Insights into the photoinduced anion translocation of donor-π-acceptor (ion) molecules.

By strategic design and synthesis of a new series of phosphonium salts (compounds 1-7[OTf]), where [OTf] stands for the trifluoromethanesulfonate anion, we performed comprehensive spectroscopic and dynamic studies on the photoinduced anion migration in toluene. Our aim is to probe if the anion migration is associated with an intrinsic barrier or is barrier-free. After the occurrence of excited-state intramolecular charge transfer (ESICT) in 1-7, the charge redistribution of the cation triggers the translocation of the counter anion [OTf], resulting in emission spectral temporal evolution.

Light Induced Proton Coupled Charge Transfer Triggers Counterion Directional Translocation.

We demonstrate directed translocation of ClO anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction.

Hydrogen-Bonded Thiol Undergoes Unconventional Excited-State Intramolecular Proton-Transfer Reactions.

The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone () undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant π* character of the tautomeric lowest excited state.

Long-range hydrogen-bond relay catalyses the excited-state proton transfer reaction.

Solvent (, water)-catalyzed proton transfer (SCPT) the relay of hydrogen (H)-bonds plays a key role in proton migration. In this study, a new class of 1-pyrrolo[3,2-]quinolines (PyrQs) and their derivatives were synthesized, with sufficient separation of the pyrrolic proton donating and pyridinic proton accepting sites to probe excited-state SCPT. There was dual fluorescence for all PyrQs in methanol, , normal (PyrQ) and tautomer 8-pyrrolo[3,2]quinoline (8H-PyrQ) emissions.

A highly efficient transgene knock-in technology in clinically relevant cell types.

Inefficient knock-in of transgene cargos limits the potential of cell-based medicines. In this study, we used a CRISPR nuclease that targets a site within an exon of an essential gene and designed a cargo template so that correct knock-in would retain essential gene function while also integrating the transgene(s) of interest. Cells with non-productive insertions and deletions would undergo negative selection.

Rational Design of Asymmetric Polymethines to Attain NIR(II) Bioimaging at >1100 nm.

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λ play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores.

Comprehensive Thione-Derived Perylene Diimides and Their Bio-Conjugation for Simultaneous Imaging, Tracking, and Targeted Photodynamic Therapy.

In this study, the chromophore 3,4,9,10-perylenetetracarboxylic diimide (PDI) is anchored with phenyl substituents at the imide N site, followed by thionation, yielding a series of thione products , , , , and , respectively, with = 1, 2, 3, and 4 thione. The photophysical properties are dependent on the number of anchored thiones, where the observed prominent lower-lying absorption is assigned to the S → S(ππ*) transition and is red-shifted upon increasing the number of thiones; the lowest-lying excited state is ascribed to a transition-forbidden S(π*) configuration. All s are non-emissive in solution but reveal an excellent two-photon absorption cross-section of >800 GM.

A new approach exploiting thermally activated delayed fluorescence molecules to optimize solar thermal energy storage.

We propose a new concept exploiting thermally activated delayed fluorescence (TADF) molecules as photosensitizers, storage units and signal transducers to harness solar thermal energy. Molecular composites based on the TADF core phenoxazine-triphenyltriazine (PXZ-TRZ) anchored with norbornadiene (NBD) were synthesized, yielding compounds PZDN and PZTN with two and four NBD units, respectively. Upon visible-light excitation, energy transfer to the triplet state of NBD occurred, followed by NBD → quadricyclane (QC) conversion, which can be monitored by changes in steady-state or time-resolved spectra.

Energy Counterbalance to Harness Photoinduced Structural Planarization of Dibenzo[]azepines toward Thermal Reversibility.

In sharp contrast to most photoinduced structural planarization (PISP) phenomena, which are highly exergonic and irreversible processes, we report here a series of a new class of PISP molecules, 9-phenyl-9-tribenzo[]azepine () and its derivatives, where PISP is within the thermally reversible regime. The underlying foundation is the energy counterbalance along PISP, where upon electronic excitation the azepine core chromophore undergoes planarization to gain stabilization from a cyclic 4 π conjugation ( is an integer; Baird's rule). Concurrently, the C═C fused benzene ring is prone to gain aromaticity, which conversely decreases the 4 π-electron resonance stabilization of the 9-tribenzo[]azepine, hindering a full planarization.

Functionalizing Collagen with Vessel-Penetrating Two-Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia.

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (Re ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, Re -diimine complex already exhibits excellent emission yield (34%, λ   = 583 nm) and large two-photon absorption cross-sections (σ   = 300 GM @ 800 nm) in water (pH 7.

Cyano Derivatives of 7-Aminoquinoline That Are Highly Emissive in Water: Potential for Sensing Applications.

6-Cyano-7-aminoquinoline (6CN-7AQ) and 3-cyano-7-aminoquinoline (3CN-7AQ) were synthesized and found to exhibit intense emission with quantum yield as high as 63 % and 85 %, respectively, in water. Conversely, their derivatives 6-cyano-7-azidoquinoline (6CN-7N Q) and 3-cyano-7-azidoquinoline (3CN-7N Q) show virtually no emission, which makes them suitable to be used as recognition agents in azide reactions based on fluorescence recovery. Moreover, conjugation of 6CN-7AQ with a hydrophobic biomembrane-penetration peptide PFVYLI renders a nearly non-emissive 6CN-7AQ-PFVYLI composite, which can be digested by proteinase K, recovering the highly emissive 6CN-7AQ with ∼200-fold enhancement.

