Persistent radical anion polymers based on naphthalenediimide and a vinylene spacer

Persistent n-doped conjugated polymers were achieved by doping the electron accepting PDNDIV and PFNDIVpolymers with ionic (TBACN) or neutral (TDAE) dopants. The great electron affinities, as indicated by the low LUMO levels of PDNDIV (−4.09 eV) and PFNDIV (−4.27 eV), facilitated the chemical reduction from either TBACN or TDAE. The low-lying LUMOs of the neutral polymers PDNDIV and PFNDIV were achieved by incorporation of vinylene spacers between the electron poor NDI units to increase the conjugation length without the use of an electron donor, and this was lowered further by an electron-withdrawing fluorinated N-substituent on the NDI moiety. The polymer radical anions were found to persist for several days under ambient conditions by EPR spectroscopy. A distinguishing and noteworthy feature of these polymers is that they can be consecutively reduced by up to four electrons in acetonitrile. Conductivity measurements demonstrate the prospective impact of PDNDIV and PFNDIV for organic electronics

Selenium-Based Drug Development for Antioxidant and Anticancer Activity

Selenium is one of the eight necessary trace elements humans require for active health balance. It contributes in several ways to the proper functioning of selenoprotein. Selenium has received enormous interest recently due to its therapeutic potential against a number of ailments. To date, numerous chemical compounds containing selenium have been investigated for the therapy of cancer and other disorders. Unifying the selenium atom into chemical components (typically organic) greatly increased their bioactivities. We foresee that the structure–property relationship of recently developed materials could significantly decrease the laborious work of background research to achieve target-oriented drug design in coming years. This review summarizes the research progress in the last 10 to 15 years and the application of selenium-containing compounds in the design and synthesis of those materials for potential antioxidant and anticancer agents.</b

Theranostic Small-Molecule Prodrug Conjugates for Targeted Delivery and Controlled Release of Toll-like Receptor 7 Agonists

We previously reported the design and synthesis of a small-molecule drug conjugate (SMDC) platform that demonstrated several advantages over antibody–drug conjugates (ADCs) in terms of in vivo pharmacokinetics, solid tumor penetration, definitive chemical structure, and adaptability for modular synthesis. Constructed on a tri-modal SMDC platform derived from 1,3,5-triazine (TZ) that consists of a targeting moiety (Lys-Urea-Glu) for prostate-specific membrane antigen (PSMA), here we report a novel class of chemically identical theranostic small-molecule prodrug conjugates (T-SMPDCs), [18/19F]F-TZ(PSMA)-LEGU-TLR7, for PSMA-targeted delivery and controlled release of toll-like receptor 7 (TLR7) agonists to elicit de novo immune response for cancer immunotherapy. In vitro competitive binding assay of [19F]F-TZ(PSMA)-LEGU-TLR7 showed that the chemical modification of Lys-Urea-Glu did not compromise its binding affinity to PSMA. Receptor-mediated cell internalization upon the PSMA binding of [18F]F-TZ(PSMA)-LEGU-TLR7 showed a time-dependent increase, indicative of targeted intracellular delivery of the theranostic prodrug conjugate. The designed controlled release of gardiquimod, a TLR7 agonist, was realized by a legumain cleavable linker. We further performed an in vivo PET/CT imaging study that showed significantly higher uptake of [18F]F-TZ(PSMA)-LEGU-TLR7 in PSMA+ PC3-PIP tumors (1.9 ± 0.4% ID/g) than in PSMA− PC3-Flu tumors (0.8 ± 0.3% ID/g) at 1 h post-injection. In addition, the conjugate showed a one-compartment kinetic profile and in vivo stability. Taken together, our proof-of-concept biological evaluation demonstrated the potential of our T-SMPDCs for cancer immunomodulatory therapies

PSMA-Targeting Imaging and Theranostic Agents&mdash;Current Status and Future Perspective

In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents

Persistent radical anion polymers based on naphthalenediimide and a vinylene spacer.

