Bipyridine Moieties Research Articles

Four compounds containing 1-(2-carboxyethyl)-4,4′-bipyridine: Synthesis, crystal structure and chromic behavior

Herein, four compounds containing the neutral viologen derivative, 1-(2-carboxyethyl)-4,4′-bipyridine (CBbpy) have been synthesized, (CBbpy)·(H2TPDC)·H2O (1), [Co0.5(CBbpy)(H2O)2](HTPDC)·2 H2O (2), [Ni0.5(CBbpy)(H2O)2](HTPDC)·2 H2O (3) and {[Cd(CBbpy)2(H2O)2][Cd(TPDC)2]·4 H2O}n (4) (H2TPDC = thiophene-2,5-dicarboxylic acid). Compound 1 is a co-crystal that forms the donor-acceptor (D-A) system through non-covalent interactions. Compounds 2 and 3 own the same isolated structure, in which metal ions coordinate with CBbpy to form cations, while H2TPDC loses a proton to form anions. Compound 4 contains one-dimensional (1D) {[Cd(CBbpy)2(H2O)2]2+}n double chain and two-dimensional (2D) {[Cd(TPDC)2]2-}n layer, which leads to a 1D + 2D→three-dimensional (3D) interdigitated supramolecular architecture. Although four compounds comprise the same bipyridinium moiety, their chromic behaviors are different. Compounds 1 and 4 own reversible photochromic action, while 2 and 3 reveal hydrochromic action upon heating. Based on the photochromic properties of 1 and 4, the photo-modulated fluorescence and the potential applications of inkless and erasable printing are investigated.

Crystal structure and stimulus-responsive properties of three functional compounds containing 1-carboxyethyl-4,4′-bipyridine

Herein, three compounds containing the neutral viologen derivative, 1-carboxyethyl-4,4′-bipyridine (CEbpy) have been synthesized, (CEbpy)·(H2TPDC)·2H2O (1) [Co(CEbpy)(TPDC)(H2O)4]·3H2O (2) and [Cd3(CEbpy)2(TPDC)3·7H2O]n (3) (H2TPDC = thiophene-2,5-dicarboxylic acid). Compound 1 is a supramolecular assembly, linked by non-covalent interactions to constitute the donor-acceptor (D-A) system. Compound 2 owns a zero-dimensional (0D) isolated structure in which metal ions are coordinated with CEbpy and fully deprotonated (TPDC)2- ligands. Compound 3 exhibits a three-dimensional (3D) framework of trinuclear metal clusters, where each metal atom forms its own distinct linear one-dimensional (1D) chain along a specific axis. Although the three compounds comprise the same bipyridinium moiety and aromatic acid, their chromic behaviors are different. Compounds 1 and 3 exhibit reversible photochromism, while 2 reveals hydrochromism upon heating. Additionally, photo-modulated fluorescence as well as their potential applications in inkless erasable printing have been studied.

Hollow porous organic framework nanotube for efficient photocatalytic H2O2 generation by promoting H2O oxidation

The hydrogen peroxide (H2O2) generation by photocatalytic O2 reduction coupling H2O oxidation is a promising alternative to the traditional anthraquinone method. However, the low mass transfer and weak water oxidation are still the major responsible for the low efficiency of photocatalytic H2O2 production. Herein, we present a porous organic framework (BPTEE-POF) with hollow nanotube structure containing 2,2′-bipyridine active center of H2O oxidation, which was synthesized by template-free Sonogashira cross-coupling reaction of 5,5′-dibromo-2,2′-bipyridine (BP) and 1,1,2,2-tetrakis(4-ethynylphenyl)ethene (TEE). The 2,2′-bipyridine moieties can effectively weaken HO bond and facilitate H2O oxidation to generate O2 and H+, which can be subsequently employed as reactants for non-sacrificial H2O2 production. Meanwhile, the throughout hollow structure of BPTEE-POF is conducive to mass transfer/diffusion of substrate and product by siphoning, which promotes O2 and H2O molecules to contact with catalytic active sites and causes the quick dissociation of H2O2 from active sites, thereby boosting the overall reaction kinetic and efficiency.

