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TThe photovoltaic properties of binary and ternary blends of a polymer with molecular non-fullerene and fullerene acceptors are systematically investigated to provide morphology-charge dynamics–device performance design rules for future PSC development.

The ability to initialize an electron spin qubit into a well-defined state is an important criterion for quantum information applications. To achieve this goal, a chromophore photoexcited to its triplet state is used to strongly spin polarize a nearby stable radical in a series of C

Polar and polarizable π-conjugated organic molecules containing push-pull chromophores have been investigated extensively in the past. Identifying unique backbones and building blocks for fluorescent dyes is a timely exercise. Here, we report the synthesis and characterization of a series of fluorescent dyes containing quadrupolar A-D-A constitutions (where A = acceptor and D = donor), which exhibit fluorescence emission at a variety of different wavelengths. We have investigated the effects of different electron-withdrawing groups, located at both termini of a

Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers.

Supplemental Table 7. Targeting epigenetic resistance to BTK inhibitor treatment in ABC DLBCL, relates to Fig7

Supplemental Table 1. Epigenetic Ibrutinib Resistance in ABC DLBCL lines, , relates to Fig. 1

Supplemental Information- Figures & Legends (Supplemental Tables loaded separately)

Supplemental Table 6. RAC2 protein interactions are a marker of epigenetic ibrutinib resistance

Supplemental Table 4. Altered dependencies in ibrutinib resistant ABC DLBCL, relates to Fig. 4

Supplementary Methods

Supplemental Table2. Tracking the evolution of ibrutinib resistance phenotypes, relates to Fig. 2

Oligo and Primer Tables

Supplemental Table 5. RAC2 as a mediator of epigenetic ibrutinib resistance, , relates to Fig5

The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)–dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is a recurring problem. We modeled the development of resistance to the BTK inhibitor ibrutinib in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma, which relies on chronic active BCR signaling for survival. The primary mode of resistance was epigenetic, driven in part by the transcription factor TCF4. The resultant phenotypic shift altered BCR signaling such that the GTPase RAC2 substituted for BTK in the activation of phospholipase Cγ2, thereby sustaining NF-κB activity. The interaction of RAC2 with phospholipase Cγ2 was also increased in chronic lymphocytic leukemia cells from patients with persistent or progressive disease on BTK inhibitor treatment. We identified clinically available drugs that can treat epigenetic ibrutinib resistance, suggesting combination therapeutic strategies.Significance:In diffuse large B-cell lymphoma, we show that primary resistance to BTK inhibitors is due to epigenetic rather than genetic changes that circumvent the BTK blockade. We also observed this resistance mechanism in chronic lymphocytic leukemia, suggesting that epigenetic alterations may contribute more to BTK inhibitor resistance than currently thought.See related commentary by Pasqualucci, p. 555.This article is highlighted in the In This Issue feature, p. 549

Supplemental Table 3. Epigenetic retuning of oncogenic signaling in ibrutinib resistance, relates to Fig. 3

Vibronic coupling, the interplay of electronic and nuclear vibrational motion, is considered a critical mechanism in photoinduced reactions such as energy transfer, charge transfer, and singlet fission. However, our understanding of how particular vibronic couplings impact excited-state dynamics is lacking due to the limited number of experimental studies of model molecular systems. Herein, we use two-dimensional electronic spectroscopy (2DES) to launch and interrogate a range of vibronic coherences in two distinct types of perylenediimide slip stacks─along the short and long molecular axes, which form either an excimer or a mixed state between the Frenkel exciton (FE) and charge transfer states. We explore the functionality of these vibronic coherences using quantum beatmaps, which display the Fourier amplitude signal oscillations as a function of pump and probe frequencies, along with knowledge of the characteristic signatures of the FE, ionic, and excimer species. We find that a low-frequency vibrational mode of the short-axis slip stack appears concomitantly with the formation of the excimer state, survives 2-fold longer than in the FE state in the reference monomer, and shows a phase shift compared to other modes. For the long-axis slip stacks, a pair of low-frequency modes coupled to a high-frequency coordinate of the FE state were found to play a critical role in mixed-state generation. Our findings thus experimentally reveal the complex and varying roles of vibronic couplings in tightly packed multimers undergoing a range of photoinduced processes.

