Kevin D Belfield

• Ph.D.
• Head of Faculty at New Jersey Institute of Technology

Neutral rhodol-based red emitters are shown to efficiently localize in mitochondria, as demonstrated by confocal microscopy and co-localization studies.

The widespread use and impervious nature of per- and polyfluorinated alkyl substances (PFASs) is leading to potentially harmful exposure in numerous environments. One avenue to explore remediation of PFAS-contaminated environments involves investigating how well PFASs adsorb onto various substrates. In the current review, we focus on summarizing re...

Coumarin-based fluorescent agents play an important role in the manifold fundamental scientific and technological areas and need to be carefully studied. In this research, linear photophysics, photochemistry, fast vibronic relaxations, and two-photon absorption (2PA) of the coumarin derivatives, methyl 4-[2-(7-methoxy-2-oxo-chromen-3-yl)thiazol-4-y...

Hemorrhage is a major component of traumatic brain injury (TBI). Red blood cells, accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion and release free iron into the central nervous system. This iron must be managed to prevent iron neurotoxicity and ferroptosis. As prior alcohol consumption is often associated with TBI, we e...

Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition,...

The development of contrast agents based on fluorescent nanoparticles with high brightness and stability is a key factor to improve the resolution and signal-to-noise ratio of current fluorescence imaging techniques. However, the design of bright fluorescent nanoparticles remains challenging due to fluorescence self-quenching at high concentrations...

The nature of linear photophysical and nonlinear optical properties of a new squaraine derivative 2,4-bis[4-(azetidyl)-2-hydroxyphenyl]squaraine (1) with efficient near-infrared (NIR) emission was comprehensively analyzed based on spectroscopic, photochemical, and two-photon absorption (2PA) measurements, along with quantum chemical analysis. The s...

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca ²⁺ ] e ), but the local [Ca ²⁺ ] e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca ²⁺ ] e in the mouse calvarial bone mar...

Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs) accumulated at the hemorrhagic site undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) that must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis that c...

Hemorrhage is a major component of traumatic brain injury (TBI). Red blood cells, accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion and release free iron into the central nervous system. This iron must be managed to prevent iron neurotoxicity and ferroptosis. As prior alcohol consumption is often associated with TBI, we e...

Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs), accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) which must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis tha...

We have shown that the effects of low-dose ethanol promote the clearance of waste metabolites, such as amyloid-beta (Aβ) proteins, from the brain through the perivascular space (PVS). We demonstrated that dilative reactivity of arterial smooth muscle and endothelial cells regulate this clearance. These findings indicate the importance of blood-brai...

The electronic nature of 4-hydroxy-1H-pyrrolo[3,4-c]pyridine-1,3,6(2H,5H)-trione (HPPT) was comprehensively investigated in liquid media at room temperature using steady-state and time-resolved femtosecond transient absorption spectroscopic techniques. The analysis of the linear photophysical and photochemical parameters of HPPT, including steady-s...

A fluorescently labeled peptide that exhibited fast excited state intramolecular proton transfer (ESIPT) was synthesized, and the nature of its electronic properties was comprehensively investigated, including linear photophysical and photochemical characterization, specific relaxation processes in the excited state, and its stimulated emission abi...

As one of the most important minerals in the body, potassium is vital for the heart and neurons. Methods that can non‐invasively and accurately monitor changes in potassium balances would benefit disease diagnoses as well as offer insight into pathologies. Among the sensing approaches, fluorescent probes serve as a unique detection method for its s...

Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent‐induced apoptosis. A boron‐dipyrromethene (BODIPY) chromophore‐based triarylsulfonium photoacid generator (BD‐PAG) was used to target mitochon...

The Cover Feature depicts photoacid generators, light‐responsive organic molecules that release protons in a light‐guided manner and subsequently activate proximal acid‐sensing ion channels at the cellular level with minimal invasiveness. More information can be found in the Communication by Kevin D. Belfield, Yuanwei Zhang and co‐workers.

