Acid-base Stimuli Research Articles

Piezo1 activity is regulated independently in principal and intercalated cells of the renal collecting duct

Water-electrolyte transport in the distal segments of the renal tubule, including the collecting duct (CD), is regulated by mechanical forces arising from changes in fluid flow and osmolarity. Such mechanical stress is known to directly activate Ca2+-permeable Piezo1 channel triggering various downstream effectors under different physiological conditions. However, the functional significance of Piezo1 in morphologically and physiologically distinct principal (PC) and intercalated (IC) cells of the CD is yet to be determined. Here, we implemented electrophysiological and imaging tools to investigate pharmacological Piezo1 activation in PC and IC of freshly isolated intact and split-opened CDs. For this purpose, we applied a variety of systemic treatments, including water restrictions, diuretic injections and dietary manipulations. We observed significantly greater intracellular Ca2+ ([Ca2+]i) signal in PC (AQP2-positive cells) than in IC (AQP2-negative) in freshly isolated split-opened CDs upon application of Piezo1 selective agonists, Yoda-1 and Jedi-2. Patch-clamp analysis in cell-attached configuration allowed us recording of a Yoda-1-activated non-selective channel with 18.6±0.7 pS conductance on both apical and basolateral membranes. These results are in a good agreement with immunofluorescent detection of Piezo1 at both apical and basolateral sides in renal sections and isolated split-opened collecting ducts. Acute stimulation of flow with furosemide injections (2 mg/kgBW, 18h and 2h prior to experimentation) stimulated the elevation of Yoda-1-induced Piezo1-dependent [Ca2+]i elevation in PCs, but not in ICs of split-opened collecting ducts. However, prolonged increased flow in the collecting duct by high K+ diet (for 1 week) decreased Yoda-1-dependent Ca2+ influx in the absence of apparent changes in Piezo1 levels pointing to its inactivation. This led to notable flattening of CD cells, suggesting cytoskeleton reorganization due to increased perfusion pressure existing during high K+ intake. At the same time, anti-diuresis with water restrictions led to reduced Piezo1-dependent [Ca2+]i elevation in PCs of split-opened CDs. Consistently, induction of metabolic acidosis with NH4Cl−supplemented water Piezo1 activity in IC, but not in PC. In summary, our results directly demonstrate functional Piezo1 expression in collecting duct PCs (more) and ICs (less) on both apical and basolateral sides. We also show that acute changes in fluid flow regulate Piezo1 function in PCs, whereas channel activity in ICs responds to systemic acid-base stimuli. This research was supported by NIH-NIDDK DK117865, DK119170, AHA EIA35260097 (to O. Pochynyuk) and AHA-23POST1020372 (to K. Pyrshev). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Independent regulation of Piezo1 activity by principal and intercalated cells of the collecting duct

The renal collecting duct is continuously exposed to a wide spectrum of fluid flow rates and osmotic gradients. Expression of a mechanoactivated Piezo1 channel is the most prominent in the collecting duct. However, the status and regulation of Piezo1 in functionally distinct principal and intercalated cells (PCs and ICs) of the collecting duct remain to be determined. We used pharmacological Piezo1 activation to quantify Piezo1-mediated [Ca2+]i influx and single-channel activity separately in PCs and ICs of freshly isolated collecting ducts with fluorescence imaging and electrophysiological tools. We also employed a variety of systemic treatments to examine their consequences on Piezo1 function in PCs and ICs. Piezo1 selective agonists, Yoda-1 or Jedi-2, induced a significantly greater Ca2+ influx in PCs than in ICs. Using patch clamp analysis, we recorded a Yoda-1-activated nonselective channel with 18.6± 0.7 pS conductance on both apical and basolateral membranes. Piezo1 activity in PCs but not ICs was stimulated by short-term diuresis (injections of furosemide) and reduced by antidiuresis (water restriction for 24 h). However, prolonged stimulation of flow by high K+ diet decreased Yoda-1-dependent Ca2+ influx without changes in Piezo1 levels. Water supplementation with NH4Cl to induce metabolic acidosis stimulated Piezo1 activity in ICs but not in PCs. Overall, our results demonstrate functional Piezo1 expression in collecting duct PCs (more) and ICs (less) on both apical and basolateral sides. We also show that acute changes in fluid flow regulate Piezo1-mediated [Ca2+]i influx in PCs, whereas channel activity in ICs responds to systemic acid-base stimuli.

