Ori Green

• Doctor of Philosophy
• Principal Investigator at Technion – Israel Institute of Technology

The ability to selectively edit organic molecules at the atomic level has the potential to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. While numerous atom insertion and deletion reactions have recently been reported, examples of single atom swaps remain scarce due to the challenge of orchestrating the...

Singlet oxygen is a reactive oxygen species that causes oxidative damage to plant cells, but intriguingly it can also act as a signalling molecule to reprogram gene expression required to induce plant physiological/cellular responses. Singlet oxygen photosensitization in plants mainly occurs in chloroplasts after the molecular collision of ground-s...

The development of divergent methods to expedite structure–activity relationship studies is crucial to streamline discovery processes. We developed a rare example of regiodivergent ring expansion to access two regioisomers from a common starting material. To enable this regiodivergence, we identified two distinct reaction conditions for transformin...

Herein, a method for the isomerization of ketones in a manner akin to the chain-walking reaction of alkenes is described. Widely available and inexpensive pyrrolidine and elemental sulfur are deployed as catalysts to achieve this reversible transformation. Key to the utility of this approach was the elucidation of a stereochemical model to determin...

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The reaction uses a combination of commercially available phenyliodine(iii) diacetate (PIDA) and ammonium carbamate as the nitrogen source to furnish a wide range of isoquinolines. Various substitution patterns and commonly used functional groups are...

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The reaction uses a combination of commercially available (diacetoxy¬iodo)benzene (PIDA) and ammonium carbamate to furnish a wide range of isoquinolines. Various substitution patterns and commonly used functional groups are well tolerated and the ope...

Compared with peripheral late-stage transformations mainly focusing on carbon–hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite the recent flurry of activity in this area. Herein, we report the skeletal editing of indoles through nitrogen atom insertion,...

Advances in the field of late-stage functionalization have expedited lead-structure discovery and established new opportunities to access valuable molecules. Although many peripheral late-stage transformations, mainly focusing on C–H functionalizations, have been reported, reliable strategies to directly edit the core skeleton of lead compounds hav...

Carbon dioxide (CO2) impacts every aspect of life, and numerous sensing technologies have been established to detect and monitor this ubiquitous molecule. However, its selective sensing at the molecular level remains an unmet challenge, despite the tremendous potential of such an approach for understanding this molecule's role in complex environmen...

The sensitive detection of bacterial infections is a prerequisite for their successful treatment. The use of a chemiluminescent readout was so far hampered by an insufficient probe enrichment at the pathogens. We coupled siderophore moieties, that harness the unique iron transport system of bacteria, with enzyme‐activatable dioxetanes and obtained...

Adamantyl‐dioxetane luminophores are an important class of chemiluminescent molecular probes for diagnostics and imaging. We have developed a new efficient synthetic route for preparation of adamantyl‐enolether as precursors for dioxetane chemiluminescent luminophores. The synthesis is convergent, using an unusual Stille cross‐coupling reaction emp...

Adamantyl‐dioxetane luminophores are an important class of chemiluminescent molecular probes for diagnostics and imaging. We have developed a new efficient synthetic route for preparation of adamantyl‐enolether as precursors for dioxetane chemiluminescent luminophores. The synthesis is convergent, using an unusual Stille cross‐coupling reaction emp...

Der empfindliche Nachweis von bakteriellen Infektionen ist eine Voraussetzung für deren erfolgreiche Behandlung. Die Verwendung von chemilumineszenten Sonden wurde bisher durch deren unzureichende Anreicherung in den Erregern erschwert. Wir koppelten Siderophoreinheiten, welche über das bakterielle Eisentransportsystem in Pathogenen angereichert we...

In a myocardial infarction, blood supply to the left ventricle is abrogated due to blockage of one of the coronary arteries, leading to ischemia, which further triggers the generation of reactive oxygen species (ROS). These sequential processes eventually lead to the death of contractile cells and affect the integrity of blood vessels, resulting in...

We report a chemiluminescent probe (CLPT1) that permits the paired detection of tyrosinase (Tyr) and biological thiols. Tyr only leads to a poor chemiluminescence response, a finding ascribed to the formation of a stable o-benzoquinone intermediate. The addition of glutathione (GSH), or ascorbate to the o-benzoquinone intermediate results in thiol...