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells driven by B-cell receptor (BCR) signaling and activated primarily in the lymph node. The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib effectively inhibits BCR-dependent proliferation and survival signals and has emerged as a breakthrough therapy for CLL. However, complete remissions are uncommon and are achieved only after years of continuous therapy. We hypothesized that other signaling pathways that sustain CLL cell survival are only partially inhibited by ibrutinib. In normal B cells, Toll-like receptor (TLR) signaling cooperates with BCR signaling to activate prosurvival NF-κB. Here, we show that an experimentally validated gene signature of TLR activation is overexpressed in lymph node–resident CLL cells compared with cells in the blood. Consistent with TLR activation, we detected phosphorylation of NF-κB, STAT1, and STAT3 in lymph node–resident CLL cells and in cells stimulated with CpG oligonucleotides in vitro. CpG promoted IRAK1 degradation, secretion of IL10, and extended survival of CLL cells in culture. CpG-induced TLR signaling was significantly inhibited by both an IRAK1/4 inhibitor and ibrutinib. Although inhibition of TLR signaling was incomplete with either drug, the combination achieved superior results, including more effective inhibition of TLR-mediated survival signaling. Our data suggest an important role for TLR signaling in CLL pathogenesis and in sustaining the viability of CLL cells during ibrutinib therapy. The combination of ibrutinib with a TLR pathway inhibitor could provide superior antitumor activity and should be investigated in clinical studies.Significance:CLL relies on the concomitant cooperation of B-cell receptor and Toll-like receptor signaling; inhibition of both pathways is superior to inhibition of either pathway alone.

Supplementary Figure S1: Dose response experiments with the IRAK1/4 inhibitor (IRAKi) in CLL cells. Supplementary Figure S2: TLR signaling is active in lymph node-resident CLL cells. Supplementary Figure S3: Flow Cytometry gating strategy. Supplementary Figure S4: Early activation of STAT3 leads to early production of serum IL-10. Supplementary Figure S5: TLR signaling induces similar levels of IRAK1 degradation and STAT signaling in vitro with CpG stimulation in primary CLL PBMCs. Supplementary Figure S6: Upstream IRAK1 degradation and downstream phosphorylation of STAT3 and IκBα are inversely related. Supplementary Figure S7: CpG induced TLR signaling promotes cell survival and activates CLL cells in vitro. Supplementary Figure S8: Inhibiting induced TLR activation downregulates expression of activation markers and prevents the survival advantage in CLL cells. Supplementary Figure S9: αIgM stimulation induces activation of BCR pathway signaling. Supplementary Figure S10: Ibrutinib inhibits both BCR and TLR signaling in activated CLL cells harvested from the lymph node.

Supplementary Figure Legends S1-S10

Multiple myeloma is a common hematological malignancy of plasma cells, the terminally differentiated B cells that secrete antibodies as part of the adaptive immune response. Significant progress has been made in treating multiple myeloma, but this disease remains largely incurable, and most patients will eventually suffer a relapse of disease that becomes refractory to further therapies. Moreover, a portion of patients with multiple myeloma present with disease that is refractory to all treatments from the initial diagnosis, and no current therapeutic approaches can help. Therefore, the task remains to advance new therapeutic strategies to help these vulnerable patients. One strategy to meet this challenge is to unravel the complex web of pathogenic signaling pathways in malignant plasma cells and use this information to design novel precision medicine strategies to assist these patients most at risk.

Excimers usually serve as low energy trap sites in supramolecular chromophore assemblies; however, if the trap is not too deep, excimers may diffuse throughout the structure, making it possible to ...

