SVALKA-POLYCOMB REPRESSIVE COMPLEX2 module controls C-REPEAT BINDING FACTOR3 induction during cold acclimation.

C-REPEAT BINDING FACTORS (CBFs) are highly conserved plant transcription factors that promote cold tolerance. In Arabidopsis (Arabidopsis thaliana), three CBFs (CBF1 to CBF3) play a critical role in cold acclimation, and the expression of their corresponding genes is rapidly and transiently induced during this adaptive response. Cold induction of CBFs has been extensively studied and shown to be tightly controlled, yet the molecular mechanisms that restrict the expression of each CBF after their induction during cold acclimation are poorly understood. Here, we present genetic and molecular evidence that the decline in the induction of CBF3 during cold acclimation is epigenetically regulated through the Polycomb Repressive Complex (PRC) 2. We show that this complex promotes the deposition of the repressive mark H3K27me3 at the coding region of CBF3, silencing its expression. Our results indicate that the cold-inducible long noncoding RNA SVALKA is essential for this regulation by recruiting PRC2 to CBF3. These findings unveil a SVALKA-PRC2 regulatory module that ensures the precise timing of CBF3 induction during cold acclimation and the correct development of this adaptive response.

Real-world study: Impact of multidisciplinary management of apalutamide-associated adverse events in prostate cancer.

OBJECTIVE: To analyse the adverse events (AEs) associated with apalutamide and the impact of a multidisciplinary team (MDT) protocol on its management at a tertiary care hospital in a real-world setting. METHODS: This was an observational, prospective, cohort study based on real-world evidence at the Hospital Clínic de Barcelona. Includes patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC) and who started treatment with apalutamide between May 2019 and March 2023 in a real-world clinical setting. RESULTS: Of the 121 patients treated with apalutamide, 52.1% experienced an AE, 19.8% experienced temporarily interruption or a reduction in the dose of apalutamide, and 13.2% discontinued treatment due to AEs. Without MDT protocol (49 patients), 24.5% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 10.1 months, and 24.5% discontinued apalutamide due to AEs, with a median time from the start of treatment of 3.1 months. Meanwhile, whit MDT protocol (72 patients), 16.7% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 1.6 months, and 5.6% discontinued apalutamide due to AEs, with a median time from the start of treatment of 4 months. The risk reduction associated with treatment discontinuation was statistically significant (p-value = 0.003). CONCLUSIONS: This study highlights the importance of MDT management of AEs associated with apalutamide to reduce treatment discontinuation.

Isoreticular Expansion and Linker-Enabled Control of Interpenetration in Titanium-Organic Frameworks.

Titanium-organic frameworks offer distinctive opportunities in the realm of metal-organic frameworks (MOFs) due to the integration of intrinsic photoactivity or redox versatility in porous architectures with ultrahigh stability. Unfortunately, the high polarizing power of Ti4+ cations makes them prone to hydrolysis, thus preventing the systematic design of these types of frameworks. We illustrate the use of heterobimetallic cluster Ti2Ca2 as a persistent building unit compatible with the isoreticular design of titanium frameworks. The MUV-12(X) and MUV-12(Y) series can be all synthesized as single crystals by using linkers of varying functionalization and size for the formation of the nets with tailorable porosity and degree of interpenetration. Following the generalization of this approach, we also gain rational control over interpenetration in these nets by designing linkers with varying degrees of steric hindrance to eliminate stacking interactions and access the highest gravimetric surface area reported for titanium(IV) MOFs (3000 m2 g-1).

Development and Validation of Nerve-Targeted Bacteriochlorin Sensors.

We report an innovative approach to producing bacteriochlorins (bacs) via formal cycloaddition by subjecting a porphyrin to a trimolecular reaction. Bacs are near-infrared probes with the intrinsic ability to serve in multimodal imaging. However, despite their ability to fluoresce and chelate metal ions, existing bacs have thus offered limited ability to label biomolecules for target specificity or have lacked chemical purity, limiting their use in bio-imaging. In this work, bacs allowed a precise and controlled appending of clickable linkers, lending the porphyrinoids substantially more chemical stability, clickability, and solubility, rendering them more suitable for preclinical investigation. Our bac probes enable the targeted use of biomolecules in fluorescence imaging and Cerenkov luminescence for guided intraoperative imaging. Bacs' capacity for chelation provides opportunities for use in non-invasive positron emission tomography/computed tomography. Herein, we report the labeling of bacs with Hs1a, a (NaV1.7)-sodium-channel-binding peptide derived from the Chinese tarantula Cyriopagopus schmidti to yield Bac-Hs1a and radiolabeled Hs1a, which shuttles our bac sensor(s) to mouse nerves. In vivo, the bac sensor allowed us to observe high signal-to-background ratios in the nerves of animals injected with fluorescent Bac-Hs1a and radiolabeled Hs1a in all imaging modes. This study demonstrates that Bac-Hs1a and [64Cu]Cu-Bac-Hs1a accumulate in peripheral nerves, providing contrast and utility in the preclinical space. For the chemistry and bio-imaging fields, this study represents an exciting starting point for the modular manipulation of bacs, their development and use as probes for diagnosis, and their deployment as formidable multiplex nerve-imaging agents for use in routine imaging experiments.