Protease chemiluminescent probes exhibit extremely high detection sensitivity for monitoring activity of various proteolytic enzymes. However, their synthesis, performed in solution, involves multiple synthetic and purification steps, thereby generating a major limitation for rapid preparation of such probes with diverse substrate scope. To overcom...

β-Lactamase positive bacteria represent a growing threat to human health because of their resistance to commonly used antibiotics. Therefore, development of new diagnostic methods for identification of β-lactamase positive bacteria is of high importance for monitoring the spread of antibiotic-resistant bacteria. Here, we report the discovery of a n...

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, be cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differ...

Natural killer (NK) cells are immune cells that can kill certain types of cancer cells. Adoptive transfer of NK cells represents a promising immunotherapy for malignant tumours; however, there is a lack of methods to validate anti‐tumour activity of NK cells in vivo. Herein, we report a new chemiluminescent probe to image in situ the granzyme B‐med...

In vivo detection of natural killer (NK) cell activity against tumours was achieved with an activatable chemiluminescent probe containing a granzyme B‐reactive peptide substrate linked to a phenoxydioxetane scaffold through a p‐aminobenzyl alcohol linker. The rapid and specific chemiluminescence response of the probe was used to detect NK cell acti...

The prostate specific antigen (PSA), a serine protease with chymotrypsin-like activity, is predominantly expressed in the prostate and is considered as the most common marker in use to identify and follow the progress of prostate cancer. In addition, it is also now accepted as a marker for detecting semen in criminal cases. Here, we describe the de...

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to different...

Selective and sensitive molecular probes for hydrogen peroxide (H2O2), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H2O2. A lack of reliable tools for in vivo imaging has hampered the development of H2O2 mediated therapeutics. By combining a speci...

Peroxide triggered, peroxide excited: Real‐time monitoring of hydrogen peroxide (H2O2) in rat brains has been achieved by combining a unique H2O2 sensing strategy and a peroxide bond excited chemiluminescent scaffold. This direct activation of phenoxy‐dioxetane by a tandem Payne/Dakin reaction provides a highly selective, sensitive, and rapid detec...

Detection of Salmonella and L. monocytogenes in food samples by current diagnostic methods requires relatively long time to results (2–6 days). Furthermore, the ability to perform environmental monitoring at the factory site for these pathogens is limited due to the need for laboratory facilities. Herein, we report new chemiluminescence probes for...

Detection of Salmonella and L. monocytogenes in food samples by current diagnostic methods requires relatively long time to results (2–6 days). Furthermore, the ability to perform environmental monitoring at the factory site for these pathogens is limited due to the need for laboratory facilities. Herein, we report new chemiluminescence probes for...

Activatable (turn‐on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer‐associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase‐1 (NQO1)‐specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporate...

Personalized hydrogels for engineering patient‐specific tissues are reported by Tal Dvir and co‐workers in article number 1803895. A small fatty tissue biopsy is taken from the patient by a minimally invasive procedure and the cellular and the a‐cellular materials then separated. While the cells are reprogrammed to become induced pluripotent stem c...

Activatable (turn‐on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer‐associated biomarkers can help drive advances in cancer research. Here we report a smart novel NAD(P)H:quinone oxidoreductase‐1 (NQO1) specific chemiluminescent Probe 1 that allows the differentiation between cancer subtypes. Probe 1 inco...

The utility of dioxetane-based chemiluminescent probes in biosensing and bioimaging is being increasingly recognized. While phenoxy-dioxetane luminophores with fast chemiexcitation kinetics are highly desired, current luminophores suffer from slow chemiexcitation. Herein we describe a rational, computationally-supported design of phenoxy-dioxetanes...

Despite incremental improvements in the field of tissue engineering, no technology is currently available for producing completely autologous implants where both the cells and the scaffolding material are generated from the patient, and thus do not provoke an immune response that may lead to implant rejection. Here, a new approach is introduced to...

Steady-state and time-resolved fluorescence techniques were employed to study a superphotoacid with a pKa* of ~-7, the chloro benzoate phenol cyanine picolinium salt (CBCyP) in acetonitrile-water mixtures. We found that the time-resolved fluorescence is bimodal. The amplitude of the short-time component depends on χwater; the larger χwater, the gre...

Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient...

Supplementary methods and figures.

Formaldehyde (FA) is a common environmental toxin that is also produced naturally in the body through a wide range of metabolic and epigenetic processes, motivating the development of new technologies to monitor this reactive carbonyl species (RCS) in living systems. Here, we report a pair of first‐generation chemiluminescent probes for selective f...