Exploring Raloxifene-Based Metallodrugs: A Versatile Vector Combined with Platinum(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) poses challenges in therapy due to the absence of target expression such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Frequently, the treatment of TNBC involves the combination of several therapeutics. However, an enhanced therapeutic effect can be also achieved within a single molecule. The efficacy of raloxifene can be improved by designing a raloxifene-based hybrid drug bearing a 2,2'-bipyridine moiety (2). Integration of platinum(II), palladium(II), and nickel(II) complexes into this structure dramatically changed the cytotoxicity. The platinum(II) dichloride complex 3 did not demonstrate any activity, while palladium(II) and nickel(II) dichloride complexes 4 and 5 exhibited various cytotoxic behavior towards different types of hormone-receptor positive (HR+) cancer and TNBC cell lines. The replacement of the two chlorido ligands in 3-5 with a dicarbollide (carborate) ion [C2B9H11]2- resulted in reduced activity of compounds 6, 7, and 8. However, the palladacarborane complex 7 demonstrated higher selectivity towards TNBC. Furthermore, the mechanism of action was shifted from cytotoxic to explicitly cytostatic with detectable proliferation arrest and accelerated aging, characterized by senescence-associated phenotype of TNBC cells. This study provides valuable insights into the development of hybrid therapeutics against TNBC.

A Cofacial Porphyrin Dimer Generated by Cooperative Zinc Ion Binding

Noncovalent cofacial porphyrin dimers have attracted interest due to their potential use as host materials or catalysts. In this study, we introduce a novel coordination‐directed cofacial porphyrin dimer from a meso‐tetraphenylporphyrin derivative modified with 2,2'bipyridine moieties at the meta positions of the phenyl groups. Spectroscopic investigation has shed light on the binding processes and the structure of the dimer in solution in detail. Initial Zn2+ ion binding to the porphyrin hinders the subsequent Zn2+ binding and the binding of the second porphyrin. However, once the dimer is formed, additional Zn2+ binding is notably enhanced, resulting in a pronounced S‐shaped binding curve. The detailed structure of the dimer in solution was established based on UV‐vis spectroscopy, various 1H NMR spectroscopy techniques and mass spectrometry. Simulations of ringcurrent‐induced chemical shift changes provided evidence for the face‐to‐face porphyrin structure with tetrahedral coordination of the bipyridine ligands. The X‐ray single crystal structure provided conclusive evidence for the structure of the face‐to‐face dimer, which remarkably resembles the model structure from the 1H NMR simulation. The stability of the dimer structure makes it promising for further exploration of this motif in developing new supramolecular structures and for their potential applications as host compounds and catalysts.

Bipyraloxifene - a modified raloxifene vector against triple-negative breast cancer.

Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2'-bipyridine (2,2'-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2'-bipyridin-4'-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.

Synthesis and Photocatalytic CO2 Reduction of a Cyclic Zinc(II) Porphyrin Trimer with an Encapsulated Rhenium(I) Bipyridine Tricarbonyl Complex.

We previously reported a cyclic Zn(II) porphyrin trimer in which three Zn porphyrins are alternately bridged by three 2,2'-bipyridine (bpy) moieties, enabling the encapsulation of metal complexes within the nanopore formed by the Zn porphyrins. In this study, we introduced a [Re(CO)3 Br] fragment into one of the bpy moieties of the cyclic trimer to form the catalytic Re(4,4'-R2 -bpy)(CO)3 Br center (R=methyl ester). The ester groups (R) play an important role in the synthesis of the cyclic structure. However, it was observed that these ester groups significantly deactivated the photocatalytic CO2 reduction reaction. Therefore, we converted the ester groups with a suitable reducing reagent into hydroxymethyl groups, followed by acetylation to form acetoxymethyl groups. This modification remarkably enhanced the photocatalytic activity of the cyclic trimer=Re complex system for CO2 reduction. Moreover, in the modified system, the presence of the Re complex induced room-temperature phosphorescence of the Zn porphyrin. The phosphorescence was significantly quenched by 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole, indicating that efficient electron transfer mediated by the excited triplet state of the Zn porphyrin occurs during the photocatalytic CO2 reduction.

