Naphthalene diimide-Annulated Heterocyclic Acenes: Synthesis, Electrochemical and Semiconductor Properties and their Multifaceted Applications.

Acenes and Naphthalene Diimides (NDIs) stand as distinguished classes of organic compounds, each possessing unique and intriguing properties that have garnered significant attention across various scientific disciplines. Acenes, characterized by linearly fused aromatic rings, have captivated researchers due to their diverse electronic structures and promising applications in materials science. On the other hand, NDIs, known for their distinctive electron-accepting properties, exhibit remarkable versatility in fields ranging from organic electronics, supramolecular to spin chemistry. In this review, we navigate through the fascinating realms of both acenes and NDIs before converging our focus on the highly diverse and distinctive subgroup of NDI-annulated heterocyclic acenes. This potentially important subgroup, has emerged as a subject of intense investigation, encapsulating their fascinating synthesis, optical and electrochemical characteristics, and multifaceted applications that span the realms of chemistry, physics, and biology. Through the exploration of their synthetic strategies, unique properties, and diverse applications, this review aims to offer a comprehensive understanding of the pivotal role played by NDI-based heterocyclic acenes in contemporary multidisciplinary research and technological innovation.

A folded π-system with supramolecularly oriented dipoles: single-component piezoelectric relaxor with NLO activity.

Organic molecules with an active dipole moment have a natural propensity to align in an antiparallel fashion in the solid state, resulting in zero macroscopic polarization. This primary limitation makes the material unresponsive to switching with electric fields, mechanical forces, and to intense laser light. A single-component organic material that bestows macroscopic dipole-driven electro-mechanical and optical functions, e.g., piezoelectric, ferroelectric and nonlinear optical (NLO) activity, is unprecedented due to the design challenges imparted by crystal symmetry and dipole orientations. Herein we report a crystalline organic material that self-assembles with a polar order (P 1), and is endowed with a high piezoelectric coefficient (d 33-47 pm V-1), as well as ferroelectric and Debye-type relaxor properties. In addition, it shows second harmonic generation (SHG) activity, which is more than five times that of the benchmark potassium dihydrogen phosphate. Piezoelectric force microscopy (PFM) images validated electro-mechanical deformations. Piezoresponse force spectroscopy (PFS) studies confirmed a signature butterfly-like amplitude and a phase loop. To the best of our knowledge, this is the first report of a folded supramolecular π-system that manifests unidirectionally oriented dipoles and exhibits piezoelectricity, ferroelectricity, and has excellent ability to generate second harmonic light. These findings can herald new design possibilities based on folded architectures to explore opto-, electro- and mechano-responsive multifaceted functions.

A highly contorted push-pull naphthalenediimide dimer and evidence of intramolecular singlet exciton fission.

Singlet fission is a process by which two molecular triplet excitons are generated subsequent to the absorption of one photon. Molecules that enable singlet fission have triplet state energy at least half of the bright singlet state energy. This stringent energy criteria have challenged chemists to device new molecular and supramolecular design principles to modulate the singlet-triplet energy gap and build singlet fission systems from a wide range of organic chromophores. Herein, we report for the first time intramolecular singlet fission in the seminal naphthalenediimide (NDI) scaffold constrained in a push-pull cyclophane architecture, while individually the NDI chromophore does not satisfy the energy criterion. The challenging synthesis of this highly contorted push-pull cyclophane is possible from the preorganized pincer-like precursor. The special architecture establishes the shortest co-facial NDI⋯NDI contacts (3.084 Å) realized to date. Using broadband femtosecond transient absorption, we find that the correlated T-T pair forms rapidly within 380 fs of photoexcitation. Electronic structure calculations at the level of state-averaged CASSCF (ne,mo)/XMCQDPT2 support the existence of the multi-excitonic T-T pair state, thereby confirming the first example of singlet exciton fission in a NDI scaffold.

Synthesis of a Highly Electron-Deficient, Water-Stable, Large Ionic Box: Multielectron Accumulation and Proton Conductivity.

π-acidic boxes exhibiting electron reservoir and proton conduction are unprecedented because of their instability in water. We present the synthesis of one of the strongest electron-deficient ionic boxes showing e- uptake as well as proton conductivity. Two large anions fit in the box to form anion-π interactions and form infinite anion-solvent wires. The box with NO3-···water wires confers high proton conductivity and presents the first example that manifests redox and ionic functionality in an organic electron-deficient macrocycle.

