Ivan J. Dmochowski
· Alan MacDiarmid Term Professor of ChemistryVerifiedUniversity of Pennsylvania · Chemistry
Active 1996–2026
About
Ivan J. Dmochowski is the Alan MacDiarmid Term Professor of Chemistry at the University of Pennsylvania. His research focuses on a broad range of areas including Biological, Biophysical Chemistry, Chemical Biology, Chemical Physics and Physical Chemistry, Inorganic, and Materials Chemistry. He is based in room 348 N with laboratory spaces in rooms 332, 334, 336, and 338 N. The information provided highlights his interdisciplinary approach, integrating multiple chemistry subfields to advance understanding and innovation in these areas.
Research topics
- Chemistry
- Nuclear magnetic resonance
- Combinatorial chemistry
- Physical chemistry
- Physics
- Materials science
- Biochemistry
- Crystallography
- Biology
- Genetics
- Organic chemistry
- Stereochemistry
- Nanotechnology
Selected publications
Cavity acidification limits ferritin iron biomineralization
Journal of Inorganic Biochemistry · 2026-01-22
articleOpen accessSenior authorCorrespondingUnusually air-stable copper(<scp>i</scp>) complexes showing high selectivity for carbon monoxide
Chemical Science · 2025-01-01 · 1 citations
articleOpen accessSenior authorCorresponding. Spectroscopy, electrochemical, and X-ray crystal structure analyses indicate that the phenyl rotators of the capsule select for small axial ligands.
siRNA-Mimetic Ratiometric pH (sMiRpH) Probes for Improving Cell Delivery and mRNA Knockdown
ACS Chemical Biology · 2025-02-05 · 1 citations
articleSenior authorCorrespondingSecond-generation siRNA-mimetic ratiometric pH probes (sMiRpH-2) were developed by hybridizing a 3'-FAM-labeled 2'-OMe RNA strand with a 3'-Cy5-labeled 25mer RNA strand. These duplexes demonstrated the silencing of cytoplasmic mRNA targets in HeLa cells as measured by RT-qPCR and supported by western blot analysis. Fluorescence intensity and lifetime measurements revealed that a single guanosine (G) positioned adjacent to FAM achieves substantial static quenching at pH 5, with additional collisional quenching rendering the dye almost nonemissive. A FAM-G π-π stacking interaction was evidenced by a red-shifted absorbance spectrum for FAM. Decreased quenching at near-neutral pH enhances the FAM dynamic range in the physiologic pH window and improves the differentiation in cells between endocytic entrapment and cytoplasmic release. Flow cytometric analysis of intracellular pH and uptake using sMiRpH-2 was corroborated by live cell confocal microscopy and found to be predictive of knockdown efficacy. A sMiRpH-2 probe successfully predicted the relative efficacy of two transfection agents in more challenging SK-OV-3 cells, which highlights its use for the rapid assessment of nonviral siRNA delivery vectors.
Journal of Materials Chemistry B · 2025-01-01 · 1 citations
erratumOpen accessSenior authorCorrespondingCorrection for ‘Charge engineering controls cooperative assembly and loading in protein host–guest complexes’ by Zhiheng Wang et al. , J. Mater. Chem. B , 2025, https://doi.org/10.1039/D5TB01202C.
Exosome-Mediated Mitochondrial Delivery of Antisense Oligonucleotides
Nucleic Acid Therapeutics · 2025-06-25
articleOpen accessSenior author-methyl (2'-OMe) RNA oligonucleotides (oligos) to mitochondria for antisense applications, with potential for implementation in other mitochondrial DNA (mtDNA)-targeted therapies. Exosomes, which are nanoscale, naturally occurring extracellular vesicles (EVs), have been employed for biotechnology applications in oligonucleotide delivery in recent years. We discovered that exosomes from fetal bovine serum (FBS) can be used as a simple and biologically compatible delivery agent of 2'-OMe RNA antisense oligonucleotides to cellular mitochondria, leading to target protein knockdown. While most RNA interference and antisense mechanisms occur in the cytoplasm or nucleus, the need for mitochondrial targeting has become increasingly apparent. Mitochondrial disease describes a variety of currently incurable syndromes that especially affect organs requiring significant energy including the muscles, heart, and brain. Many of these syndromes result from mutations in mtDNA, which codes for the 13 proteins of the oxidative phosphorylation system and are thus often implicated in inherited metabolic disorders.