The impact of carboxylic acid anchoring groups on the optoelectronic and nonlinear optical properties of Ru complex dyes: A computational approach

In this study, density functional theory (DFT) and time-dependent DFT (TD-DFT) methods were used to analyze the effects of varying the number and positions of carboxylic acid anchoring groups attached to the bpy ligand of the [Ru(bpy)2(NCS)2] complex. Also the geometric structures, absorption geometry, electronic structures, optical properties, photovoltaic parameters, and nonlinear optical (NLO) properties of the designed [Ru(bpy)2(NCS)2] derivatives were investigated and compared with each other. The results indicate that the optoelectronic properties of these ruthenium (II) complexes are influenced by the number and positioning of carboxylic acid groups on the bipyridine moiety. Calculated values of ΔGinject and ΔGreg for the studied Ru(II) complexes suggest that the energy level alignment with the semiconductor and electrolyte satisfies the criteria. Furthermore, it was observed that the number and position of the anchoring carboxylic acid units is an effective approach to improve their NLO response. Overall, the structural modifications by the anchoring carboxylic acid groups on the bpy ligand of [Ru(bpy)2(NCS)2] complexes seem to fine-tune their DSSC performance and NLO response characteristics.

Nitrogen-rich silk fibroin aerogel for effective removal of radioactive iodine

Removal of radioactive iodine compounds such as iodomethane and iodine using adsorption methods is a challenge due to the high cost and poor retention capacity of adsorption materials. Herein, a novel silk fibroin composite aerogel containing bipyridine and diethylamine (SBA) was prepared and evaluated for the removal of radioactive iodine. SBA can efficiently remove iodomethane and iodine with an adsorption capacity of 724.3 mg g−1, which is 5.5 times that of a pure silk fibroin aerogel (SFA) (132.5 mg g−1 for SFA), and 347.5 mg g−1 (121.7 mg g−1 for SFA), respectively. X-ray photoelectron and 13C nuclear magnetic resonance spectroscopies reveal that the good adsorption performance of SBA can be attributed to the interaction between the radioactive pollutants and the bipyridine and diethylamine moieties on the SBA backbone. Moreover, after ten adsorption cycles, SBA retains 91.7% of its initial adsorption capacity, demonstrating its potential for environmental remediation.

Two crystalline Zn(II)-viologen compounds with photochromism, photomodulated luminescence and water-induced reversible crystal-to-amorphous transformation

In this work, two Zn(II)-viologen compounds, {[Zn(cpbpy)(L)](H2O)5}n (1) and [Zn(H2O)6](cpbpy)2(L)2(H2O)2 (2) (cpbpy = N-(3-carboxypyridin-5-yl)− 4,4′-bipyridinium, H2L = 1,4-benzenedicarboxylic acid) have been constructed via different synthetic routes. Structural analysis exhibits compound 1 features a two-dimension layered structure consisting of one-dimension [Zn(L)]n chains and bridging cpbpy ligands while compound 2 exists as a discrete monomeric structure. In a very short period of time, both compounds display electron-transfer photochromic behaviors. However, the photoproduct of compound 2 is more stable than compound 1 in air, which is attributed to better coplanarity of pyridyl rings of 4,4′-bipyridine moieties in compound 2. Also, both compounds show photomodulated luminescence properties. Strikingly, compound 2 also exhibits interesting water-induced reversible crystal-to-amorphous transformation accompanying with reversible luminescence switch behavior. To our knowledge, this is the first example of a crystalline viologen-based compound that displays water-induced reversible crystal-to-amorphous transformation.

Self-Assembly of Triple-Stranded Lanthanide Molecular Quasi-Lantern Containing 2,2'-Bipyridine Receptor: Luminescence Sensing and Magnetic Property.