DNA damage, cell cycle perturbation and cell death by naphthalene diimide derivative in gastric cancer cells.

Stomach cancer causes the third-highest cancer-related deaths worldwide. Limited availability of anticancer measures with higher efficiency and low unwanted toxicities necessitates the development of better cancer chemotherapeutics. Naphthalene diimide (NDI) derivatives have gained significant attention owing to their excellent anticancer potential. We evaluated the anticancer properties of NDI derivatives, 1a and 2a in cancer cell lines and found that 1a showed higher efficacy as compared to 2a exhibiting a remarkable difference in activity upon single atom substitution of C with N. Particularly, NDI 1a showed potent inhibitory activity against gastric cancer cell line AGS with IC50 of 2.0 µM. NDI 1a induced remarkable morphological changes and reduced clonogenicity as well as the migratory ability of AGS cells. The reduction in AGS cell migration was mediated through inhibition of Tyr397 p-FAK dephosphorylation at focal adhesion points leading to enhanced attachment of cells at contact points. NDI 1a caused extensive DNA double-strand-breaks (DSBs) leading to activation of p53 and its transcriptional target p21. Reduced nuclear BRCA1 but enhanced nuclear p53BP1 foci formation upon 1a treatment suggests that DNA DSB repair is mediated through error-prone NHEJ which led to the accumulation of extensive DNA damage. Combinatorial effects mediated by interactions of 1a with double-stranded DNA through minor groove binding as well as induction of intracellular ROS exacerbated the loss of genomic integrity induced by 1a. NDI 1a mediated DNA damage-induced S phase arrest; however, cells experiencing extensive and irreparable DNA damage underwent mitochondrial apoptosis through downregulation of anti-apoptotic protein p21. Furthermore, proliferation inhibitory activity of 1a is also attributed to inhibition of ß-catenin/c-Myc axis in AGS cells with constitutively active ß-catenin pathway. In vivo toxicity analysis of 1a revealed minimal systemic toxicity suggesting that compound 1a is a safe and potential candidate for the development of gastric cancer chemotherapeutics.

Naphthalenediimides with High Fluorescence Quantum Yield: Bright-Red, Stable, and Responsive Fluorescent Dyes.

The naphthalenediimide (NDI) scaffold in contrast to its higher congeners possess low-fluorescence. In spite of elegant synthetic developments, a highly emissive NDI is quite rare to find, as well as, a green-light-emitting NDI is yet to be explored. Herein, we report a novel class of symmetric and asymmetric NH2 -substituted core-NDIs (1-5) with tunable fluorescence in the visible region and extending to the NIR frontier. Importantly, the bis-NH2 -substituted NDI 2 revealed quantum yield, Φ f of ≈81 and ≈68 % in toluene and DMSO, respectively, suggesting versatility of the fluorophore in a wide range of solvent polarity. The dye 1 is shown to be the first NDI-based green-light emitter. The donor piperidine group in 5 diminish the Φ f by 40-fold providing a lever to modulate the excited-state intramolecular proton transfer (ESIPT) process. Our synthetic protocol applies a Pd catalyst and a benign hydride source simplifying the non-trivial -NH2 group integration at the NDI-core. TD-DFT calculations predicted strong intramolecular hydrogen bonds in the excited state in the bulk nonpolar medium and responsiveness to solvent polarity. The maximization of the NDI emission outlined here would further boost the burgeoning repertoire of applications of the NDI scaffold.

Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity.

Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacin-based hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 ± 1.2 nM and 25.52 ± 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 µM and 1 µM, respectively.

Synthesis of Stable, High-SOMO Zwitterionic Radicals: Enabling Intermolecular Electron Transfer between Naphthalenediimides.

Synthesis to enhance the electron donor ability of organic radicals has not been attempted due to reactivity challenges. Herein, naphthalenediimide-based (NDI•±) zwitterionic radicals are synthesized and isolated bestowing SOMO levels up to -4.04 eV. As a result, reduction of the NDI is realized with NDI•± radicals in their ground states. Notably, reduction of the NDI unit applying a π-electron donor is unprecedented and has been limited to inorganic/organometallic reagents or by light-driven excited states.

Halogen-Bonded Assemblies of Arylene Imides and Diimides: Insight from Electronic, Structural, and Computational Studies.