Steady-state and time-resolved fluorescence techniques as well as quantum-mechanical calculations were used to study the photophysics and photochemistry of a newly synthesized photoacid—the phenol cyanine picolinium salt. We found that the nonradiative rate constant knr of the excited protonated form of the photoacid is larger than that of the exci...

The majority of known chemiluminescent compounds produce light through oxidation-dependent mechanisms. The unique notion of triggering chemiluminescence by a chemical reaction other than oxidation was first introduced by Schaap in...

Formaldehyde (FA) is a common environmental toxin that is also produced naturally in the body through a wide range of metabolic and epigenetic processes, motivating the development of new technologies to monitor this reactive carbonyl species (RCS) in living systems. Here, we report a pair of first‐generation chemiluminescent probes for selective f...

Steady-state and time-resolved fluorescence techniques were employed to study the excited-state proton transfer (ESPT) rate to methanol, ethanol and propanol of a new photoacid, the chloro benzoate phenol cyanine picolinium salt (CBCyP). We found that the ESPT rate constants for methanol, ethanol and propanol are about 3 × 10¹² s⁻¹, 2 × 10¹² s⁻¹ an...

Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease....

Steady-state and time-resolved fluorescence techniques were employed to study the photoacidity of a newly synthesized photoacid, the chloro benzoate cyanine picolinium salt. It was found that the ESPT rate constant is ultrafast in water (kPT = 6.2 × 10¹²s⁻¹). We also found that the kinetic isotope effect is ∼1.7. The deprotonated form of the photoa...

Chemiluminescence luminophores are considered as one of the most sensitive family of probes for detection and imaging applications. Due to their high signal-to-noise ratio, luminophores with near-infrared (NIR) emission are particularly important for in vivo use. In addition, light with such long-wavelength has significantly greater penetration cap...

Singlet oxygen is among the ROS with the shortest life-time in aqueous media due to its extremely high reactivity. Therefore, designing sensors for detection of 1O2 is perhaps one the most challenging tasks in the field of molecular probes. Here we report a highly selective and sensitive chemiluminescence probe (SOCL-CPP) for detection of 1O2 in li...

Singlet oxygen is among the ROS with the shortest life-time in aqueous media due to its extremely high reactivity. Therefore, designing sensors for detection of 1O2 is perhaps one the most challenging tasks in the field of molecular probes. Here we report a highly selective and sensitive chemiluminescence probe (SOCL-CPP) for detection of 1O2 in li...

Steady-state and time-resolved fluorescence techniques were employed to study the excited-state proton transfer (ESPT) to water and D2O of a new photoacid, phenol benzoate cyanine picolinium salt (BCyP). We found that the ground-state pKa is about 6.5, whereas the excited-state pKa* is about -4.5. The ESPT rate constant, kPT, to water is ~0.5?10(12...

Chemiluminescence probes are considered to be among the most sensitive diagnostic tools that provide high signal-to-noise ratio for various applications such as DNA detection and immunoassays. We have developed a new molecular methodology to design and foresee light-emission properties of turn-ON chemiluminescence dioxetane probes suitable for use...

The nucleobase 5-hydroxymethylcytosine (5-hmC), a modified form of cytosine, is an important epigenetic mark related to regulation of gene expression. 5-hmC levels are highly dynamic during early development and are modulated during the progression of neurodegenerative disease and cancer. We describe a spectroscopic method for the global quantifica...

Optical genome mapping in nanochannels is a powerful genetic analysis method, complementary to DNA sequencing. The method is based on detecting a pattern of fluorescent labels attached along individual DNA molecules. When such molecules are extended in nanochannels, the labels create a fluorescent genetic barcode that is used for mapping the DNA mo...

Steady-state and time resolved fluorescence techniques and theoretical calculations, were employed to study the photoprotolytic properties of a newly synthesized photoacid 3-hydroxy-pyridine-dipicolinium cyanine (HPPC) dye. This dye is similar to Quinone cyanine 9, which we have previously studied and is the strongest photoacid currently synthesize...

The developments made in the last 12 years or so in the synthesis and application of self-immolative molecules that are based on dendritic, oligomeric, and polymeric structures are reviewed. Two basic disassembly reaction mechanisms are generally employed as tools to construct responsive self-immolative functions, quinone methide eliminations and c...