DNA-Modulated and Mechanoresponsive Excitonic Couplings Reveal Chiroptical Correlation of Conformation, Tension, and Dynamics of DNA Self-Assembly.

Study of the conformational and mechanical behaviors of biomolecular assemblies is vital to the rational design and realization of artificial molecular architectures with biologically relevant functionality. Here, we revealed DNA-modulated and mechanoresponsive excitonic couplings between organic chromophores and verified strong correlations between the excitonic chiroptical responses and the conformational and mechanical states of DNA self-assemblies irrespective of fluorescence background interference. Besides, the excitonic chiroptical effect allowed sensitive monitoring of DNA self-assembled nanostructures due to small molecule bindings or DNA strand displacement reactions. Moreover, we developed a new chiroptical reporter, a DNA-templated dimer of an achiral cyanine5 and an intrinsically chiral BODIPY, that exhibited unique multiple-split spectral line shape of exciton-coupled circular dichroism, largely separated response wavelengths, and enhanced anisotropy dissymmetry factor (g-factor). These results shed light on a promising chiroptical spectroscopic tool for studying biomolecular recognition and binding, conformation dynamics, and soft mechanics in general.

¿Es precisa la ecografía para el diagnóstico de pólipos vesiculares? Revisión de las piezas de colecistectomía de pacientes diagnosticados de pólipo vesicular durante un periodo de 14 años / Is ultrasonography accurate for the diagnosis of gallbladder polyps? A review of cholecystectomy specimens from patients diagnosed with gallbladder polyps over a 14 years period

Introducción: La incidencia de pólipos vesiculares es del 0,3-12%. Es importante diferenciar los seudopólipos (pólipos de colesterol, adenomiomatosis o pólipos inflamatorios) de los pólipos verdaderos (adenomas y adenocarcinomas). Los principales factores de riesgo de malignización son el tamaño superior a 6-10mm, crecimiento rápido del mismo, morfología sésil, etnia india y colangitis esclerosante primaria. La ecografía es el gold standard para su diagnóstico. Sin embargo, la mayoría de los pólipos diagnosticados por ecografía son seudopólipos. El objetivo del estudio es analizar si la ecografía es precisa para diagnosticar los pólipos verdaderos en los pacientes cuya indicación quirúrgica ha sido este diagnóstico ecográfico. Métodos: Estudio observacional retrospectivo de los pacientes intervenidos en nuestro centro, desde el año 2007 al 2019, de colecistectomía electiva por presentar pólipos vesiculares. La cirugía se indicó en pacientes sintomáticos y/o con factores de riesgo. El estudio fue aprobado por el Comité Ético de Investigación Clínica de nuestro hospital. Resultados: Se han incluido 124 pacientes. En todos ellos se ha realizado colecistectomía laparoscópica. La edad media fue de 55,4 años y el 61% eran mujeres. El 65% tenían síntomas biliares. En nuestro estudio, solo 3 pacientes presentaron pólipos verdaderos (2,4%). Todos ellos, fueron adenomas tubulares. El resto de los pacientes resultaron falsos positivos (97,6%). El tamaño de los adenomas fue de 11, 6 y 5mm. La cirugía se indicó por tamaño o por clínica asociada. Conclusiones: La ecografía no es precisa para el diagnóstico de pólipos vesiculares verdaderos. La validación de otras pruebas complementarias para el diagnóstico de pólipos en pacientes asintomáticos podría ser relevante para evitar cirugías innecesarias. (AU)

Introduction: The incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the potential to become malignant, and true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are size>6-10mm, rapid growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. However, most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyze whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. Methods: We conducted a retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study was approved by the Clinical Research Ethics Committee of our hospital. Results: Our study included 124 patients who had undergone elective laparoscopic cholecystectomy. Mean age was 55.4 years, and 61% were women. In total, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2.4%), all of which were tubular adenomas. The remainig patients were false positives (97.6%). The adenoma sizes were 11, 6 and 5mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. Conclusion: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. The validation of other complementary tests for the diagnose gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries. (AU)

Is ultrasonography accurate for the diagnosis of gallbladder polyps? A review of cholecystectomy specimens from patients diagnosed with gallbladder polyps over a 14-years period.

INTRODUCTION: Incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the capacity to become malignant, from true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are >6-10 mm, growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. Most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyse whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. METHODS: Retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study has been approved by the Clinical Research Ethics Committee of our hospital. RESULTS: We included 124 patients in our study. An elective laparoscopic cholecystectomy was performed in all of them. The mean age was 55,4 years and 61% were women. Of all patients, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2,4%). All of them were tubular adenomas. The rest of patients were false positives (97,6%). The adenoma size was 11, 6 and 5 mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. CONCLUSION: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. Validation of other complementary tests for the diagnosis of gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries.