Engineering Isomeric AIEgens Containing Tetraphenylpyrazine for Dual Memory Storage.

Tetraphenylpyrazine (TPP) is a promising heterocycle-based aggregation-induced emission luminogen (AIEgen) which has sparked multiple applications in organic light-emitting diodes, sensors, and biotherapy. However, the utility of it in developing information storage materials is relatively rare. Moreover, TPP is mostly employed as an electronic acceptor in molecular design, while the consideration of it as an electronic donor is attractive in studies which may provide a full understanding of its property to tailor the materials. In this work, we synthesize three TPP-based molecules by decorating it with acrylonitrile and isomeric pyridine units, which show AIE behavior by property inheritance from their parent unit. Interestingly, the effective intramolecular charge transfer takes place from the TPP electronic donor to the acrylonitrile and pyridine electronic acceptor, therefore inducing a remarkable solvatochromic effect as the solvent polarity improves. Moreover, it is revealed that the isomeric effect of the nitrogen atom in the pyridines may pose an influence on the absorption, solvatochromism, and AIE behavior. In addition, the acrylonitrile and pyridine groups are reactive to light and acid-base stimuli with irreversible and reversible responses, respectively. Combined with the high light-harvesting ability of these AIEgens, they show great potential in the stimuli-responsive materials for dual information storage.

Construction of Mechanically Interlocked Fluorescence Photoswitchable [2]Rotaxane with Aggregation-Induced Emission and Molecular Shuttling Behaviors

Here, we report the design, synthesis, and optical behaviors of a multistimuli responsive [2]rotaxane system constructed from noncovalent interactions between diarylethene (DAE)-based axle and a tetraphenylethene (TPE)-based macrocycle using a snapping supramolecular assembly approach. The shuttling behavior of the macrocycle (Ring-TPE) between dialkylammonium and urea stations could be realized by the influence of acid-base stimuli using 1H NMR spectroscopy. Switching between the open-form (OF) [2]rotaxanes (DAE-R1-OF and DAE-R2-OF) is highly reversible using external chemical stimuli. These rotaxane systems exhibit enhanced blue fluorescence in their aggregation states despite being weak or nonemissive in solution. A significant increase in fluorescence emission intensity of typical TPE in DAE-R1-OF and DAE-R2-OF at ca. 467 nm was observed as the water content was increased to ≥70% in CH3CN/H2O solvent mixtures. However, the fluorescence emission of TPE at its maximum aggregation state (95% fw) could be rapidly quenched upon UV light irradiation due to a very efficient energy transfer from the excited TPE (donor) to the closed form of DAE (acceptor). In contrast, OF DAE does not affect the fluorescence of the TPE unit, which remains at high level. Furthermore, the [2]rotaxanes showed excellent photochromic and fluorescent properties in solution, making them suitable for information storage and reversible photo-patterning applications.

High-contrast fluorescence modulation driven by intramolecular photocyclization and protonation of bithienylpyridine functionalized α-cyanostilbene

We report herein a light-inducible fluorescence conversion and an acidochromism based on the bithienylpyridine functionalized α-cyanostilbene luminogen (E-CTP). The thienylcyanostyrene unit in this luminogen endows E-CTP AIEE property and 365 nm light-induced fluorescence conversion with high contrast in color (Δλem = 85 nm) and strong intensity. The fluorescence conversion of this molecular system might be driven by an intramolecular photocyclization rather than the commonly occurred intermolecular photodimerization for the α-cyanostilbene system as indicated by UV, PL, TCL-MS as well as NMR spectra measurements. Due to the bithienyl-pyridine in its skeleton, the optoelectronic properties of this luminogen can also be tuned by protonation. The luminogen shows 6 fold fluorescence enhancement and 110 nm emission red-shift in solution upon addition of trifluoroacetic acid (TFA). The optical feature of the reversible recoverability for E-CTP under acid-base stimuli in film was utilized to prepare security paper. Moreover, cooperating the acidochromism with the photo-induced fluorescence conversion of E-CTP, multicolor light-painting pattern was achieved.

Controlling molecular shuttling in a rotaxane with weak ring recognition sites.