Polydopamine Incorporation Enhances Cell Differentiation and Antibacterial Properties of 3D-Printed Guanosine-Borate Hydrogels for Functional Tissue Regeneration.

Tissue engineering focuses on the development of materials as biosubstitutes that can be used to regenerate, repair, or replace damaged tissues. Alongside this, 3D printing has emerged as a promising technique for producing implants tailored to specific defects, which in turn increased the demand for new inks and bioinks. Especially supramolecular hydrogels based on nucleosides such as guanosine have gained increasing attention due to their biocompatibility, good mechanical characteristics, tunable and reversible properties, and intrinsic self-healing capabilities. However, most existing formulations exhibit insufficient stability, biological activity, or printability. To address these limitations, we incorporated polydopamine (PDA) into guanosine-borate (GB) hydrogels and developed a PGB hydrogel with maximal PDA incorporation and good thixotropic and printability qualities. The resulting PGB hydrogels exhibited a well-defined nanofibrillar network, and we found that PDA incorporation increased the hydrogel's osteogenic activity while having no negative effect on mammalian cell survival or migration. In contrast, antimicrobial activity was observed against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Thus, our findings suggest that our PGB hydrogel represents a significantly improved candidate as a 3D-printed scaffold capable of sustaining living cells, which may be further functionalized by incorporating other bioactive molecules for enhanced tissue integration.

Osteoblastic Cell Behavior and Gene Expression Related to Bone Metabolism on Different Titanium Surfaces.

The surface topography of titanium dental implants has a great influence on osseointegration. In this work, we try to determine the osteoblastic behavior and gene expression of cells with different titanium surfaces and relate them to the physicochemical properties of the surface. For this purpose, we have used commercial titanium discs of grade 3: as-received corresponds to machined titanium without any surface treatment (MA), chemically acid etched (AE), treated via sand blasting with Al2O3 particles (SB) and a sand-blasting treatment with acid etching (SB+AE). The surfaces have been observed using scanning electron microscopy (SEM) and the roughness, wettability and surface energy with dispersive and polar components have been characterized. Osteoblastic cultures were performed with SaOS-2 osteoblastic cells determining cell viability as well as alkaline phosphatase levels for 3 and 21 days, and osteoblastic gene expression was determined. The roughness values of the MA discs was 0.02 µm, which increases to 0.3 µm with acid attack and becomes the maximum for the sand-blasted samples, reaching values of 1.2 µm for SB and SB+AE. The hydrophilic behavior of the MA and AE samples with contact angles of 63° and 65° is superior to that of the rougher samples, being 75° for SB and 82° for SB+AE. In all cases, they show good hydrophilicity. GB and GB+AE surfaces present a higher polar component in the surface energy values, 11.96 and 13.18 mJ/m2, respectively, than AE and MA, 6.64 and 9.79 mJ/m2, respectively. The osteoblastic cell viability values at three days do not show statistically significant differences between the four surfaces. However, the viability of the SB and SB+AE surfaces at 21 days is much higher than that of the AE and MA samples. From the alkaline phosphatase studies, higher values were observed for those treated with sand blasting with and without acid etching compared to the other two surfaces, indicating a greater activity in osteoblastic differentiation. In all cases except in the Osterix (Ostx) -osteoblast-specific transcription factor-a decrease in gene expression is observed in relation to the MA samples (control). The most important increase was observed for the SB+AE condition. A decrease in the gene expression of Osteoprotegerine (OPG), Runt-related transcription factor 2 (Runx2), Receptor Activator of NF-κB Ligand (RANKL) and Alkaline Phosphatase (Alp) genes was observed in the AE surface.

A Crystalline 1D Dynamic Covalent Polymer.