Polar ammoniostyryls easily converting a clickable lipophilic BODIPY in an advanced plasma membrane probe.

A very simple, small and symmetric, but highly bright, photostable and functionalizable molecular probe for plasma membrane (PM) has been developed from an accessible, lipophilic and clickable organic dye based on BODIPY. To this aim, two lateral polar ammoniostyryl groups were easily linked to increase the amphiphilicity of the probe and thus its lipid membrane partitioning. Compared to the BODIPY precursor, the transversal diffusion across lipid bilayers of the ammoniostyryled BODIPY probe was highly reduced, as evidenced by fluorescence confocal microscopy on model membranes built up as giant unilamellar vesicles (GUVs). Moreover, the ammoniostyryl groups endow the new BODIPY probe with the ability to optically work (excitation and emission) in the bioimaging-useful red region, as shown by staining of the plasma membrane of living mouse embryonic fibroblasts (MEFs). Upon incubation, this fluorescent probe rapidly entered the cell through the endosomal pathway. By blocking the endocytic trafficking at 4 °C, the probe was confined within the PM of MEFs. Our experiments show the developed ammoniostyrylated BODIPY as a suitable PM fluorescent probe, and confirm the synthetic approach for advancing PM probes, imaging and science.

Triplet-triplet sensitizing within pyrene-based COO-BODIPY: a breaking molecular platform for annihilating photon upconversion.

We envisioned a new approach for achieving triplet-triplet annihilation-assisted photon upconversion based on the rational design of a heavy-atom-free, all-organic and photoactivatable triplet-triplet synergistic multichromophoric molecular assembly. This single molecular architecture is easily built by covalently anchoring triplet-annihilator units (pyrenes) to a triplet-photosensitizer moiety (BODIPY), to improve the effectiveness and probability of the required triplet-triplet energy transfer and the ulterior triplet-triplet annihilation. This unprecedented design takes advantage of the high synthetic accessibility and chemical versatility of the COO-BODIPY scaffold. The laser-induced photophysical characterization, assisted by computational simulations (quantum mechanics calculations at single molecular level and molecular dynamics in a solvent cage), identifies the key factors to finely control the intersystem crossing and reverse intersystem crossing probability, pivotal to improve energy transfer efficiency between the involved triplet states. Likewise, theoretical simulations highlight the relevance of the new photoactivable chromophoric design to promote intra- and inter-molecular triplet-triplet annihilation towards enhanced photon upconversion, yielding noticeable fluorescence from pyrene units even under unfavorable conditions (aerated solutions of low concentration at room temperature). The understanding of the complex dynamics sustained by this single molecular architecture could approach the next generation of chemically accessible and low-cost materials enabling fluorescence by photon upconversion mediated by triplet-triplet annihilation.

BINOL blocks as accessible triplet state modulators in BODIPY dyes.

BINOL moieties of different electronic demand are useful blocks for enabling the photo-production and modulation of triplet excited states in readily-accesible BINOL-based O-BODIPY dyes from standard F-BODIPY precursors. The rapid and rational development of smarter triplet-enabling BODIPY dyes on the basis of this strategy (e.g., TADF biomarker 4a or room temperature phosphor 4g) paves the way for advancing photonic applications based on organic triplet photosensitizers.

Insight into the Influence of the Chiral Molecular Symmetry on the Chiroptics of Fluorescent BINOL-Based Boron Chelates.

The prominent influence of the molecular symmetry, as defined by the symmetry point group, on the chiroptical behavior (electronic circular dichroism and, especially, circularly polarized luminescence) of simple fluorescent boron chelates (BODIPY and related BOPHY analogues) is studied and discussed. It is shown that increasing the dye symmetry by means of the D3 chiral symmetry group is a workable design option to enhance the level of differential emission of right- and left-circularly polarized light in BODIPY dyes and related emitters, and that the influence of the level of symmetry is stronger than the influence of the higher number of chiral moieties perturbing the acting achiral chromophore.

BINOLated aminostyryl BODIPYs: a workable organic molecular platform for NIR circularly polarized luminescence.

The accessible at-boron-BINOLated 3,5-bis(4-aminostyryl)ated BODIPY scaffold is highlighted as a workable platform for developing enantiopure small organic molecules exhibiting CPL in the NIR region, even in water solution, the latter being key for CPL-based bioapplications. Synthetic simplicity, noticeable chiroptical efficiency in the NIR and the possibility to access water-soluble emitters pave the way for advancing CPL tools based on organic emitters and NIR radiation.

Multichromophoric COO-BODIPYs: an advantageous design for the development of energy transfer and electron transfer systems.

COO-BODIPYs are highlighted as cutting edge scaffolds for easy access to a new generation of multichromophoric architectures with enhanced (photo)chemical stability, showing either boosted capability for excitation energy transfer, glow fluorescence and laser emission, or photoinduced electron transfer. The new finding paves the way for the rapid development of smarter organic dyes for advancing photonics and optoelectronics.