Ln2L3-type supramolecular architectures have received significant attention recently due to their unique magnetism and optical properties. Herein, we report the triple-stranded Ln2L3-type lanthanide molecular quasi-lanterns, which are fabricated by the deprotonation self-assembly of a linear ligand featuring a β-diketone chelating claw and 2,2'-bipyridine (bpy) moiety with lanthanide ions (Ln = Eu3+ and Dy3+). The crystal structure analysis indicates that Eu3+ and Dy3+ ions are all coordinated by eight oxygen donors but in different coordination geometries. The eight oxygen donors in Eu2L3 and Dy2L3 are arranged in a square antiprism and triangular dodecahedron geometry, respectively. Taking into account the fact that the bpy moiety has a strong coordination affinity for transition metal ions, luminescence sensing toward Cu2+ ions has been demonstrated with Eu2L3, bearing a detection of limit as low as 2.84 ppb. The luminescence sensing behavior of Eu2L3 is ascribed to the formation host-guest complex between Eu2L3 and Cu2+ ions with a 1:2 binding ratio. Dynamic AC susceptibility measurements for Dy2L3 reveal the relaxation of magnetization in it. This work provides a potential way for design and fabrication of lanthanide-based molecular materials with functions endowed by the ligands.

Stimuli-Responsive Self-Healing Luminescent Materials Based on Lanthanide Ions and Bipyridine Moieties

Contemporary, luminescent materials possessing rapid stimulus-responsive characteristics demonstrate considerable potential in anti-counterfeiting applications. However, if anti-counterfeiting materials become damaged during use, the integrity of the information will be compromised. Consequently, endowing materials with self-healing ability can ensure the accuracy and integrity of anti-counterfeiting data. In this study, a luminescent metallo-supramolecular polymer is synthesized through the coordination of lanthanide ions (Ln3+) and bipyridine ligands within polyurethane (PU) chains. The PU elastomers created using 4,4′-dicyclohexylmethane diisocyanate display remarkable transmittance and hydrophobic properties following coordination with Ln3+. The dynamic Ln–N coordination imparts self-healing behavior and robust mechanical performance to the PU elastomers. The “antenna effect” imbues the resulting materials with exemplary luminescent properties, and the emission color can be conveniently modulated by adjusting the Eu3+/Tb3+ ratio. Importantly, all luminescent materials exhibit a rapid stimulus-response to acid-base fluctuations through the disruption or restoration of the “antenna effect” between Ln3+ and bipyridine, a critical aspect for the advancement of materials in the anti-counterfeiting and information encryption domains.

Synthesis and Reactivity of an Anti-van't Hoff/Le Bel Compound with a Planar Tetracoordinate Silicon(II) Atom.

For a long time, planar tetracoordinate carbon (ptC) represented an exotic coordination mode in organic and organometallic chemistry, but it is now a useful synthetic building block. In contrast, realization of planar tetracoordinate silicon (ptSi), a heavier analogue of ptC, is still challenging. Herein we report the successful synthesis and unusual reactivity of the first ptSi species of divalent silicon present in 3, supported by the chelating bis(N-heterocyclic silylene)bipyridine ligand, 2,2'-{[(4-tBuPh)C(NtBu)]2SiNMe}2(C5N)2, 1]. The compound resulted from direct reaction of 1 with Idipp-SiI2 [Idipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Alternatively, it can also be synthesized by a two-electron reduction of the corresponding Si(IV) precursor 2 with 2 molar equiv of KC10H8. Density functional theory calculations show that the lone pair at the ptSi(II) resides almost completely in its 3pz orbital, very different from known four-coordinate silylenes. Oxidative addition of MeI to the ptSi(II) atom affords the corresponding pentacoordinate Si(IV) compound 4, with the methyl group located in an apical position. Remarkably, the reaction of 2 with [CuOtBu] leads to the regeneration of the bis(silylene) arms via Si-Si bond scission and induces the Si(II) → Si(IV) oxidation of the central Si(II) atom and concomitant two-electron reduction of the bipyridine moiety to form the neutral bis(silylene)silyl Cu(I) complex 5.