We describe a rotaxane molecular shuttle encompassing triazolium and tertiary ammonium units as weak recognition sites for the ring. Such a design, which differs from that of typical controllable rotaxanes, allows the precise tuning of the ring distribution among the two sites - i.e., the coconformational equilibrium - by changing the solvent polarity or the nature of the counteranions. Shuttling of the ring between the two stations can also be toggled by acid-base stimuli. Such an approach is paradigmatic to obtain rotaxanes that can sense environmental changes and transduce them into a coconformational response and opens avenues for novel applications in sensing and stimuli-responsive materials.

Acceptorless Dehydrogenation of Alcohols and Transfer Hydrogenation of Aldehydes in Water Using a Single Bifunctional, Bistate, Water-soluble Ruthenium Catalyst.

A water-soluble bifunctional, bistate ruthenium catalyst has been developed using the 8-aminoquinoline ligand which responds to an acid-base stimuli and is catalytically active for two complementary reactions. The "Ru-amino state" is highly active for catalytic transfer hydrogenation of various aldehydes using formic acid as the hydrogen source resulting in a range of primary alcohols. On the other hand, the "Ru-amido state" is active for the acceptorless dehydrogenation of alcohols to yield carboxylate salts or ketones. The reactions can be carried out in air without an inert atmosphere and the products can be purified by simple extraction without the use of any chromatographic techniques. A range of functional groups which include electron-rich and deficient (hetero)arenes and alkenes, alkynes, halides, esters, cyano, and nitro groups, are all well tolerated, indicating excellent chemoselectivity for transfer hydrogenation.

A Schiff base with excited-state intramolecular proton transfer and its Zinc(II) complex: Mechanochromic luminescence and acid-base stimuli response

A new Schiff base compound (HL·CH3COOH) with D-A structure and its zinc(II) complex (1) were successfully obtained. Due to the introduction of diethylamino and rotatable aromatic rings, both HL·CH3COOH and the complex adopt loosely packing patterns. HL·CH3COOH exhibits keto-form emission due to the excited-state intramolecular proton transfer (ESIPT) process, while complex 1 shows enol-form emission. They all show reversible mechanochromic luminescence (MCL) behavior, which is caused by the phase transformation from crystalline state to amorphous state revealed by Powder X-ray diffraction (PXRD) studies, and is accompanied by the departure of CH3COOH molecules for HL·CH3COOH. HL·CH3COOH and complex 1 can be protonated under the fumigation of HCl, resulting in the acidochromic properties, accompanied with the phase transformation. HCl also destroyed the interactions between CH3COOH and Schiff base molecules, leading to the departure of acetic acid molecules. More interestingly, HL·CH3COOH also exhibited NH3-stimuli response properties due to the prohibition of the ESIPT process.

An acid-base responsive linear-cyclic polymer rotaxane molecular shuttle with fluorescence signal output

The preparation of intelligent-responsive materials with controllable topology structure has long been a significant objective for chemists in the field of materials science. In this paper, we designed and prepared a linear-cyclic reversible topological structure polymer based on the bistable [1]rotaxane molecular shuttle. A ferrocene-functionalized [1]rotaxane and naphthalimide fluorophore group are introduced into the both ends of the polymer, which exhibit distance-induced photo-electron transfer effect. The structural transformation between linear and cyclic state of polymer is demonstrated by simple acid-base stimuli, accompanying visual fluorescence changes. The transformation process was characterized by 1H NMR spectra and fluorescence spectra. This work provides a novel strategy to construct functionalized polymers with topological structure.

Stimuli-Responsive Two-Dimensional Supramolecular Polymers Based on Trinuclear Platinum(II) Scaffolds: Reversible Modulation of Photoluminescence, Cavity Size, and Water Permeability.

Here we report the first two-dimensional (2D) supramolecular polymer, which has varying structure and function arising from the perturbation of noncovalent metal···metal interactions in response to acid-base stimuli. This 2D assembly possesses a positively charged, honeycomb-like nanostructure consisting of trinuclear alkynylplatinum(II) terpyridine complexes appended with acid-sensitive dimethylamino groups. Upon addition of acids and bases, reversible switching mediated by protonation and deprotonation of dimethylamino and dimethylammonium moieties intrinsically alters the positive charge density of the constituent cationic units, which causes interior cavities to adaptively adjust their size, accompanied by drastic photoluminescence changes. When water molecules pass through the membranes obtained from 2D supramolecular polymers, the permeating flux can also be tuned by the pH values of the buffer media. This work paves the way toward supramolecularly engineered 2D smart materials with stimuli-responsive properties.