Acid‐sensing ion channels (ASICs), present in both central and peripheral neurons, respond to changes in extracellular protons. They play important roles in many symptoms and diseases, such as pain, ischemic stroke and neurodegenerative diseases. Herein, we report a novel approach to activate ASICs with the precision of light using organic photoaci...

Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-stablished fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present...

A small set of four new fluorenyl chromophores (5-5a-c) was accomplished by stepwise nucleophilic substitution, Friedel-Crafts acylation, Ullman coupling, aldol condensation and cyclization reactions. The fluorene moiety was substituted at 2,7,9 and 9′ positions with diverse groups. The synthesized derivatives were characterized by FTIR, 1H-NMR and...

Mitochondria are essential targets for treatment of diseases with mitochondrial disorders such as diabetes, cancer, cardiovascular and neurodegenerative disease. Mitochondria penetrating peptides (MPPs) are composed of cationic and hydrophobic amino acids that can target and permeate the mitochondrial membrane. Herein, a novel D-argine phenylalanin...

The electronic properties of neutral 2,4-bis(4-bis(2-hydroxyethyl) amino-2-hydroxy-6-(2- (2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)squaraine (1) and charged 2-((3- octadecylbenzothiazol-2(3H)-ylidene)methyl)-3-oxo-4-((3-(4-(pyridinium-1-yl)butyl)benzothiazol-3-ium-2-yl)methylene)cyclobut-1-enolate iodide (2) squaraine derivatives were analyzed based...

The efficient clearance of the interstitial waste metabolites is essential for the normal maintenance of brain homeostasis. The brain lacks the lymphatic clearance system. Thus, the drainage of waste metabolites in the brain is dependent on a slow flow of cerebrospinal fluid (CSF) system. Glymphatic system claims the direct bulk flow transport of s...

The features of the electronic structures of a series of new styryl dye bases were investigated and characterized by their steady-state and time-resolved spectral properties, including femtosecond transient absorption spepctroscopy and DFT quantum chemical calculations. The steady-state absorption and fluorescence spectra, fluorescence quantum yiel...

Capitalizing on the nucleophilic addition of hydrazine toward the central cyclobutenyl core and affinity of aldehydes to hydrazine group, two water-soluble squaraine dyes (SQOH and SQPY) were synthesized as sensitive colorimetric and fluorescent chemosensors for aldehydes. The color change from blue to colorless and back to blue these sensors under...

A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicin...

Squaraine dyes AM‐1′ and AM‐1 bearing adamantyl termini were synthesized and spectroscopically characterized. AM‐1′ exhibited intense absorption and sharp emission in the far‐red to near‐infrared (NIR) spectral region. The degenerate two‐photon absorption (2PA) spectrum of AM‐1′ was obtained over a broad spectral range with a maximum cross section...

A comprehensive experimental and theoretical study of linear photophysical properties, excited state relaxation, two-photon absorption, and stimulated emission spectra of the symmetrical fluorene derivative 2,2'-((1E,1'E)-(9,9-diethyl-9H-fluorene-2,7-diyl)bis(ethene-2,1-diyl))bis(1-methyl-1H-pyrrole) (1) are presented. The steady-state absorption,...

With the objective of developing new near-infrared fluorescent probes and understanding the effect molecular structure exerts on physical properties, a series of aniline-based squaraine dyes with different number and position of methoxy substituents adjacent to the squaraine core was synthesized and investigated. Using both computational and experi...

Through in vivo two-photon fluorescence microscopy experiments, the clearance of water-insoluble large size cerebrospinal fluid metabolites regulated by brain arterial endothelium and smooth muscle cells through perivascular dynamic exchange was studied.

A series of small organic molecules were synthesized by exploiting the bay and imide positions of the perylene nucleus. The synthesized compounds 1–11 were characterized by spectroscopic and elemental analyses. These molecules show yellowish color in solution and are highly soluble in dichloromethane. Compound 7 shows a bandgap of 1.7 eV and a Stok...