Halogen-bonding interactions in electron-deficient π scaffolds have largely been underexplored. Herein, the halogen-bonding properties of arylene imide/diimide-based electron-deficient scaffolds were studied. The influence of scaffold size, from small (phthalimide) to moderately sized (pyromellitic diimide or naphthalenediimides) to large (perylenediimide), axial-group modification, and number of halo substituents on the halogen bonding and its self-assembly was probed in a set of nine compounds. The structural modification leads to tunable optical and redox properties. The first reduction potential E 1 / 2 1 ranges between -1.09 and -0.17 V (vs. SCE). Two of the compounds, that is, 6 and 9, have deep-lying LUMOs with values reaching -4.2 eV. Single crystals of all nine systems were obtained, which showed Br⋅⋅⋅O, Br⋅⋅⋅Br, or Br⋅⋅⋅π halogen-bonding interactions, and a few systems are capable of forming all three types. These interactions lead to halogen-bonded rings (up to 12-membered), which propagate to form stacked 1D, 2D, or corrugated sheets. A few outliers were also identified, for example, molecules that prefer C-H⋅⋅⋅O hydrogen bonding over halogen bonding, or noncentrosymmetric rather than centrosymmetric organization. Computational studies based on Atoms in Molecules and Natural Bond Orbital analysis provided further insight into the halogen-bonding interactions. This study can lead to a predictive design tool-box to further explore related systems on surfaces reinforced by these weak directional forces.

Molecular and Supramolecular Multiredox Systems.

The design and synthesis of molecular and supramolecular multiredox systems have been summarized. These systems are of great importance as they can be employed in the next generation of materials for energy storage, energy transport, and solar fuel production. Nature provides guiding pathways and insights to judiciously incorporate and tune the various molecular and supramolecular design aspects that result in the formation of complex and efficient systems. In this review, we have classified molecular multiredox systems into organic and organic-inorganic hybrid systems. The organic multiredox systems are further classified into multielectron acceptors, multielectron donors and ambipolar molecules. Synthetic chemists have integrated different electron donating and electron withdrawing groups to realize these complex molecular systems. Further, we have reviewed supramolecular multiredox systems, redox-active host-guest recognition, including mechanically interlocked systems. Finally, the review provides a discussion on the diverse applications, e. g. in artificial photosynthesis, water splitting, dynamic random access memory, etc. that can be realized from these artificial molecular or supramolecular multiredox systems.

Doubly zwitterionic, di-reduced, highly electron-rich, air-stable naphthalenediimides: redox-switchable islands of aromatic-antiaromatic states.

The di-reduced state of the naphthalene moiety and its congeners have long captivated chemists as it is elusive to stabilize these intrinsically reactive electron-rich π-systems and for their emergent multifaceted properties. Herein we report the synthesis and isolation of two-electron (2e-) reduced, highly electron-rich naphthalenediimides (NDIs). A doubly zwitterionic structure is observed for the first time in a naphthalene moiety and validated by single crystal X-ray crystallography and spectroscopic methods. The synthesis avoids hazardous reducing agents and offers an easy, high-yielding route to bench-stable di-reduced NDIs. Notably, we realized high negative first oxidation potentials of up to -0.730 V vs. Fc/Fc+ in these systems, which establish these systems to be one of the strongest ambient stable electron donors. The study also provides the first insights into the NMR spectra of the di-reduced systems revealing a large decrease in diatropicity of the naphthalene ring compared to its 2e- oxidized form. The NICS, NICS-XY global ring current, gauge-including magnetically induced current (GIMIC) and AICD ring current density calculations revealed switching of the antiaromatic and aromatic states at the naphthalene and the imide rings, respectively, in the di-reduced system compared to the 2e- oxidized form. Notably, the substituents at the phosphonium groups significantly tune the antiaromatic-aromatic states and donor ability, and bestow an array of colors to the di-reduced systems by virtue of intramolecular through-space communication with the NDI scaffold. Computational studies showed intramolecular noncovalent interactions to provide additional stability to these unprecedented doubly zwitterionic systems.

Synthesis and Isolation of a Stable Perylenediimide Radical Anion and Its Exceptionally Electron-Deficient Precursor.