Reversible stimulus-responsive coordination polymers mainly involving conversion between the lone-pair–π and cation–π interactions

A new 3-position substituted imidazo[1,2-a]pyridine ligand, 4-(2-chloroimidazo[1,2-a] pyridine-3-carboxamido)phthalic acid (H2L), was conveniently synthesized and acts as a three-connecting T-shaped building block. Based on this ligand, two isostructural coordination polymers, [ML(H2O)] n (M = Zn (1) and Co (2)) with a rare one-dimensional (1D) ladder-like chain structure, were solvothermally synthesized and structurally characterized. There exist hydrogen bond and lone-pair–π interactions between two adjacent ladder chains. Compared to the H2L ligand, coordination polymer 1 reveals a blue-shifted emission stemming from ligand-to-metal charge transfer, meanwhile, coordination polymer 2 presents a dominant antiferromagnetism. Interestingly, the carboxylate anion (COO−) in coordination polymers 1 and 2 could be protonated into carboxylic acid (–COOH), upon exposure to HCl vapor. As a result, coordination polymers 1 and 2 display reversible luminescent switching in the response to acid-base vapor stimuli, which mainly originates from the conversion between lone-pair–π and cation–π interactions mediated by the protonation-deprotonation processes. Such stimulus-responsive conversion between lone-pair–π and cation–π interactions is first reported in coordination polymers, and provides a promising approach to design and construct smart coordination polymer materials.

Switch in Catalyst State: Single Bifunctional Bi-state Catalyst for Two Different Reactions.

Disclosed here is a molecular switch which responds to acid-base stimuli and serves as a bi-state catalyst for two different reactions. The two states of the switch serve as a highly active and poorly active catalyst for two catalytic reactions (namely a hydrogenation and a dehydrogenative coupling) but in a complementary manner. The system was used in an assisted tandem catalysis set-up involving dehydrogenative coupling of an amine and then hydrogenation of the resulting imine product by switching between the respective states of the catalyst.

Sailboat‐Shaped Self‐Complexes that Function as Controllable Rotary Switches

Bis(p‐phenylene)‐34‐crown‐10‐based substituted macrocycles bearing a dibenzylammonium side arm form sailboat‐shaped self‐complexes, in which the arm of the substituted macrocycle sticks into the cavity of the crown ether instead of threading into it. On the basis of this simple system, we easily constructed controllable rotary switches. The decomplexation/recomplexation process was realized by acid–base stimuli, and the switching process was successfully used to control the dethreading/rethreading of paraquat as a guest through the cavity of the BPP34C10 moiety of the substituted macrocycles, which rendered them promising candidates for fabricating more novel interlocked structures and molecular devices.

Acid-Base-Triggered Structural Transformation of a Polyoxometalate Core Inside a Dodecahedrane-like Silver Thiolate Shell.

Self-assembly of metavanadate and organosilver(I) salts leads to a novel dodecahedrane-like [Ag30 ((t) BuS)20 ](10+) silver(I) thiolate nanocage that tightly wraps an unusual C2h polyoxovanadate anion. The polyoxovanadate core undergoes transformation to a D3d configuration upon acidification, and reverts back to its original C2h structure upon addition of base. Chromism was observed for the silver(I) thiolate cluster during the configurational change of the central polyoxovanadate core; the color of the solution changes reversibly from green to dark yellow. This work represents the first reported example of chromic polyoxometalate-templated silver(I) thiolate shells that respond to external acid-base stimuli. It also represents an important advance in providing crystallographic proof that structural transformations occur in a nanoscale core-shell cluster.

Aggregation-induced emission behavior of a pH-controlled molecular shuttle based on a tetraphenylethene moiety.

Tetraphenylethene (TPE) with aggregation-induced emission (AIE) behavior as a popular backbone is applied widely in the construction of functional supramolecular systems. In this work, a TPE-based linear molecule having amide and amine units is synthesized. Its ammonium template is used to construct the N-hetero crown ether-based [2]rotaxane by the template-directed clipping approach. Their structures are well-characterized by NMR, MALDI-TOF-MS and elemental analysis. Owing to the existence of the amide unit, [2]rotaxane possesses the function of a molecular shuttle. The shuttling motion of the macrocycle component between the ammonium station and the amide station can be driven by external acid-base stimuli in solution, accompanied by changes in visual behavior. Investigation on their AIE behavior shows that (1) ammonium reaches the aggregation state almost in the presence of same water with the deprotonated form of ammonium; (2) the [2]rotaxane that the macrocycle component locates at the site of ammonium forms the aggregation state in the presence of less water than the deprotonated [2]rotaxane that the macrocycle component locates at the site of the amide, attributed to stronger interaction between the crown ether component and the TPE unit of the template component when the distance between the two is shorter. The result indicates that the shuttling motion of the macrocycle component can adjust the aggregation state of AIE molecules.