BCl3-Activated Synthesis of COO-BODIPY Laser Dyes: General Scope and High Yields under Mild Conditions.

A general and straightforward method for the synthesis of COO-BODIPYs from F-BODIPYs and carboxylic acids is established. The method is based on the use of boron trichloride to activate the involved substitution of fluorine, which leads to high yields through rapid reactions under soft conditions. This mild method opens the way to unprecedented laser dyes with outstanding efficiencies and photostabilities, which are difficult to obtain by the current methods.

Manipulating Charge-Transfer States in BODIPYs: A Model Strategy to Rapidly Develop Photodynamic Theragnostic Agents.

On the basis of a family of BINOL (1,1'-bi-2-naphthol)-based O-BODIPY (dioxyboron dipyrromethene) dyes, it is demonstrated that chemical manipulation of the chromophoric push-pull character, by playing with the electron-donating capability of the BINOL moiety (BINOL versus 3,3'-dibromoBINOL) and with the electron-acceptor ability of the BODIPY core (alkyl substitution degree), is a workable strategy to finely balance fluorescence (singlet-state emitting action) versus the capability to photogenerate cytotoxic reactive oxygen species (triplet-state photosensitizing action). It is also shown that the promotion of a suitable charge-transfer character in the involved chromophore upon excitation enhances the probability of an intersystem crossing phenomenon, which is required to populate the triple state enabling singlet oxygen production. The reported strategy opens up new perspectives for rapid development of smarter agents for photodynamic theragnosis, including heavy-atom-free agents, from a selected organic fluorophore precursor.

Chiral Microneedles from an Achiral Bis(boron dipyrromethene): Spontaneous Mirror Symmetry Breaking Leading to a Promising Photoluminescent Organic Material.

Supramolecular self-assembly of a highly flexible and achiral meso bis(boron dipyrromethene) [bis(BODIPY)] dye straightforwardly yields fluorescent microfibers, exhibiting an intriguing anisotropic photonic behavior. This performance includes the generation of chiroptical activity owing to spontaneous mirror symmetry breaking (SMSB). Repetition of several self-assembly experiments demonstrates that the involved SMSB is not stochastic but quasi deterministic in the direction of the induced chiral asymmetry. The origin of these intriguing (chiro)photonic properties is revealed by fluorescent microspectroscopy studies of individual micrometric objects, combined with X-ray diffraction elucidation of microcrystals. Such a study demonstrates that J-like excitonic coupling between bis(BODIPY) units plays a fundamental role in their supramolecular organization, leading to axial chirality. Interestingly, the photonic behavior of the obtained fibers is ruled by inherent nonradiative pathways from the involved push-pull chromophores, and mainly by the complex excitonic interactions induced by their anisotropic supramolecular organization.

Modulating ICT emission: a new strategy to manipulate the CPL sign in chiral emitters.

A new strategy to manipulate the circularly polarized luminescence (CPL) handedness in chiral emitters, based on modulating the population of an emissive ICT state, is proposed. Such a strategy is particularly interesting for conformationally rigid and non-aggregating chiral organic emitters, opening up new perspectives for the development of CPL applications based on organic molecules.

C*-BODIPYs: Exploring a New Strategy to Transfer Chirality towards BODIPY Chiroptics†.

C*-BODIPYs, that is, boron dipyrromethenes (BODIPYs) which have chiral carbons attached directly to the boron center, are introduced for the first time. These novel chiral BODIPYs mean a new strategy for the chiral perturbation of the inherently achiral BODIPY chromophore that is directed to enable chiroptical properties. Their preparation is very simple and only implies the complexation of a dipyrrin with an enantiopure dialkylborane having boron bonded to chiral carbons.

Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking.

The T1 parvovirus Minute Virus of Mice (MVM) was used to study the roles that phosphorylation and N-terminal domains (Nt) configuration of capsid subunits may play in icosahedral nuclear viruses assembly. In synchronous MVM infection, capsid subunits newly assembled as two types of cytoplasmic trimeric intermediates (3VP2, and 1VP1:2VP2) harbored a VP1 phosphorylation level fivefold higher than that of VP2, and hidden Nt. Upon nuclear translocation at S phase, VP1-Nt became exposed in the heterotrimer and subsequent subviral assembly intermediates. Empty capsid subunits showed a phosphorylation level restored to VP1:VP2 stoichiometry, and the Nt concealed in their interior. However ssDNA-filled virus maturing at S/G2 lacked VP1 phosphorylation and one major VP2 phosphopeptide, and exposed VP2-Nt. Endosomal VP2-Nt cleavage resulted in VP3 subunits devoid of any phospholabel, implying that incoming viral particles specifically harbor a low phosphorylation status. Phosphorylation provides a mechanistic coupling of parvovirus nuclear assembly to the cell cycle.

