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This study explores the oxygen-binding mechanism and the potential peroxo-to-bis-μ-oxo isomerization in hemocyanin (Hc) using a quantum mechanics/molecular mechanics (QM/MM) approach at the multireference NEVPT2 level of theory (QM[NEVPT2]/MM). Our results support the previously proposed mechanism for Hc oxygen binding, involving two nearly simultaneous electron-transfer (ET) steps and a triplet-singlet intersystem crossing (ISC). However, we find that the first ET step occurs prior to ISC, resulting in the formation of a stable singlet superoxide intermediate through a low-energy barrier. The second ET leads to the formation of a singlet oxy-hemocyanin species featuring the characteristic peroxo-Cu 2 O 2 "butterfly" core. Moreover, QM[NEVPT2]/MM simulations reveal a lower-energy barrier for the peroxo-to-bis-μ-oxo isomerization compared with density functional theory (DFT), although the peroxo form remains energetically favored within the protein environment. These findings offer new insights into the behavior of the hemocyanin active site, highlighting the importance of considering both the electronic correlation and the protein environment in accurately modeling copper-oxygen interactions in biological systems.

The world obeys quantum physics and quantum computing presents an alternative way to map physical problems to systems that follow the same laws. Such computation fundamentally constitutes a better way to understand the most challenging quantum problems. One such problem is the accurate simulation of highly correlated quantum systems. Still, modern-day quantum hardware has limitations and only allows for the modeling of simple systems. Here, we present for the first time a quantum computer model simulation of a complex hemocyanin molecule, which is an important respiratory protein involved in various physiological processes and is also used as a key component in therapeutic vaccines for cancer. To characterize the mechanism by which hemocyanin transports oxygen, variational quantum eigensolver (VQE) and quantum embedding methods are used in the context of dynamic mean field theory to solve the Anderson impurity model (AIM). Finally, it is concluded that the magnetic structure of hemocyanin is largely influenced by the many-body correction and that the computational effort for solving correlated electron systems could be substantially reduced with the introduction of quantum computing algorithms. We encourage the use of the Hamiltonian systems presented in this paper as a benchmark for testing quantum computing algorithms' efficiency for chemistry applications.

Nanoparticles are increasingly being used in the development of vaccines for disease prevention or treatment. Recent research has demonstrated that conjugating a protein onto the surface of nanoparticles can significantly increase its immunogenicity. Considering various pathogens that threaten human health, multivalent vaccines are often desirable. Up to now, nanoparticle-based vaccines are mostly limited to one protein per nanoparticle. No research has been conducted to explore the possibility of conjugating more than one protein onto the surface of a nanoparticle. Here we developed a specific conjugation strategy to conjugate multiple proteins to the PLGA/lipid hybrid nanoparticle surface. The maleimide-thiol Michael addition, Aizde-DBCO (Dibenzocyclooctyne), and TCO (trans-cycloctene)-Tetrazine click chemistry were employed to conjugate three different proteins, subunit keyhole limpet hemocyanin (sKLH), Ovalbumin (OVA), and cross-reactive material 197 (CRM 197 ), to the surface of PLGA/lipid hybrid nanoparticles (hNPs). The successful results of this study pave the way for developing multivalent vaccines against different pathogens., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)