Viologens and extended viologen derivatives with mono- and di-hexyl substituents for highly stable all-in-one ECDs and solar cell powered large-area ECDs

Viologen-based electrochromic devices (ECDs) have attracted considerable attention due to their potential applications in smart windows. Herein, two viologen derivatives with N-substituted monohexyl (MHEV) and dihexyl (DHEV), and two extended viologen derivatives with a thiophene unit inserted between the bipyridine moieties and N-substituted monohexyl (m-MHEV) and dihexyl (m-DHEV) were synthesized. All-in-one ECDs were assembled using these materials. m-DHEV and m-MHEV-based ECDs exhibited red and dark orange colors, while DHEV and MHEV-based ECDs exhibited blue and magenta colors. The extended conjugation of the chromophore by the thiophene unit endowed the devices with visible-NIR absorption and excellent cyclic stability. After 10000 cycles, ECDs based on m-DHEV and m-MHEV retained 94.2% and 95.0% of their initial optical contrasts, respectively. A binary chromophore mixture of DHEV and m-DHEV was used to fabricate a uniform large-area ECD (8 cm × 8 cm) with strong sunlight absorption ability. The device maintained high optical contrast (80.2% of initial state) after 2000 cycles. Furthermore, a solar cell powered ECD (8 cm × 8 cm) with negligible loss of optical contrast after 100 cycles of coloring and bleaching under sunlight was developed, demonstrating the application potential of self-powered smart windows using these materials.

Heteropolymetallic [FeFe]-Hydrogenase Mimics: Synthesis and Electrochemical Properties.

The synthesis and electrochemical properties of tetranuclear [Fe2S2]-hydrogenase mimic species containing Pt(II), Ni(II), and Ru(II) complexes have been studied. To this end, a new tetranuclear [Fe2S2] complex containing a 5,5'-diisocyanide-2,2'-bipyridine bridging ligand has been designed and coordinated to the metal complexes through the bipyridine moiety. Thus, the tetranuclear [Fe2S2] complex (6) coordinates to Pt(II), Ni(II) and Ru(II) yielding the corresponding metal complexes. The new metal center in the bipyridine linker modulates the electronic communication between the redox-active [Fe2S2] units. Thus, electrochemical studies and DFT calculations have shown that the presence of metal complexes in the structure strongly affect the electronic communication between the [Fe2S2] centers. In the case of diphosphine platinum compounds 10, the structure of the phosphine ligand plays a crucial role to facilitate or to hinder the electronic communication between [Fe2S2] moieties. Compound 10a, bearing a dppe ligand, shows weak electronic communication (ΔE = 170 mV), whereas the interaction is much weaker in the Pt-dppp derivative 10b (ΔE = 80 mV) and virtually negligible in the Pt-dppf complex 10c. The electronic communication is facilitated by incorporation of a Ru-bis(bipyridine) complex, as observed in the BF4 salt 12 (ΔE = 210 mV) although the reduction of the [FeFe] centers occurs at more negative potentials. Overall, the experimental-computational procedure used in this work allows us to study the electronic interaction between the redox-active centers, which, in turn, can be modulated by a transition metal.

Enhanced Energy Transfer in A π‐Conjugated Covalent Organic Framework Facilitates Excited‐State Nickel Catalysis

AbstractCovalent organic frameworks (COFs) have received broad interest owing to their permanent porosity, high stability, and tunable functionalities. COFs with long‐range π‐conjugation and photosensitizing building blocks have been explored for sustainable photocatalysis. Herein, we report the first example of COF‐based energy transfer Ni catalysis. A pyrene‐based COF with sp2 carbon‐conjugation was synthesized and used to coordinate NiII centers through bipyridine moieties. Under light irradiation, enhanced energy transfer in the COF facilitated the excitation of Ni centers to catalyze borylation and trifluoromethylation reactions of aryl halides. The COF showed two orders of magnitude higher efficiency in these reactions than its homogeneous control and could be recovered and reused without significant loss of catalytic activity.

Enhanced Energy Transfer in A π-Conjugated Covalent Organic Framework Facilitates Excited-State Nickel Catalysis.

Covalent organic frameworks (COFs) have received broad interest owing to their permanent porosity, high stability, and tunable functionalities. COFs with long-range π-conjugation and photosensitizing building blocks have been explored for sustainable photocatalysis. Herein, we report the first example of COF-based energy transfer Ni catalysis. A pyrene-based COF with sp2 carbon-conjugation was synthesized and used to coordinate NiII centers through bipyridine moieties. Under light irradiation, enhanced energy transfer in the COF facilitated the excitation of Ni centers to catalyze borylation and trifluoromethylation reactions of aryl halides. The COF showed two orders of magnitude higher efficiency in these reactions than its homogeneous control and could be recovered and reused without significant loss of catalytic activity.

