenium moiety into the inert C-H bonds.