The synthesis of crystalline one-dimensional polymers provides a fundamental understanding about the structure-property relationship in polymeric materials and allows the preparation of materials with enhanced thermal, mechanical, and conducting properties. However, the synthesis of crystalline one-dimensional polymers remains a challenge because polymers tend to adopt amorphous or semicrystalline phases. Herein, we report the synthesis of a crystalline one-dimensional polymer in solution by dynamic covalent chemistry. The structure of the polymer has been unambiguously confirmed by microcrystal electron diffraction that together with charge transport studies and theoretical calculations show how the π-stacked chains of the polymer generate optimal channels for charge transport.

A MRG-operated chromatin switch at SOC1 attenuates abiotic stress responses during the floral transition.

Plants react to environmental challenges by integrating external cues with endogenous signals to optimize survival and reproductive success. However, the mechanisms underlying this integration remain obscure. While stress conditions are known to impact plant development, how developmental transitions influence responses to adverse conditions has not been addressed. Here, we reveal a molecular mechanism of stress response attenuation during the onset of flowering in Arabidopsis (Arabidopsis thaliana). We show that Arabidopsis MORF-RELATED GENE (MRG) proteins, components of the NuA4 histone acetyltransferase complex that bind trimethylated-lysine 36 in histone H3 (H3K36me3), function as a chromatin switch on the floral integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) to coordinate flowering initiation with plant responsiveness to hostile environments. MRG proteins are required to activate SOC1 expression during flowering induction by promoting histone H4 acetylation. In turn, SOC1 represses a broad array of genes that mediate abiotic stress responses. We propose that during the transition from vegetative to reproductive growth, the MRG-SOC1 module constitutes a central hub in a mechanism that tunes down stress responses to enhance the reproductive success and plant fitness at the expense of costly efforts for adaptation to challenging environments.

High-power UTC-photodiodes for an optically pumped subharmonic terahertz receiver.

In this work, we present an optically subharmonic pumped WR3-mixer for enabling photonic coherent frequency-domain terahertz (THz) imaging and spectroscopy systems in the future. The studied mixer operates within the upper range of the WR3-band from 270 GHz to 320 GHz. High-power uni-travelling carrier photodiodes (UTC-PDs) are developed for providing the subharmonic local oscillator (LO) signal within the corresponding WR6-band in the range between 135 GHz and 160 GHz. The proposed THz mixer module consists of a gallium arsenide (GaAs)-based low barrier Schottky diodes (LBSDs) chip and an indium phosphide (InP)-based UTC-PD chip. For integrating the UTC-PD with the WR6 at the mixer's LO input, an E-plane transition and a stepped-impedance microstrip line low pass filter (MSL-LPF) are developed and monolithically integrated with the UTC-PD chip on a 100 µm thick InP substrate. The E-plane transition converts the quasi-TEM mode of the grounded coplanar waveguide (GCPW) to the dominant TE10 mode of the WR6 and matches the GCPW's impedance with the WR6's impedance. According to full-wave EM simulations, the transition exhibits a 1 dB bandwidth (BW) of more than 30 GHz (138.8-172.1 GHz) with a corresponding return loss (RL) better than 10 dB, whereas the minimum insertion loss (IL) is 0.65 dB at a frequency of 150 GHz. Experimentally, the 1 dB BW of the fabricated transition is found to be between 140 GHz and 170 GHz, which confirms the numerical results. The minimum measured IL is 2.94 dB, i.e., about 2 dB larger than the simulated value. In order to achieve the required LO power for successfully pumping the mixer in a direct approach (i.e., without an additional LO amplifier), the design of the epitaxial system of the UTC-PD is optimized to provide a high output power within the WR6-band (110-170 GHz). Experimentally, at 150 GHz, the output power of the fabricated UTC-PD chip is measured to be +3.38 dBm at a photocurrent of 21 mA. To our knowledge, this is the highest output power ever achieved from a UTC-PD at 150 GHz. Finally, the developed high-power UTC-PDs are used as LO source to pump the subharmonic WR3-mixer. Experimentally, the conversion loss (CL) is determined in dependency of the LO power levels within the RF frequency range between 271 GHz and 321 GHz for a fixed IF at 1 GHz. The achieved results have revealed an inverse relation between the CL and LO power level, where the average minimum CL of 16.8 dB is achieved at the highest applied LO power level, corresponding to a photocurrent of 10 mA. This CL figure is promising and is expected to reach the CL of electronically pumped and commercially available THz mixers (∼12 dB) after packaging the LO source with the mixer. Furthermore, an average CL of 17.2 dB is measured at a fixed LO frequency of 150 GHz and a tuned RF frequency between 301 GHz and 310 GHz, i.e., IF between 1 GHz and 10 GHz.