The synthesis and isolation of an ambient stable perylenediimide radical anion is reported, and its precursor is established as one of the strongest electron acceptors. The radical anion shows absorption up to 1400 nm and is stable in mixed aqueous solution. Interestingly, the radical anion can organize two electron-deficient molecules over its surface to form a π-stacked array. Calculations revealed weak spin polarization via noncovalent interactions. Such interactions are of significance for magnetic exchange and catalysis.

Downregulation of c-Myc and p21 expression and induction of S phase arrest by naphthalene diimide derivative in gastric adenocarcinoma cells.

Naphthalene diimide (NDI) derivatives have been shown to exhibit promising antineoplastic properties. In the current study, we assessed the anticancer and anti-bacterial properties of di-substituted NDI derivative. The naphthalene-bis-hydrazimide, 1, negatively affected the cell viability of three cancer cell lines (AGS, HeLa and PC3) and induced S phase cell cycle arrest along with SubG0/G1 accumulation. Amongst three cell lines, gastric cancer cell line, AGS, showed the highest sensitivity towards the NDI derivative 1. Compound 1 induced extensive DNA double strand breaks causing p53 activation leading to transcription of p53 target gene p21 in AGS cells. Reduction in protein levels of p21 and BRCA1 suggested that 1 treated AGS cells underwent cell death due to accumulation of DNA damage as a result of impaired DNA damage repair. ß-catenin downregulation and consequently decrease in levels of c-Myc may have led to 1 induced AGS cell proliferation inhibition.1 induced AGS cell S phase arrest was mediated through CylinA/CDK2 downregulation. The possible mechanisms involved in anticancer activity of 1 includes ROS upregulation, induction of DNA damage, disruption of mitochondrial membrane potential causing ATP depletion, inhibition of cell proliferation and downregulation of antiapoptotic factors ultimately leading to mitochondria mediated apoptosis. Further compound 1 also inhibited H. pylori proliferation as well as H. pylori induced morphological changes in AGS cells. These findings suggest that NDI derivative 1 exhibits two-pronged anticancer activity, one by directly inhibiting cancer cell growth and inducing apoptosis and the other by inhibiting H. pylori.

Ionic Assembly, Anion-π, Magnetic, and Electronic Attributes of Ambient Stable Naphthalenediimide Radical Ions.

Organic spin-based molecular materials are considered to be attractive for the generation of functional materials with emergent optoelectronic, magnetic, or magneto-conductive properties. However, the major limitations to the utilization of organic spin-based systems are their high reactivity, instability, and propensity for dimerization. Herein, we report the synthesis, characterization, and magnetic and electronic studies of three ambient stable radical ions (1 a.+ , 1 b.+ , and 1 c.+ ). The radical ions 1 b.+ and 1 c.+ with BPh4 - and BF4 - counter anions, respectively, were synthesized in excellent yields by means of anion metathesis of 1 a.+ with Br- as its counter anion. Notably, synthesis of 1 a.+ was achieved in an ecofriendly, solvent-free protocol. The radical ions were characterized by means of single-crystal X-ray diffraction studies, which revealed the discrete nature of the radical ions and extensive hydrogen-bonding interactions within the radical ions and with the counter anions. Thus, radical ions can be organized to form infinite supramolecular arrays using weak noncovalent interactions. In addition, the Br- , BF4 - , and BPh4 - anions formed diverse types of anion-π interactions with the naphthalene and imide rings of the radical ions. The radical ions were characterized by means of X-band electron paramagnetic resonance (EPR) spectroscopy in solution and in the solid state. Magnetic studies revealed their paramagnetic nature in the range of 10 to 300 K. The radical ions exhibited high resistivity approaching the gigaohm (GΩ) scale. In addition, the radical ions exhibited panchromism.

Buchwald-Hartwig Coupling at the Naphthalenediimide Core: Access to Dendritic, Panchromatic NIR Absorbers with Exceptionally Low Band Gap.

The first successful Buchwald-Hartwig reaction at the naphthalenediimide core is reported, leading to the coupling of diverse secondary aromatic amines including dendritic donors. The G1-dendrimer-based donor exhibit blackish color, providing access to black absorbing systems. λonset values up to 1070 nm was achieved, which is the maximum from a single NDI scaffold. These dyes also manifest multielectron reservoir properties. A total of eight-redox states with a band gap of ∼0.95 eV was accomplished.

Isolation of Tetracyano-Naphthalenediimide and Its Stable Planar Radical Anion.