Chiral Organic Dyes Endowed with Circularly Polarized Laser Emission.

The direct generation of efficient, tunable, and switchable circularly polarized laser emission (CPLE) would have far-reaching implications in photonics and material sciences. In this paper, we describe the first chiral simple organic molecules (SOMs) capable of simultaneously sustaining significant chemical robustness, high fluorescence quantum yields, and circularly polarized luminescence (CPL) ellipticity levels (|glum|) comparable to those of similar CPL-SOMs. All these parameters altogether enable efficient laser emission and CPLE with ellipticity levels 2 orders of magnitude stronger than the intrinsic CPL ones.

Modulation of ICT probability in bi(polyarene)-based O-BODIPYs: towards the development of low-cost bright arene-BODIPY dyads.

We report the synthesis, and spectroscopic and electrochemical properties of a selected library of novel spiranic O-BODIPYs bearing a phenol-based bi(polyarene) unit tethered to the boron center through oxygen atoms. These dyes constitute an interesting family of arene-BODIPY dyads useful for the development of photonic applications due to their synthetic accessibility and tunable photonic properties. It is demonstrated that the electron-donor capability of the involved arene moiety switches on a non-emissive intramolecular charge transfer (ICT) state, which restricts the fluorescence efficiency of the dyad. Interestingly, the influence of this non-radiative deactivation channel can be efficiently modulated by the substitution pattern, either at the dipyrrin ligand or at the polyarene moiety. Thus, dyads featuring electron-rich dipyrrin and electron-poor polyarene show lower or almost negligible ICT probability, and hence display bright fluorescence upon dual excitation at far-away spectral regions. This synthetic approach has allowed the easy development of low-cost efficient ultraviolet-absorbing visible-emitting cassettes by selecting properly the substitution pattern of the involved key units, dipyrrin and bi(polyarene), to modulate not only absorption and emission wavelengths, but also fluorescence efficiencies.

N-BODIPYs Come into Play: Smart Dyes for Photonic Materials.

N-BODIPYs (diaminoboron dipyrromethenes) are unveiled as a new family of BODIPY dyes with huge technological potential. Synthetic access to these systems has been gained through a judicious design focused on stabilizing the involved diaminoboron chelate. Once stabilized, the obtained N-BODIPYs retain the effective photophysical behavior exhibited by other boron-substituted BODIPYs, such as O-BODIPYs. However, key bonding features of nitrogen compared to those of oxygen (enhanced bond valence and different bond directionality) open up new possibilities for functionalizing BODIPYs, allowing an increase in the number of pendant moieties (from two in O-BODIPYs, up to four in N-BODIPYs) near the chromophore and, therefore, greater control of the photophysics. As a proof of concept, the following findings are discussed: (1) the low-cost and straightforward synthesis of a selected series of N-BODIPYs; (2) their outstanding photophysical properties compared to those of related effective dyes (excellent emission signatures, including fluorescence in the solid state; notable lasing capacities in the liquid phase and when doped into polymers; improved laser performance compared to the parent F-BODIPYs); (3) the versatility of the diaminoboron moiety in allowing the generation of multifunctionalized BODIPYs, permitting access to both symmetric and asymmetric dyes; (4) the capability of such versatility to finely modulate the dye photophysics towards different photonic applications, from lasing to chemosensing.

Push-pull flexibly-bridged bis(haloBODIPYs): solvent and spacer switchable red emission.

A series of uncommon bis(BODIPYs), involving a flexible bridge linking the BODIPY α-positions and key functionalities to efficiently give an electronic push-pull effect, has been synthesized, as well as photophysically and structurally studied. It is demonstrated that the designed push-pull effect efficiently enables intramolecular charge transfer (ICT) processes upon photoexcitation, with the generated low-lying ICT state being the main deactivation channel from the locally excited state and, hence, ruling the fluorescence response. Noticeably, this response is modulated by the solvent polarity, and also by the bridge structure. Regarding this, BINOL- and BINAM-based bridges are found to promote an interesting unprecedented solvent-switchable dual emission from the ICT state with high Stokes shifts, triggering a significant bright red emission in less polar media.

Bis(haloBODIPYs) with Labile Helicity: Valuable Simple Organic Molecules That Enable Circularly Polarized Luminescence.

Simple organic molecules (SOM) based on bis(haloBODIPY) are shown to enable circularly polarized luminescence (CPL), giving rise to a new structural design for technologically valuable CPL-SOMs. The established design comprises together synthetic accessibility, labile helicity, possibility of reversing the handedness of the circularly polarized emission, and reactive functional groups, making it unique and attractive as advantageous platform for the development of smart CPL-SOMs.