Motion-induced change in emission (MICE) is a phenomenon that can be employed to develop various types of probes, including temperature and viscosity sensors. Although MICE, arising from the conformational motion in particular compounds, has been studied extensively, this phenomenon has not been investigated in depth in mechanically interlocked molecules (MIMs) undergoing coconformational changes. Herein, we report the investigation of a thermoresponsive dynamic homo[2]catenane incorporating pyrene units and displaying relative circumrotational motions of its cyclophanes as evidenced by variable-temperature

Photoexcited organic chromophores appended to stable radicals can serve as qubit and/or qudit candidates for quantum information applications. 1,6,7,12-Tetra-(4-tert-butylphenoxy)-perylene-3,4 : 9,10-bis(dicarboximide) (tpPDI) linked to a partially deuterated α,γ-bisdiphenylene-β-phenylallyl radical (BDPA-d

The mechanism of spin polarization transfer from a photogenerated spin-correlated radical pair to a stable radical was studied in a covalent donor-chromophore-acceptor-stable radical (D-C-A-R•) system, where the donor (D) is 4-methoxyaniline (MeOAn), the chromophore (C) is 4-(N-piperidinyl)-naphthalene-1,8-dicarboximide (ANI), the acceptor (A) is naphthalene-1,8:4,5-bis(dicarboximide) (NDI) and the stable radical (R•) is (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO). Experiments probed the effect of the spin–spin exchange interaction between D•+ and A•− as well as the charge recombination dynamics of D•+-C-A•− on spin polarization transfer from the D•+-C-A•− SCRP to R• as a function of the dielectric environment in glassy media at cryogenic temperatures. The results show that spin polarization on R• is generated by asymmetry in the charge recombination pathways rather than variations in the spin–spin exchange interaction between D•+ and A•−. These results inform design criteria for using an SCRP to spin polarize a third spin for potential applications in quantum information science.

Here, we report an approach to the synthesis of highly charged enantiopure cyclophanes by the insertion of axially chiral enantiomeric binaphthyl fluorophores into the constitutions of pyridinium-based macrocycles. Remarkably, these fluorescent tetracationic cyclophanes exhibit a significant AIE compared to their neutral optically active binaphthyl precursors. A combination of theoretical calculations and time-resolved spectroscopy reveal that the AIE originates from limited torsional vibrations associated with the axes of chirality present in the chiral enantiomeric binaphthyl units and the fine-tuning of their electronic landscape when incorporated within the cyclophane structure. Furthermore, these highly charged enantiopure cyclophanes display CPL responses both in solution and in the aggregated state. This unique duality of AIE and CPL in these tetracationic cyclophanes is destined to be of major importance in future development of photonic devices and bio-applications., National Science Foundation (NSF) DMR-2003739, United States Department of Energy (DOE) DE-SC0000989, SHyNE Resource NSF ECCS-2025633, IIN, Northwestern's MRSEC program NSF DMR-1720139, MCIN/AIE EQC2019-006543-P, ERDF A way of making Europe, FEDER(ERDF)/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P18-FR-2877

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, Duva florida, were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (1), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation. The absolute stereochemistry was determined through vibrational circular dichroism. Functional biochemical assays and in silico docking experiments found tuaimenal A selectively inhibits the viral main protease (3CLpro) of SARS-CoV-2.

Covalent chromophore dimers having the required energetics can undergo intramolecular singlet fission (SF) in solution; however, in the solid state, intra- and intermolecular SF can compete. Here, ...

Although catenanes comprising two ring-shaped components can be made in large quantities by templation, the preparation of three-dimensional (3D) catenanes with cage-shaped components is still in its infancy. Here, we report the design and syntheses of two 3D catenanes by a sequence of SN2 reactions in one pot. The resulting triply mechanically interlocked molecules were fully characterized in both the solution and solid states. Mechanistic studies have revealed that a suit[3]ane, which contains a threefold symmetric cage component as the suit and a tribromide component as the body, is formed at elevated temperatures. This suit[3]ane was identified as the key reactive intermediate for the selective formation of the two 3D catenanes which do not represent thermodynamic minima. We foresee a future in which this particular synthetic strategy guides the rational design and production of mechanically interlocked molecules under kinetic control.