Effect of the Size of Titanium Particles Released from Dental Implants on Immunological Response.

The techniques used in oral implantology to remove bacterial biofilm from the surface of implants by machining the titanium surface (implantoplasty) or by placing rough dental implants through friction with the cortical bone generate a large release of particles. In this work, we performed a simulation of particle generation following clinical protocols. The particles were characterized for commercially pure titanium with particle sizes of 5, 10, 15, and 30 µm. The aim was to determine the effect of particle size and chemical composition of the implant on the immune response. For this purpose, their morphology and possible contamination were characterized by scanning electron microscopy and X-ray microanalysis. In addition, the granulometry, specific surface area, release of metal ions into the medium, and studies of cytocompatibility, gene expression, and cytokine release linked to the inflammatory process were studied. The release of ions for titanium particles showed levels below 800 ppb for all sizes. Smaller particle sizes showed less cytotoxicity, although particles of 15 µm presented higher levels of cytocompatibility. In addition, inflammatory markers (TNFα and Il-1ß) were higher compared to larger titanium. Specifically, particles of 15 µm presented a lower proinflammatory and higher anti-inflammatory response as characterized by gene expression and cytokine release, compared to control or smaller particles. Therefore, in general, there is a greater tendency for smaller particles to produce greater toxicity and a greater proinflammatory response.

On-Growth and In-Growth Osseointegration Enhancement in PM Porous Ti-Scaffolds by Two Different Bioactivation Strategies: Alkali Thermochemical Treatment and RGD Peptide Coating.

A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a bioactive surface is needed to stimulate implant osteointegration and improve mechanical stability. In this study, porous titanium implants were produced via powder sintering to create different porous diameters and open interconnectivity. Two strategies were used to generate a bioactive surface on the metallic foams: (1) an inorganic alkali thermochemical treatment, (2) grafting a cell adhesive tripeptide (RGD). RGD peptides exhibit an affinity for integrins expressed by osteoblasts, and have been reported to improve osteoblast adhesion, whereas the thermochemical treatment is known to improve titanium implant osseointegration upon implantation. Bioactivated scaffolds and control samples were implanted into the tibiae of rabbits to analyze the effect of these two strategies in vivo regarding bone tissue regeneration through interconnected porosity. Histomorphometric evaluation was performed at 4 and 12 weeks after implantation. Bone-to-implant contact (BIC) and bone in-growth and on-growth were evaluated in different regions of interest (ROIs) inside and outside the implant. The results of this study show that after a long-term postoperative period, the RGD-coated samples presented higher quantification values of quantified newly formed bone tissue in the implant's outer area. However, the total analyzed bone in-growth was observed to be slightly greater in the scaffolds treated with alkali thermochemical treatment. These results suggest that both strategies contribute to enhancing porous metallic implant stability and osteointegration, and a combination of both strategies might be worth pursuing.

Effects of Massage and Cold Water Immersion After an Exhaustive Run on Running Economy and Biomechanics: A Randomized Controlled Trial.

ABSTRACT: Duñabeitia, I, Arrieta, H, Rodriguez-Larrad, A, Gil, J, Esain, I, Gil, SM, Irazusta, J, and Bidaurrazaga-Letona, I. Effects of massage and cold water immersion after an exhaustive run on running economy and biomechanics: A randomized controlled trial. J Strength Cond Res 36(1): 149-155, 2022-This study compares the effects of 2 common recovery interventions performed shortly after an exhausting interval running session on running economy (RE) and biomechanics. Forty-eight well-trained male runners performed an exhaustive interval running protocol and an incremental treadmill test 24 hours later at 3 speeds: 12, 14, and 16 km·h-1. Subjects randomly received either massage, cold water immersion (CWI), or passive rest (control). Runners repeated the treadmill test 48 hours after the first test. A two-way mixed analysis of variance was performed comparing groups and testing times. The massage group had significantly better recovery than the control group at 14 km·h-1 in RE (p < 0.05; η2 = 0.176) and greater stride height and angle changes at 16 km·h-1 (p < 0.05; η2 = 0.166 and p < 0.05; η2 = 0.208, respectively). No differences were observed between the CWI and control groups. The massage group had greater stride height and angle changes at 16 km·h-1 than the CWI group (p < 0.05; η2 = 0.139 and p < 0.05; η2 = 0.168, respectively). Moreover, differences in magnitude suggested moderate effects on RE (η2 = 0.076) and swing time (η2 = 0.110). These results suggest that massage intervention promotes faster recovery of RE and running biomechanics than CWI or passive rest.