Reported herein is the first isolation of tetracyano-naphthalenediimide [NDI(CN)4 ] and its radical anion, and structural elucidation through spectroscopic and X-ray diffraction studies. The radical anion shows remarkable stability and was purified by chromatography, which is unique for planar radical anions. The stability results from multiple hydrogen bonds to the counter ion and through an array of intramolecular noncovalent interactions. The radical anion revealed one of the strongest NDI π-π interactions (3.268 Å). Electrochemical studies of [NDI(CN)4 ] confirm its extraordinarily low-lying LUMO (-5.0 eV), rendering it one of the strongest electron-deficient planar π systems to be isolated. The manifold potential, which remained unknown to date, can now be explored for these open- and closed-shell planar π systems.

Electron sponge from naphthalenediimide-viologen conjugates: water-stable, highly electron-deficient polyions with 1 V potential window.

We report a new class of multi-electron acceptors by integrating for the first time multiple π-cations at the naphthalenediimide-core. These polyions present a remarkably low-lying LUMO with water stability, seven-redox states in a narrow window of ∼1 V and excellent reversibility. Extended conjugation is manifest in mixed valence states with NIR absorption. X-ray crystallography revealed appealing multiple anion-π interactions.

Appending Diverse π-Extended Acceptors with Tetrathiafulvalene/Dithiafulvalene Donors: Multistate Redox Properties, Radical Ion Generation, and Mid-IR-Absorbing Mixed-Valence States.

Three classes of donor-acceptor (D-A) π-extended chromophores (1-12) were synthesized through a phosphite-mediated cross-coupling reaction, in which the anhydride- or imide-based π-As and number of tetrathiafulvalene (TTF)/dithiafulvalene (DTF) Ds were systematically changed. Large π rings, such as benzoperylene and coronene, were integrated into the TTF/DTF unit, for the first time, to overcome their high insolubility. The anhydride and imide groups in the π acceptors can significantly alter the frontier orbitals and influence the optoelectronic properties. The D moieties allow the formation of radical cations (D.+ ) and the π-extended A moieties aid the formation of radical anions (A.- ) by oxidation/reduction under ambient conditions. The molecules revealed UV/Vis/near-IR absorption, fluorescence extending into the near-IR region, and amphoteric electrochemical properties. Chromophores 10 and 12 show solvatochromism in a wide range of solvents. The π-As with anhydride functionality allow easier electron uptake, relative to the imide groups, whereas the increasing number of D TTF/DTF units make them easy to oxidize. Interestingly, the trans-TTF-fused molecules (1, 6, and 11) exhibited a mixed-valence state in the mid-IR region (ν˜ =5130-4000 cm-1 ). Moderate electron coupling between the redox centers is inferred to the compounds being of Robin-Day class II. The multistate redox activity along with panchromism and near-/mid-IR optical absorption of these systems can be attractive towards advanced switchable materials.

Ambient Water-Stable Dianionic Electron Donors: Intramolecular Noncovalent Conduits Assist Charge Delocalization.

Electron-rich π-conjugated dianions are known to be ambient unstable and their stabilization in ambient water is yet to be realized. We report the first example of an exceptionally stable naphthalenediimide-based dianion in ambient and hot water, forming one of the most stable redox-active dianion. The half-life (t1/2 ) of dianion (1 a2- ) is more than four months in ambient water. The dianionic state was confirmed by X-ray crystallography and by various spectroscopic methods. The noncovalent electronic conduits introduced for the first time in dianions, embrace nO →π*C≡N interactions and aid in delocalizing the dianionic charge as validated from theoretical studies. The dianions harness strong NIR absorption and electron donor ability to organic acceptors and metal ions, which make them suitable for potential green energy applications.

Synthesis of Octabromoperylene Dianhydride and Diimides: Evidence of Halogen Bonding and Semiconducting Properties.

A facile synthesis of octabromoperylene-3,4,9,10-tetracarboxylic dianhydride (Br8-PDA) (1), its diimides (Br8-PDIs) (2a-e), and bis-, tris-, and tetra-amino substituted diimides (5a-c) with six, five, and four remaining substitutable Br atoms, respectively, is reported. Octabromination results in facile chemical/electrochemical reduction, radical anion formation, and red-shifted optical properties. For the first time, diverse halogen-bonding interactions were identified in the PDA/PDI, which along with the attractive electronic features enhance the electron-transport characteristics compared to the di-/tetra-brominated PDIs (3/4).