Persistent n-doped conjugated polymers were achieved by doping the electron accepting PDNDIV and PFNDIV polymers with ionic (TBACN) or neutral (TDAE) dopants. The great electron affinities, as indicated by the low LUMO levels of PDNDIV (-4.09 eV) and PFNDIV (-4.27 eV), facilitated the chemical reduction from either TBACN or TDAE. The low-lying LUMOs of the neutral polymers PDNDIV and PFNDIV were achieved by incorporation of vinylene spacers between the electron poor NDI units to increase the conjugation length without the use of an electron donor, and this was lowered further by an electron-withdrawing fluorinated N-substituent on the NDI moiety. The polymer radical anions were found to persist for several days under ambient conditions by EPR spectroscopy. A distinguishing and noteworthy feature of these polymers is that they can be consecutively reduced by up to four electrons in acetonitrile. Conductivity measurements demonstrate the prospective impact of PDNDIV and PFNDIV for organic electronics

Cyclopenta[c]thiophene- and Diketopyrrolopyrrole-Based Red-Green-Blue Electrochromic Polymers

Abstract Cyclopenta[c]thiophene (CPT)-based polymers are potential candidates in organic electronics. Here, we report the first solution-processable red homopolymer (P1) of a thiophene-capped derivative of CPT (DHTCPT), and a blue homopolymer (P2) of N-substituted thienodiketopyrrolopyrrole (DEHTDPP). Additionally, by alternatingly copolymerizing the DHTCPT and DEHTDPP units, we achieved the green copolymer P3, thus completing the red-green-blue color wheels. We have shown experimentally and computationally (time-dependent density functional theory and natural bond orbital calculations) that P1 and P2 have very different optoelectronic features. However, in a donor–acceptor (D–A) copolymer P3, the optoelectronic properties have been tuned significantly to keep it in an intermediate range of P1 and P2. P2 and P3 absorb throughout the whole UV-vis range of the solar spectrum. Furthermore, all polymers showed electrochromism to switch colors between neutral and polaronic states in solution. For P1, the maximum optical contrast (%ΔT) was observed for the SOMO→LUMO transition, whereas P3 displayed the maximum %ΔT at the HOMO→LUMO transition

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer

After androgen deprivation therapy, a significant number of prostate cancer cases progress with a therapy-resistant neuroendocrine phenotype (NEPC). This represents a challenge for diagnosis and treatment. Based on our previously reported design of theranostic small-molecule prodrug conjugates (T-SMPDCs), herein we report a T-SMPDC tailored for targeted positron emission tomography (PET) imaging and chemotherapy of NEPC. The T-SMPDC is built upon a triazine core (TZ) to present three functionalities: (1) a chelating moiety (DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for PET imaging when labeled with 68Ga (t1/2 = 68 min) or other relevant radiometals; (2) an octreotide (Octr) that targets the somatostatin receptor 2 (SSTR2), which is overexpressed in the innervated tumor microenvironment (TME); and (3) fingolimod, FTY720—an antagonist of sphingosine kinase 1 that is an intracellular enzyme upregulated in NEPC. Polyethylene glycol (PEG) chains were incorporated via conventional conjugation methods or a click chemistry reaction forming a 1,4-disubstituted 1,2,3-triazole (Trz) linkage for the optimization of in vivo kinetics as necessary. The T-SMPDC, DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 (PEGn: PEG with n repeating ethyleneoxy units (n = 2, 3, or 4); Val: valine; Cit: citrulline; pABOC: p-amino-benzyloxycarbonyl), showed selective SSTR2 binding and mediated internalization of the molecule in SSTR2 high cells. Release of FTY720 was observed when the T-SMPDC was exposed to cathepsin B, and the released FTY720 exerted cytotoxicity in cells. In vivo PET imaging showed significantly higher accumulation (2.1 ± 0.3 %ID/g; p = 0.02) of [68Ga]Ga-DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 in SSTR2high prostate cancer xenografts than in the SSTR2low xenografts (1.5 ± 0.4 %ID/g) at 13 min post-injection (p.i.) with a rapid excretion through the kidneys. Taken together, these proof-of-concept results validate the design concept of the T-SMPDC, which may hold a great potential for targeted diagnosis and therapy of NEPC

An Efficient Molecular Tool with Ferrocene Backbone: Discriminating Fe³⁺ from Fe²⁺ in Aqueous Media

