Metal–organic frameworks (MOFs) are a unique class of crystalline solids comprised of metal cations (or metal clusters) and organic ligands that have shown promise for a wide variety of applications Over the past 15 years, research and development of these materials have become one of the most intensely and extensively pursued areas A very interesting and well-investigated topic is their optical emission properties and related applications Several reviews have provided a comprehensive overview covering many aspects of the subject up to 2011 This review intends to provide an update of work published since then and focuses on the photoluminescence (PL) properties of MOFs and their possible utility in chemical and biological sensing and detection The spectrum of this review includes the origin of luminescence in MOFs, the advantages of luminescent MOF (LMOF) based sensors, general strategies in designing sensory materials, and examples of various applications in sensing and detection

Luminescent metal–organic frameworks for chemical sensing and explosive detection

Metal–organic frameworks (MOFs) or porous coordination polymers (PCPs) are open, crystalline supramolecular coordination architectures with porous facets. These chemically tailorable framework materials are the subject of intense and expansive research, and are particularly relevant in the fields of sensory materials and device engineering. As the subfield of MOF-based sensing has developed, many diverse chemical functionalities have been carefully and rationally implanted into the coordination nanospace of MOF materials. MOFs with widely varied fluorometric sensing properties have been developed using the design principles of crystal engineering and structure–property correlations, resulting in a large and rapidly growing body of literature. This work has led to advancements in a number of crucial sensing domains, including biomolecules, environmental toxins, explosives, ionic species, and many others. Furthermore, new classes of MOF sensory materials utilizing advanced signal transduction by devices based on MOF photonic crystals and thin films have been developed. This comprehensive review summarizes the topical developments in the field of luminescent MOF and MOF-based photonic crystals/thin film sensory materials.

Metal-organic frameworks: functional luminescent and photonic materials for sensing applications.

The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclea...

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow.

The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24

Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”.

1.1. The Language Used To Describe Molecular Machines
Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14

The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14

Artificial Molecular Machines

Luminescent sensors based on metal-organic frameworks

The single-atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordination of single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H2 O2 to . OH through a Fenton-like reaction; it also promotes the decomposition of H2 O2 to O2 and continuously catalyzes the conversion of O2 to cytotoxic . O2 - via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

Stimuli-Responsive Manganese Single-Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

