ACS Central Science最新文献

The applied physicist discusses how the layout of ancient mammoth DNA revealed the animal’s biology.

Spin-lattice relaxation constitutes a key challenge for the development of quantum technologies, as it destroys superpositions in molecular quantum bits (qubits) and magnetic memory in single molecule magnets (SMMs). Gaining mechanistic insight into the spin relaxation process has proven challenging owing to a lack of spectroscopic observables and contradictions among theoretical models. Here, we use pulse electron paramagnetic resonance (EPR) to profile changes in spin relaxation rates (T ₁) as a function of both temperature and magnetic field orientation, forming a two-dimensional data matrix. For randomly oriented powder samples, spin relaxation anisotropy changes dramatically with temperature, delineating multiple regimes of relaxation processes for each Cu(II) molecule studied. We show that traditional T ₁ fitting approaches cannot reliably extract this information. Single-crystal T ₁ anisotropy experiments reveal a surprising change in spin relaxation symmetry between these two regimes. We interpret this switch through the concept of a spin relaxation tensor, enabling discrimination between delocalized lattice phonons and localized molecular vibrations in the two relaxation regimes. Variable-temperature T ₁ anisotropy thus provides a unique spectroscopic method to interrogate the character of nuclear motions causing spin relaxation and the loss of quantum information.

Solid-state DNA origami registers, integrating liquid-phase DNA circuits, enable faster, scalable, and reliable molecular computations.

DNA computing leverages molecular reactions to achieve diverse information processing functions. Recently developed DNA origami registers, which could be integrated with DNA computing circuits, allow signal transmission between these circuits, enabling DNA circuits to perform complex tasks in a sequential manner, thereby enhancing the programming space and compatibility with various biomolecules of DNA computing. However, these registers support only single-write operations, and the signal transfer involves cumbersome and time-consuming register movements, limiting the speed of sequential computing. Here, we designed a solid-state DNA origami register that compresses output data from a 3D solution to a 2D surface, establishing a rewritable register suitable for solid-state storage. We developed a heterogeneous integration architecture of liquid-state circuits and solid-state registers, reducing the register-mediated signal transfer time between circuits to less than 1 h, thereby achieving fast sequential DNA computing. Furthermore, we designed a trace signal amplifier to read surface-stored signals back into solution. This compact approach not only enhances the speed of sequential DNA computing but also lays the foundation for the visual debugging and automated execution of DNA molecular algorithms.

This work developed a solid-state DNA origami register, with which a heterogeneous integration architecture is established and high-speed sequential DNA computing is demonstrated.

A new cyclodextrin derivative, Subetadex-α-methyl, holds promise as a medical countermeasure for fentanyl and related opioid overdoses.

The blood–brain barrier (BBB) presents one of the main obstacles to delivering anticancer drugs in glioblastoma. Herein, we investigated the potential of a series of cyclic ruthenium-peptide conjugates as photoactivated therapy candidates for the treatment of this aggressive tumor. The three compounds studied, Ru-p(HH), Ru-p(MH), and Ru-p(MM) ([Ru(Ph₂phen)₂(Ac-X₁RGDX₂-NH₂)]Cl₂ with Ph₂phen = 4,7-diphenyl-1,10-phenanthroline and X₁, X₂ = His or Met), include an integrin-targeted pentapeptide coordinated to a ruthenium warhead via two photoactivated ruthenium–X_1,2 bonds. Their photochemistry, activation mechanism, tumor targeting, and antitumor activity were meticulously addressed. A combined in vitro and in vivo study revealed that the photoactivated cell-killing mechanism and their O₂ dependence were strongly influenced by the nature of X₁ and X₂. Ru-p(MM) was shown to be a photoactivated chemotherapy (PACT) drug, while Ru-p(HH) behaved as a photodynamic therapy (PDT) drug. All conjugates, however, showed comparable antitumor targeting and efficacy toward human glioblastoma 3D spheroids and orthotopic glioblastoma tumor models in zebrafish embryos. Most importantly, in this model, all three compounds could effectively cross the BBB, resulting in excellent targeting of the tumors in the brain.

We show the excellent blood−brain barrier crossing properties, tumor targeting, and antitumor activity of three cyclic ruthenium-peptide phototherapeutic conjugates for the treatment of glioblastoma.

The blood-brain barrier (BBB) presents one of the main obstacles to delivering anticancer drugs in glioblastoma. Herein, we investigated the potential of a series of cyclic ruthenium-peptide conjugates as photoactivated therapy candidates for the treatment of this aggressive tumor. The three compounds studied, Ru-p(HH), Ru-p(MH), and Ru-p(MM) ([Ru(Ph₂phen)₂ (Ac-X₁RGDX₂-NH₂)]Cl₂ with Ph₂phen = 4,7-diphenyl-1,10-phenanthroline and X₁, X₂ = His or Met), include an integrin-targeted pentapeptide coordinated to a ruthenium warhead via two photoactivated ruthenium-X_1,2 bonds. Their photochemistry, activation mechanism, tumor targeting, and antitumor activity were meticulously addressed. A combined in vitro and in vivo study revealed that the photoactivated cell-killing mechanism and their O₂ dependence were strongly influenced by the nature of X₁ and X₂. Ru-p(MM) was shown to be a photoactivated chemotherapy (PACT) drug, while Ru-p(HH) behaved as a photodynamic therapy (PDT) drug. All conjugates, however, showed comparable antitumor targeting and efficacy toward human glioblastoma 3D spheroids and orthotopic glioblastoma tumor models in zebrafish embryos. Most importantly, in this model, all three compounds could effectively cross the BBB, resulting in excellent targeting of the tumors in the brain.