Two novel molecular probes with ferrocene backbone have been designed and synthesized for the first time, and they were subsequently found capable of distinguishing Fe³⁺ and Fe²⁺ ion in aqueous media. The discrimination of both the oxidation states (II/III) of iron by these receptors can be established either from a striking shift in redox potential (<b>1</b>: Δ<i>E</i>_1/2 ≈ 90 mV and <b>2</b>: Δ<i>E</i>_1/2 ≈ 59 mV) for Fe²⁺ ion or from UV–vis absorption studies (using light-absorption ratio variation approach (LARVA)). Moreover, the discrimination of Fe²⁺ and Fe³⁺ cations could be performed by naked-eye observation because of the development of different colors upon interaction with these probes which act as indicators for the in situ qualitative detection of Fe³⁺ and Fe²⁺. The limits of detection of Fe²⁺ and Fe³⁺ cations with receptor <b>2</b> were found to be as low as 30 and 15 parts per billion (ppb), respectively. The probable binding modes of these receptors with Fe²⁺ have also been suggested on the basis of the ¹H NMR spectroscopic titration, electrospray ionization mass spectrometry (ESI-MS), Job’s plot, and computational (DFT) studies along with electrochemical and spectro-photochemical data. Single crystal X-ray diffraction analysis of <b>1</b> revealed that its solid-state structure was stabilized via intermolecular C–H/O and O–H/N hydrogen bonds and by C–H/π interactions. Interestingly, detailed theoretical calculations (DFT) indicated that hydroxymethyl (−CH₂OH) group attached to naphthalene unit plays a pivotal role in sensing Fe²⁺/³⁺ ion selectively and in the stabilization of <b>2</b> in unusual eclipsed configuration through C–H···O type hydrogen bonding

Synthesis, Optoelectronic, and Transistor Properties of BODIPY- and Cyclopenta[<i>c</i>]thiophene-Containing π‑Conjugated Copolymers

Three new low-band-gap copolymers were synthesized by fusing dipyrromethene difluoroborane (BODIPY) as the acceptor (A) and thiophene-capped 5,5-bis­(hexyloxymethyl)-5,6-dihydro-4<i>H</i>-cyclopenta­[<i>c</i>]-thiophene (CPT) as the donor (D). The BODIPY unit was copolymerized through the ̀α′ positions (1 and 7 positions) in <b>P1</b> and through the ̀β′ positions (2 and 6 positions) in <b>P2</b> and <b>P3</b>. The additional acetylene unit between D and A in <b>P3</b> enhanced the conjugation by minimizing the possible steric hindrance compared to that in <b>P2</b>, whereas <b>P1</b> exhibited a more red-shifted absorption than <b>P2</b> and <b>P3</b> because of the more effective conjugaion through the ̀α′ positions of BODIPY. Importantly, the optical band gaps (<i>E</i>_g^opt) obtained from the onset of the absorption spectra are 1.28, 1.71, and 1.57 eV for <b>P1</b>, <b>P2</b>, and <b>P3</b>, respectively. <b>P1</b> has the lowest band gap for any CPT-containing polymer. In the best transistor devices, a mobility improvement by 4 orders of magnitude from 3.22 × 10^–6 cm² V^–1 s^–1 for <b>P2</b> to 0.01 cm² V^–1 s^–1 for <b>P1</b> was achieved. DFT calculations alongside measured charge-transport properties indicated that appreciable alterations in the optoelectronic properties of the polymers were achieved through minor changes in their structural features. The polymers were further characterized by thin-film X-ray diffraction, atomic force microscopy, and spectroelectrochemistry to investigate their material and electrochemical properties

Selenium-Containing Fused Bicyclic Heterocycle Diselenolodiselenole: Field Effect Transistor Study and Structure–Property Relationship

The first application of the diselenolodiselenole (C₄Se₄) heterocycle as an active organic field effect transistor materials is demonstrated here. C₄Se₄ derivatives (<b>2a</b>–<b>2d</b>) were obtained by using a newly developed straightforward diselenocyclization protocol, which includes the reaction of diynes with selenium powder at elevated temperature. C₄Se₄ derivatives exhibit strong donor characteristics and planar structure (except <b>2d</b>). The atomic force microscopic analysis and thin-film X-ray diffraction pattern of compounds <b>2a</b>–<b>2d</b> indicated the formation of distinct crystalline films that contain large domains. A scanning electron microscopy study of compound <b>2b</b> showed development of symmetrical grains with an average diameter of 150 nm. Interestingly, <b>2b</b> exhibited superior hole mobility, approaching 0.027 cm² V^–1 s^–1 with a transconductance of 9.2 μS. This study correlate the effect of π-stacking, Se···Se intermolecular interaction, and planarity with the charge transport properties and performance in the field effect transistor devices. We have shown that the planarity in C₄Se₄ derivatives was achieved by varying the end groups attached to the C₄Se₄ core. In turn, optoelectronic properties can also be tuned for all these derivatives by end-group variation