Synthesis, structures, and solid-state photoresponsive color change behavior of boronium complexes bearing a pyridine-imine, diimine, or pyridine-ketone bidentate ligand.

9-Borabicyclo[3.3.1]nonane-based boronium triflates bearing a N-substituted 2-pyridylmethanimine, N,N'-dialkylethane-1,2-diimine, or 2-arylcarbonylpyridine ligand were synthesized. Their tetracoordinate boron structures were determined using 11B NMR spectra and X-ray crystallography. The pyridine-imine complexes exhibited solid-state photoresponsive color changes upon UV irradiation, which indicated that boronium complexes without a bipyridine moiety also have photoresponsive capabilities. Combination of TD-DFT calculations and measurements of UV-vis absorption and fluorescence properties, diffuse reflectance spectra, and ESR spectra provided suggestions on the determining factor of the photoresponsive color change capabilities and structures of the photoproducts.

A π-conjugated covalent organic framework enables interlocked nickel/photoredox catalysis for light-harvesting cross-coupling reactions.

Covalent organic frameworks (COFs) are an outstanding platform for heterogeneous photocatalysis. Herein, we synthesized a pyrene-based two-dimensional C[double bond, length as m-dash]C linked π-conjugated COF via Knoevenagel condensation and anchored Ni(ii)-centers through bipyridine moieties. Instead of traditional dual metallaphotoredox catalysis, the mono-metal decorated Ni@Bpy-sp2c-COF interlocked the catalysis mediated by light and the transition metal. Under light irradiation, enhanced energy and electron transfer in the COF backbone, as delineated by the photoluminescence, electrochemical, and control experiments, expedited the excitation of Ni centers to efficiently catalyze diverse photocatalytic C-X (X = B, C, N, O, P, S) cross-coupling reactions with efficiencies orders of magnitude higher than the homogeneous controls. The COF catalyst tolerated a diverse range of coupling partners with various steric and electronic properties, delivering the products with up to 99% yields. Some reactions were performed on a gram scale and were applied to diversify pharmaceuticals and complex molecules to demonstrate the synthetic utility.

2-Phenoxy-3, 4′-bipyridine derivatives inhibit AURKB-dependent mitotic processes by disrupting its localization

Activity-based drug screens have successfully led to the development of various inhibitors of the catalytic activity of aurora kinases (AURKs), major regulatory kinases of cell division. Disrupting the localization of AURKB, rather than its catalytic activity, represents a largely unexplored alternative approach to disabling AURKB-dependent processes. Localization disruptors could be just as specific as direct inhibitors of AURKB activity, may bypass their off-target and select on-target toxicities, and are likely less susceptible to drug resistance resulting from mutations of the AURKB catalytic site. In this study, we demonstrate that the pan-AURK inhibitor AMG900 works at a low concentration not by inhibiting the phosphorylation of H3 at Ser10, an AURKB substrate, but by disrupting the mitotic localization of AURKB. Structural deletion studies pinpoint this undescribed activity to the 2-phenoxy-3,4′-bipyridine moiety of AMG900. Guided by a mechanism-informed phenotypic screening (MIPS) assay, the drug fragment is optimized into a novel class of inhibitors that, at low nanomolar concentrations, can disable AURKB through disruption of its mitotic localization and have desirable oral PK properties. Hierarchical clustering of cell fitness profiles reveals that these compounds cluster with each other, rather than with known AURK inhibitors such as AMG900 and VX-680. Validation studies in mice demonstrate that compound 15a elicits mitotic arrest and apoptosis in NCI–H23 human lung adenocarcinoma xenografts, resulting in a pronounced suppression of tumor growth. The discovery and optimization of compounds that disrupt AURKB localization are successfully facilitated by MIPS. Our findings suggest that 2-phenoxy-3, 4′-bipyridine derivatives have the potential to be further developed as effective therapeutics for the treatment of malignancy by delocalizing AURKB.