Soft Matter · 2025-01-01
erratumOpen accessCorrection for ‘Interfacial rheology of lanthanide binding peptide surfactants at the air–water interface’ by Stephen A. Crane et al. , Soft Matter , 2024, 20 , 9161–9173, https://doi.org/10.1039/D4SM00493K.
RIBOsensor for FRET-based, real-time ribose measurements in live cells
Chemical Science · 2025-01-01 · 2 citations
articleOpen accessSenior authorCorrespondingd-Ribose is a building block of many essential biomolecules, including all nucleic acids, and its supplementation can enhance energy production, particularly under stress conditions such as ischemia and heart failure. The distribution, biosynthesis, and regulation of ribose in mammalian systems remain poorly understood. To explore intracellular ribose dynamics, we developed a genetically encoded fluorescence resonance energy transfer (FRET) sensor using ribose binding protein (RBP) and enhanced cyan and yellow fluorescent proteins (FPs). The RIBOsensor, which positions one FP near the active site of RBP, achieves the necessary sensitivity for cellular imaging by increasing the FRET signal upon ribose binding, compared to traditional N- and C-terminal FP orientations. This sensor rapidly, reversibly, and selectively detects labile ribose in live cells-enabling longitudinal studies-and can be employed for intracellular ribose quantitation, which provides a valuable tool for investigating ribose transport and metabolism in normal and disease states.
Charge engineering controls cooperative assembly and loading in protein host–guest complexes
Journal of Materials Chemistry B · 2025-01-01 · 1 citations
articleOpen accessSenior authorferritin. Guided by molecular dynamics (MD) simulations and computational protein design, experiments confirmed that GFP charge magnitude and distribution dictate capsule assembly and loading efficiency. These data provide the first example of cooperative assembly with a ferritin capsule. Finally, we established a strategy for generating stoichiometric 1 : 1 protein host-guest complexes, confirmed by time-resolved fluorescence anisotropy. This provides a blueprint for designing ferritin host-guest complexes with enhanced homogeneity and functionality.
Analytical Chemistry · 2025-02-04
articleOpen accessIn 2022, the FDA approved hyperpolarized (HP) 129Xe gas as an inhalable contrast agent for functional lung imaging. For clinical imaging, HP 129Xe is usually given as a bolus inhalation. However, for preclinical applications (e.g., pulmonary imaging in small rodents), the continuous delivery of HP 129Xe is greatly desired to enable MRI scanning under conditions of physiological continuous animal breathing patterns. Moreover, HP 129Xe gas can be utilized for other applications including materials science and bioanalytical chemistry, where a continuous flow of hyperpolarized gas through an NMR sample over several minutes is also desired for sensing of 129Xe inside an NMR spectrometer. 129Xe is often hyperpolarized using continuous-flow spin-exchange optical pumping, which employs a lean (1–2%) mixture of Xe and a carrier gas (e.g., He and N2). The low Xe concentration in the produced output reduces the NMR detection sensitivity, and thus, Xe cryo-collection is typically employed to achieve near-100% pure gas-phase Xe before administration to the sample or subject. However, the need for cryo-collection undermines a key advantage of continuous-flow production, i.e., the continuous flowing in a hyperpolarizer HP 129Xe gas is trapped inside the hyperpolarizer, and the produced HP 129Xe gas is released at once when the production cycle (30–60 min) is completed. An