Fluorescence Probes Exhibit Photoinduced Structural Planarization: Sensing and Microscopic Dynamics of Viscosity Free from Polarity Interference.

We demonstrate the construction of wavelength λ-ratiometric images that allow visualizing the distribution of microscopic dynamics within living cells and tissues by using the newly developed principle of fluorescence response. The bent-to-planar motion in the excited state of incorporated fluorescence probes leads to elongation of the π-delocalization, resulting in microviscosity-dependent but polarity-insensitive interplay between well-separated blue and red bands in emission spectra. This allows constructing the exceptionally contrasted images of cellular dynamics.

Mono-Heteroatom Substitution for Harnessing Excited-State Structural Planarization of Dihydrodibenzo[a,c]phenazines.

With the aim of generalizing the structure-properties relationship of bending heterocyclic molecules that undergo prominent photoinduced structural planarization (PISP), a series of new dihydrodibenzo[ac]phenazine derivatives in which one nitrogen atom is replaced by oxygen (PNO), sulfur (PNS), selenium (PNSe), or dimethylmethanediyl (PNC) was strategically designed and synthesized. Compounds PNO, PNS, and PNSe have significantly nonplanar geometries in the ground state, which undergo PISP to give a planarlike conformer and hence a large emission Stokes shift. A combination of femtosecond early relaxation dynamics and computational approaches established an R*→I* (intermediate)→P* sequential kinetic pattern for PNS and PNSe, whereas PNO undergoes R*→P* one-step kinetics.

Catalytic-Type Excited-State N-H Proton-Transfer Reaction in 7-Aminoquinoline and Its Derivatives.

7-Aminoquinoline (7AQ) and various amino derivatives thereof (-NHR) have been strategically designed and synthesized to study their excited-state proton-transfer (ESPT) properties. Due to the large separation between the proton donor -NHR and the acceptor -N- site, ESPT in 7AQ derivatives, if available, should proceed under protic solvent catalysis. ESPT is found to be influenced by the acidity of -NHR and the basicity of the proton-acceptor -N- in the quinoline moiety.

Indeno[1,2-b]fluorene-Based [2,2]Cyclophanes with 4n/4n and 4n/[4n+2] π Electrons: Syntheses, Structural Analyses, and Excitonic Coupling Properties.

Indeno[1,2-b]fluorene-based [2,2]cyclophanes with 4n/4n and 4n/[4n+2] π-electron systems were prepared, and their structures were identified by X-ray crystallography. With short π-π distances around 3.0 Å, [2.

Diindeno-Fused Dibenzo[a,h]anthracene and Dibenzo[c,l]chrysene: Syntheses, Structural Analyses, and Properties.

Diindeno-fused dibenzo[a,h]anthracene 6 and diindeno-fused dibenzo[c,l]chrysene 9 contain the key moieties 1,4-quinodipropene (1,4-QDP) and 2,6-naphthoquinodipropene (2,6-NQDP), respectively, and they both have an open-shell singlet ground state. The latter compound exhibits a strong biradical character and interesting properties, including a low ΔE (2.44 kcal mol ), a small HOMO-LUMO gap (1.

Long-Term Engraftment and Fetal Globin Induction upon Gene Editing in Bone-Marrow-Derived CD34 Hematopoietic Stem and Progenitor Cells.

To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34 hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of resulting from bi-allelic frameshift mutations in exon 2 adversely affected erythroid enucleation.

Functional footprinting of regulatory DNA.

Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements.

A comparative encyclopedia of DNA elements in the mouse genome.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Transcriptome dynamics during human erythroid differentiation and development.

To explore the mechanisms controlling erythroid differentiation and development, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human embryonic stem cells (HESCs) into the erythroid lineage and development of embryonic to adult erythropoiesis using high throughput sequencing technology. HESCs and erythroid cells at three developmental stages: ESER (embryonic), FLER (fetal), and PBER (adult) were analyzed. Our findings revealed that the number of expressed genes decreased during differentiation, whereas the total expression intensity increased.

Transcriptional environment and chromatin architecture interplay dictates globin expression patterns of heterospecific hybrids derived from undifferentiated human embryonic stem cells or from their erythroid progeny.

To explore the response of β globin locus with established chromatin domains upon their exposure to new transcriptional environments, we transferred the chromatin-packaged β globin locus of undifferentiated human embryonic stem cells (hESCs) or hESC-derived erythroblasts into an adult transcriptional environment. Distinct globin expression patterns were observed. In hESC-derived erythroblasts where both ε and γ globin were active and marked by similar chromatin modifications, ε globin was immediately silenced upon transfer, whereas γ globin continued to be expressed for months, implying that different transcriptional environments were required for their continuing expression.

Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors.

Background: Mapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identify cis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors.