A Facile Synthesis and Structural Verification of Etorphine and Dihydroetorphine from Codeine

In this study, an improved process for the synthesis of etorphine and dihydroetorphine from codeine with an overall yield of 2.7% and 1.5% respectively is described. The structure of 19‐propylthevinol 7 was verfied by X‐ray structure analysis. This result is promising for synthesizing various morphine‐based drugs.     

Polypeptides with High Zwitterion Density for Safe and Effective Therapeutics

The commonly used “stealth material” poly(ethylene glycol) (PEG) effectively promotes the pharmacokinetics of therapeutic cargos while reducing their immune response. However, recent studies have suggested that PEG could induce adverse reactions, including the emergence of anti‐PEG antibodies and tissue histologic changes. An alternative stealth material with no or less immunogenicity and organ toxicity is thus urgently needed. We designed a polypeptide with high zwitterion density (PepCB) as a stealth material for therapeutics. Neither tissue histological changes in liver, kidney, or spleen, nor abnormal behavior, sickness or death was induced by the synthesized polymer after high‐dosage administration for three months in rats. When conjugated to a therapeutic protein uricase, the uricase–PepCB bioconjugate showed significantly improved pharmacokinetics and immunological properties compared with uricase–PEG conjugates.     

Quantum Thermodynamic Uncertainty Relations,Generalized Current Fluctuations and Nonequilibrium Fluctuation–Dissipation Inequalities

Thermodynamic uncertainty relations (TURs) represent one of the few broad-based and fundamental relations in our toolbox for tackling the thermodynamics of nonequilibrium systems. One form of TUR quantifies the minimal energetic cost of achieving a certain precision in determining a nonequilibrium current. In this initial stage of our research program, our goal is to provide the quantum theoretical basis of TURs using microphysics models of linear open quantum systems where it is possible to obtain exact solutions. In paper [Dong et al., Entropy 2022, 24, 870], we show how TURs are rooted in the quantum uncertainty principles and the fluctuation–dissipation inequalities (FDI) under fully nonequilibrium conditions. In this paper, we shift our attention from the quantum basis to the thermal manifests. Using a microscopic model for the bath’s spectral density in quantum Brownian motion studies, we formulate a “thermal” FDI in the quantum nonequilibrium dynamics which is valid at high temperatures. This brings the quantum TURs we derive here to the classical domain and can thus be compared with some popular forms of TURs. In the thermal-energy-dominated regimes, our FDIs provide better estimates on the uncertainty of thermodynamic quantities. Our treatment includes full back-action from the environment onto the system. As a concrete example of the generalized current, we examine the energy flux or power entering the Brownian particle and find an exact expression of the corresponding current–current correlations. In so doing, we show that the statistical properties of the bath and the causality of the system+bath interaction both enter into the TURs obeyed by the thermodynamic quantities.     

Quantum Thermodynamic Uncertainties in Nonequilibrium Systems from Robertson-Schrödinger Relations

Thermodynamic uncertainty principles make up one of the few rare anchors in the largely uncharted waters of nonequilibrium systems, the fluctuation theorems being the more familiar. In this work we aim to trace the uncertainties of thermodynamic quantities in nonequilibrium systems to their quantum origins, namely, to the quantum uncertainty principles. Our results enable us to make this categorical statement: For Gaussian systems, thermodynamic functions are functionals of the Robertson-Schrödinger uncertainty function, which is always non-negative for quantum systems, but not necessarily so for classical systems. Here, quantum refers to noncommutativity of the canonical operator pairs. From the nonequilibrium free energy, we succeeded in deriving several inequalities between certain thermodynamic quantities. They assume the same forms as those in conventional thermodynamics, but these are nonequilibrium in nature and they hold for all times and at strong coupling. In addition we show that a fluctuation-dissipation inequality exists at all times in the nonequilibrium dynamics of the system. For nonequilibrium systems which relax to an equilibrium state at late times, this fluctuation-dissipation inequality leads to the Robertson-Schrödinger uncertainty principle with the help of the Cauchy-Schwarz inequality. This work provides the microscopic quantum basis to certain important thermodynamic properties of macroscopic nonequilibrium systems.