Effects of an individualized and progressive multicomponent exercise program on blood pressure, cardiorespiratory fitness, and body composition in long-term care residents: Randomized controlled trial.

This study analyzed the effects of an individualized and progressive multicomponent exercise program on blood pressure, cardiorespiratory fitness, and body composition in long-term care residents. This was a single-blind, multicenter, randomized controlled trial performed in 10 long-term care settings and involved 112 participants. Participants were randomly assigned to a control group or an intervention group. The control group participated in routine activities; the intervention group participated in a six-month individualized and progressive multicomponent exercise program focused on strength, balance, and walking recommendations. The intervention group maintained peak VO2, oxygen saturation, and resting heart rate, while the control group showed a significant decrease in peak VO2 and oxygen saturation and an increase in resting heart rate throughout the six-month period. Individualized and progressive multicomponent exercise programs comprising strength, balance, and walking recommendations appear to be effective in preventing cardiorespiratory fitness decline in older adults living in long-term care settings.

A FEMALE CASE OF SPINOCEREBELLAR ATAXIA TYPE 10 WITH SUICIDAL BEHAVIOR AND ENDOCRINPATHIES ASSOCIATED WITH A MASSIVE EXPANSION (ATTCT) OF THE GENE ATXN10.

Spinocerebellar ataxia type 10 (SCA10) is characteri- zed by ataxia, psychiatric disorders convulsions, and locus at 22q13.311. It is caused by expansions between 800-4500 pentanucleotide ATTCT repeats in intron 9 of the ATXN10 gene1-2. The ATXN10 gene encodes ataxin-10 protein (known as E46L) involved in neuritogenesis 1. SCA10 has a founder origin in Mexican, Brazilian, Argentine populattons but is rare in others.

Permanent Porosity in Hydroxamate Titanium-Organic Polyhedra.

Following the synthesis of hydroxamate titanium-organic frameworks, we now extend these siderophore-type linkers to the assembly of the first titanium-organic polyhedra displaying permanent porosity. Mixed-linker versions of this molecular cage (cMUV-11) are also used to demonstrate the effect of pore chemistry in accessing high surface areas of near 1200 m2·g-1.

Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers.

Almost 17 million Americans have a history of cancer, a number expected to reach over 22 million by 2030. Cancer patients often undergo chemotherapy in the form of antineoplastic agents such as cis-platin and paclitaxel. Though effective, these agents can induce debilitating side effects; the most common neurotoxic effect, chemotherapy-induced peripheral neuropathy (CIPN), can endure long after treatment ends. Despite the widespread and chronic nature of the dysfunction, no tools exist to quantitatively measure chemotherapy-induced peripheral neuropathy. Such a tool would not only benefit patients but their stratification could also save significant financial and social costs associated with neuropathic pain. In our first step toward addressing this unmet clinical need, we explored a novel dual approach to localize peripheral nerves: Cerenkov luminescence imaging (CLI) and fluorescence imaging (FI). Our approach revolves around the targeting and imaging of voltage-gated sodium channel subtype NaV1.7, highly expressed in peripheral nerves from both harvested human and mouse tissues. For the first time, we show that Hsp1a, a radiolabeled NaV1.7-selective peptide isolated from Homoeomma spec. Peru, can serve as a targeted vector for delivering a radioactive sensor to the peripheral nervous system. In situ, we observe high signal-to-noise ratios in the sciatic nerves of animals injected with fluorescently labeled Hsp1a and radiolabeled Hsp1a. Moreover, confocal microscopy on fresh nerve tissue shows the same high ratios of fluorescence, corroborating our in vivo results. This study indicates that fluorescently labeled and radiolabeled Hsp1a tracers could be used to identify and demarcate nerves in a clinical setting.

Trigeminal neuralgia as the sole neurological manifestation of COVID-19: A case report.