alternative HP 129Xe production technology employs a “stopped-flow” approach, where a batch of HP gas is hyperpolarized over time and quickly released from a hyperpolarizer. Here, a clinical-scale “stopped-flow” 129Xe hyperpolarizer was employed to hyperpolarize a 1.3 L-atm batch of 50:50 Xe:N2 gas mixture inside a glass cell with an ultralong lifetime of the HP 129Xe state (T1 > 2 h). The produced HP 129Xe gas was slowly delivered into a 5 mm NMR tube via PEEK tubing under a wide range of gas flow rates: 3–180 standard cubic centimeters per minute (sccm). The polarization of the gas ejected from the hyperpolarizer was quantified using in situ low-field NMR polarimetry and additionally verified using a 0.35 T clinical MRI scanner. Continuous-flow delivery of HP 129Xe was demonstrated for up to 15 min with a gas flow rate of 45–150 sccm over a 2.5-m length of PEEK tubing, suffering only small losses in 129Xe polarization. These observations are additionally supported by 129Xe relaxation measurements inside the PEEK tubing employed for gas delivery and the 5 mm NMR tube employed for polarimetry. 129Xe polarization of 16–19% was obtained in the delivered gas, starting with an “in-polarizer” 129Xe polarization of 19%. We envision that this method can be employed for on-demand cryogen-free delivery of hyperpolarized gas using “stopped-flow” 129Xe hyperpolarizers for a broad range of applications, from preclinical imaging to biosensors, and to spectroscopy of materials surfaces.
Improved Large-Scale Synthesis of Acridonylalanine for Diverse Peptide and Protein Applications
Bioconjugate Chemistry · 2024-11-12 · 4 citations
articleOpen accessFluorescent unnatural amino acids give biochemists, biophysicists, and bioengineers new ways to probe the properties of proteins and peptides. Here, the synthesis of acridon-2-ylalanine (Acd) is optimized for large-scale production to enable ribosomal incorporation through genetic code expansion (GCE), and fluorenylmethoxycarbonyl (Fmoc)-protected Acd is prepared for solid-phase peptide synthesis (SPPS). We demonstrate the utility of Acd in several applications: first, Acd quenching by Tyr is used in the design of fluorescent protease sensors made by SPPS. Second, we demonstrate Acd incorporation into a lanthanide-binding peptide that is generated either by GCE or by SPPS and demonstrate the utility of Acd for sensitizing the emission of Eu3+. Finally, Acd is inserted into the intrinsically disordered protein, α-synuclein, using GCE and used to study ion binding and aggregation.
Recent grants
NIH · $308k · 2009
Computationally designed synergistic protein-nanoparticle assemblies
NSF · $545k · 2015–2018
MRI: Acquisition of Tri-Institutional, Cyber-Enabled Chemistry MALDI-TOF Mass Spectrometer
NSF · $435k · 2008–2011
NIH · $995k · 2008
Light-activated oligonucleotides for biological applications
NIH · $3.0M · 2008–2019
Frequent coauthors
- 51 shared
Serge D. Zemerov
University of Pennsylvania
- 30 shared
P. Aru Hill
Denison University
- 30 shared
Benjamin W. Roose
Merck & Co., Inc., Rahway, NJ, USA (United States)
- 26 shared
Teresa L. Rapp
University of Washington
- 25 shared
Jeffery G. Saven
University of Pennsylvania
- 24 shared
Michael R. Gau
- 23 shared
Yanfei Wang
- 21 shared
Katherine W. Pulsipher
University of Pennsylvania
Awards & honors
- Caltech Herbert Newby McCoy Award (2000)
- Helen Hay Whitney Postdoctoral Fellow, Biophysics, Caltech (…
- Camille and Henry Dreyfus New Faculty Award (2003)
- National Science Foundation CAREER Award (2005)
- Camille and Henry Dreyfus Teacher-Scholar Award (2007)
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