A switchable bis-branched [1]rotaxane featuring dual-mode molecular motions and tunable molecular aggregation.

A multifunctional bis-branched [1]rotaxane containing a perylene bisimide (PBI) core and two identical bistable[1]rotaxane arms terminated with ferrocene units was prepared and characterized by (1)H NMR, (13)C NMR, and 2D ROESY NMR spectroscopies and by HR-ESI spectrometry. The system is shown to possess several key features: (1) In acetone solution, external acid-base stimuli can result in relative mechanical movements of its ring and thread, which can induce extension and contraction movements of the whole system accompanied by a rotational movement of the ferrocene units, thus realizing dual-mode molecular motions, and the optimized conformations at different states are obtained through molecular dynamics simulations employing the general Amber force field. (2) The introduction of PBI enables the system fluorescence encoding through distance-dependent photoinduced electron transfer process from the ferrocene units to the PBI fluorophore. (3) The addition of Zn(2+) can increase the degree of aggregation of the system, while adding base hinders aggregation because of the movement of the macrocycle. The tunable aggregated nanostructural morphologies of [1]rotaxane were examined by scanning electron microscopy. These results can pave the way to achieve precise control of integrated and coupling nanomechanical motions at a single-molecule level and provide more insight into controlling the aggregate behavior of switchable mechanically interlocked molecules.

An acid/base switchable and reversibly cross-linkable polyrotaxane

A main chain-type polyrotaxane was fabricated based on the DP24C8/dialkylammonium recognition motif, in which the host could be controllably shuttled on the axle of the polyrotaxane upon acid–base stimuli and reversibly cross-linked via Pd coordination and decoordination.

A Novel Star-Shaped Zinc Porphyrin Cored [5]Rotaxane

A novel star-shaped zinc porphyrin cored [5]rotaxane with four rotaxane arms was synthesized and well characterized by (1)H, (13)C NMR spectroscopy and HR-ESI mass spectrometry. The introduction of the zinc porphyrin core enabled the [5]rotaxane to have a fixed shape and symmetrical structure, and the simultaneous shuttling motion of four macrocycles can be driven by external acid-base stimuli. This kind of topological structure exhibits important potential in the design and construction of large sophisticated assemblies.

A Ferrocene-Functionalized [2]Rotaxane with Two Fluorophores as Stoppers

In the past few decades, bistable [2]rotaxanes have been extensively studied because of their applications in the fields of functional molecules and molecular machines. In this paper, a di-ferrocene-functionalized [2]rotaxane with two fluorophores as stoppers was designed, prepared, and studied. In this bistable [2]rotaxane, a dibenzo-24-crown-8 macrocycle functionalized with two ferrocene moieties as electron donors can reversibly shuttle between two distinct stations, namely, a dialkylammonium recognition site and a N-methyltriazolium recognition site, by external acid-base stimuli, which has been demonstrated using (1)H NMR spectroscopy. It has been shown that, by introducing two ferrocene units into the macrocycle component, the fluorescence of two fluorescent stoppers, namely, the anthracene fluorophore and the 4-morpholin-naphthalimide fluorophore, can be changed in an alternate mode by an adjustable, distance-dependent photoinduced electron transfer process that occurs between the ferrocene electron donors and each of the two fluorophores.

Dual-Mode Control of PET Process in a Ferrocene-Functionalized [2]Rotaxane with High-Contrast Fluorescence Output

The shuttling motion of the ferrocene-functionalized macrocycle between the dibenzylammonium and the N-methyltriazolium recognition sites in a bistable [2]rotaxane, as well as the photoinduced electron transfer process occurring between ferrocene units and the morpholin-naphthalimide fluorescent stopper, can be adjusted not only by acid-base stimuli but also addition-removal of the fluoride anion, along with remarkable, high-contrast fluorescent intensity changes.