Platinum-based anticancer drugs are widely used in the clinic for the treatment of a broad spectrum of human malignancies. These drugs are administered to 40–80% of all patients undergoing cancer chemotherapy, either as single agents or in combination with other agents. However, their application is limited by the presence of side effects and drug resistance. Although some tumors are intrinsically resistant to platinumbased drugs, other tumors acquire resistance only after initial treatment. The sensitivity of cells toward platinum-based drugs, such as cisplatin, is dependent on DNA platination because DNA is the ultimate drug target of cisplatin. Tumor cells can acquire cisplatin resistance, that is, can achieve a reduction in the level of DNA platination, through several mechanisms, for example, through reduced drug uptake, through drug deactivation in cells, through DNA repair, and through increased drug efflux. Several cellular processes can be associated with sensitivity of cells toward cisplatin. The uptake of cisplatin into cells is facilitated by the copper transport protein (Ctr1), which is expressed in low levels in some cisplatin-resistant cells. Metallothionein (MT) is a thiol-rich protein that binds strongly to many heavy-metal ions, including platinum(II). MT plays a role in cellular detoxification by sequestering these heavy-metal compounds, and an increased concentration of this protein in cells is associated with low efficacy of cisplatin. The small peptide glutathione (GSH), which also has high affinity toward cisplatin and is found in increased concentrations in some cisplatin-resistant cells, can play a similar role. Additionally, DNA repair proteins (such as NER) and efflux proteins (such as P-type ATPases) can also reduce the efficacy of cisplatin and contribute to cisplatin resistance. To avoid the problems of resistance associated with the use of cisplatin, several types of nonclassical platinum complexes have been developed, including trans-coordinated complexes, polynuclear platinum complexes, and platinum(IV) complexes. These platinum complexes differ from cisplatin in their uptake pathway, their reactivity toward cellular proteins, and their DNA binding modes. Because of these differences, some of these nonclassical platinum complexes, such as trans-EE, BBR3464, and satraplatin, have shown promising activity in cisplatin-resistant cells. These findings suggest that the design of platinum-based drugs that have different responses to cellular processes is a feasible approach toward circumventing the problems of resistance that affect the use of cisplatin. Drug delivery systems have drawn particular attention in recent years because they can facilitate the delivery of platinum-based drugs, thus enhancing drug efficacy. A number of drug delivery systems have been developed for the delivery of platinum-based drugs. These systems have been based on polymers, solid lipids, and inorganic nanoparticles; the latter can be further subdivided into magnetic iron oxide, single-walled carbon nanotubes, metallofullerene nanoparticles, gold nanoparticles, nanoscale metal-organic frameworks, and mesoporous silica microparticles. [17] Some of these systems have entered clinical trials. With the conjugation of biologically active molecules, some delivery systems have shown high selectivity in targeting tumor cells. Although the use of drug-delivery systems has been successful in improving the efficacy of platinum-based drugs, it remains a challenge to develop drug conjugates that combat drug resistances. We have previously reported that PEGylated gold nanorods (PEG-GNRs) can facilitate the delivery of platinum(IV) prodrugs and significantly enhance the cytotoxicity of these prodrugs in tumor cells. Herein, we report that the use of this drug-delivery system avoids the drug resistance that affects the use of cisplatin. We show that impaired drug uptake that results from the low expression of Ctr1 in the cisplatin-resistant cells A549R can be overcome by using a conjugate of a cisplatin prodrug and PEGylated gold nanorods (Pt-PEG-GNRs conjugate); this conjugate facilitates the delivery of the platinum-based drug into cells through endocytosis. Additionally, the platinum(IV) prodrug is less susceptible to deactivation by the detoxification protein MT and the peptide GSH, which were found in high concentrations in A549R cells. Consequently, the Pt-PEGGNRs conjugate was highly cytotoxic to tumor cells, especially cisplatin-resistant cells. [*] Y. Min, S. Chen, G. Ma, Prof. Y. Liu CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry University of Science and Technology of China Hefei, Anhui, 230026 (China) E-mail: liuyz@ustc.edu.cn

Combating the Drug Resistance of Cisplatin Using a Platinum Prodrug Based Delivery System

The ligation of aspirin to cisplatin demonstrates significant synergistic effects on tumor cells

Rationally designed PIC nanoparticles as next-generation delivery system: we have developed a core-shell-corona PIC nanoparticle (⊕) NP/Pt@PPC-DA as a next-generation delivery system. (⊕) NP/Pt@PPC-DA exhibits prolonged circulation and enhanced drug accumulation in tumors. Subsequently, tumor pH leads to the release of (⊕) NP/Pt, which facilitates cellular uptake followed by rapid intracellular cisplatin release. Using this delivery strategy cisplatin-resistant tumor growth in a murine xenograft model has been successfully suppressed.

Rational design of polyion complex nanoparticles to overcome cisplatin resistance in cancer therapy.

http://staff.ustc.edu.cn/~jlyu/PDF/2009%20A%20numerical%20study%20on%20the%20rate%20sensitivity%20of%20cellular%20metals.pdf

Yangzhong Liu

Papers

Stimuli-Responsive Manganese Single-Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

Combating the Drug Resistance of Cisplatin Using a Platinum Prodrug Based Delivery System

The ligation of aspirin to cisplatin demonstrates significant synergistic effects on tumor cells

Rational design of polyion complex nanoparticles to overcome cisplatin resistance in cancer therapy.

A numerical study on the rate sensitivity of cellular metals