OBJECTIVE: To describe a case report of trigeminal neuralgia (TN) due to coronavirus disease-2019 (COVID-19). BACKGROUND: In March 2020, the World Health Organization declared COVID-19 as a pandemic. Respiratory system manifestations are dominant in this new disease. However, numerous case series and reviews have been published on the neurological manifestations, highlighting the potential neurotropism of the new coronavirus. METHODS: We describe a clinical case of TN during COVID-19 and we discuss the differential diagnosis and the potential pathogenic mechanism according to the literature. RESULTS: A 65-year-old man with general malaise and typical respiratory symptoms of COVID-19, who presented with paroxysmal lancinating pain in the right V1 trigeminal territory without other neurological symptoms. General blood test and neuroimaging study were normal. A rapid test showed positive IgG and IgM serologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was diagnosed with TN secondary to a viral infection by SARS-CoV-2. Facial pain resolved with the improvement of COVID-19. CONCLUSIONS: The new coronavirus SARS-CoV-2 is a possible etiology of secondary TN. Nevertheless, more studies are needed to elucidate the neuropathology of this viral infection.

Osseointegration of Sandblasted and Acid-Etched Implant Surfaces. A Histological and Histomorphometric Study in the Rabbit.

Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different types of sandblasted-etched surface implants, an SLA™ surface and a Nanoblast Plus™ surface. Roughness and chemical composition were evaluated by a white light interferometer microscope and X-ray photoelectron spectroscopy, respectively. The SLA™ surface exhibited the higher values (Ra 3.05 µm) of rugosity compared to the Nanoblast Plus™ surface (Ra 1.78 µm). Both types of implants were inserted in the femoral condyles of ten New Zealand white rabbits. After 12 weeks, histological and histomorphometric analysis was performed. All the implants were osseointegrated and no signs of infection were observed. Histomorphometric analysis revealed that the bone-implant contact % (BIC) ratio was similar around the SLA™ implants (63.74 ± 13.61) than around the Nanoblast Plus™ implants (62.83 ± 9.91). Both implant surfaces demonstrated a favorable bone response, confirming the relevance of the sandblasted-etched surface on implant osseointegration.

Selective Implantation of Diamines for Cooperative Catalysis in Isoreticular Heterometallic Titanium-Organic Frameworks.

We introduce the first example of isoreticular titanium-organic frameworks, MUV-10 and MUV-12, to show how the different affinity of hard Ti(IV) and soft Ca(II) metal sites can be used to direct selective grafting of amines. This enables the combination of Lewis acid titanium centers and available -NH2 sites in two sizeable pores for cooperative cycloaddition of CO2 to epoxides at room temperature and atmospheric pressure. The selective grafting of molecules to heterometallic clusters adds up to the pool of methodologies available for controlling the positioning and distribution of chemical functions in precise positions of the framework required for definitive control of pore chemistry.

Heterometallic Titanium-Organic Frameworks by Metal-Induced Dynamic Topological Transformations.

Reticular chemistry has boosted the design of thousands of metal and covalent organic frameworks for unlimited chemical compositions, structures, and sizable porosities. The ability to generate porous materials at will on the basis of geometrical design concepts is responsible for the rapid growth of the field and the increasing number of applications derived. Despite their promising features, the synthesis of targeted homo- and heterometallic titanium-organic frameworks amenable to these principles is relentlessly limited by the high reactivity of this metal in solution that impedes the controlled assembly of titanium molecular clusters. We describe an unprecedented methodology for the synthesis of heterometallic titanium frameworks by metal-exchange reactions of MOF crystals at temperatures below those conventionally used in solvothermal synthesis. The combination of hard (titanium) and soft (calcium) metals in the heterometallic nodes of MUV-10(Ca) enables controlled metal exchange in soft positions for the generation of heterometallic secondary building units (SBUs) with variable nuclearity, controlled by the metal incorporated. The structural information encoded in the newly formed SBUs drives an MOF-to-MOF conversion into bipartite nets compatible with the connectivity of the organic linker originally present in the crystal. Our simulations show that this transformation has a thermodynamic origin and is controlled by the terminations of the (111) surfaces of the crystal. The reaction of MUV-10(Ca) with first-row transition metals permits the production of crystals of MUV-101(Fe,Co,Ni,Zn) and MUV-102(Cu), heterometallic titanium MOFs isostructural with archetypical solids such as MIL-100 and HKUST. In comparison to de novo synthesis, this metal-induced topological transformation provides control over the formation of hierarchical micro-/mesopore structures at different reaction times and enables the formation of heterometallic titanium MOFs not accessible under solvothermal conditions at high temperature, thus opening the door for the isolation of additional titanium heterometallic phases not linked exclusively to trimesate linkers.