Delivery of hydrophobic materials in biological systems, for example, contrast agents or drugs, is an obdurate challenge, severely restricting the use of materials with otherwise advantageous properties. The synthesis and characterization of a highly stable and water-soluble nano-vesicle, referred to as a quatsome (QS, vesicle prepared from cholest...

A comprehensive study of the photophysical properties of triethylene glycol monomethyl ether (TEG)-substituted squaraine dye SQ1 is presented. SQ1 exhibits strong absorption and intense fluorescence emission in the far-red spectral region and high photostability. Interestingly, bis-tegylated SQ1 was characterized to exhibit properties different fro...

Fluorescent contrast agents are important tools in cell biology and medical imaging due to their high sensitivity and relative availability. Diketopyrrolopyrrole (DPP) derivatives have been recently studied for applications in bioimaging but certain drawbacks due to their inherent structure have stifled the progress towards their widespread impleme...

Stable, water-soluble nanovesicles, prepared from amphiphilic quaternary amines (Quatsomes), encapsulating a fluorene-based probe is reported. Examination of its cellular distribution revealed its potential utility as a fluorescent lysosome tracker.

An RGD-peptide functionalized nanoparticle carrier encapsulating a squaraine probe that can be excited via two-photon absorption in the NIR is reported. Efficient cellular and tissue imaging demonstrate its potential for biological applications.

Two cationic conjugated polyelectrolytes (CPEs) based on poly(phenylene ethynylene) are found to exhibit efficient 2-photon excited fluorescence. Specially, the CPEs aggregates display enhanced 2-photon absorption compared to the non-aggregated states. The CPEs are used as 2-photon absorption sensitizers to harvest light and amplify the fluorescenc...

A series of dyes 2–5 based on 5-thienyl-2,1,3-benzothiadiazole and 5-thienyl-2,1,3-benzoselenadiazole cores were synthesized as near-infrared-emitting two-photon-absorbing fluorophores. Fluorescence maxima wavelengths as long as 714 nm and quantum yields as high as 0.67 were realized. The fluorescence quantum yields of dyes 2–4 were nearly constant...

With the scientific community becoming increasingly aware of the need for greener products and methodologies, the optimization of synthetic design is of greater importance. Building on experimental data collected from a synthesized guaiazulene derivative, a series of analogous structures were investigated with time-dependent density functional theo...

Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative ox...

A new halogenated BODIPY derivative was designed as a singlet oxygen photosensitizer (PS) for use as a photodynamic therapy (PDT) agent and its photophysical properties were characterized. The PS, having two iodine atom substituents, exhibited low fluorescence quantum yield (ΦFL) of 0.02 and high singlet oxygen generation quantum yield (Φ∆) of 0.93...

The steady-state and time-resolved linear spectral properties, two-photon absorption spectra and fast relaxation processes in the excited states of styryl base-type derivatives were investigated. The nature of linear absorption, fluorescence and excitation anisotropy spectra were analyzed in solvents of different polarity at room temperature and sp...

A highly water-soluble, fluorescence "turn-on" sensor for Ca2+ is reported. The sensor affords high selectivity in sensing Ca2+ over other biologically important metal cations. The dissociation constant of the sensor in binding Ca2+ is 0.92 mM. Fluorescence microscopy experiments demonstrate that the sensor is cell-impermeable and capable of detect...

A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce potential photot...

We investigated and validated a novel method to develop ultrathin lensed fiber-optic (LFO) probes for optical coherence tomography (OCT) imaging. We made the LFO probe by attaching a segment of no core fiber (NCF) to the distal end of a single mode fiber (SMF) and generating a curved surface at the tip of the NCF using the electric arc of a fusion...

Imaging biological samples with two-photon fluorescence (2PF) microscopy has the unique advantage of resulting high contrast 3D resolution subcellular image that can reach up to several millimeters depth. 2PF probes that absorb and emit at near IR region need to be developed. Two-photon excitation (2PE) wavelengths are less concerned as 2PE uses wa...

A water-soluble fluorescent mitochondrial targeting probe is reported. The probe bears a BODIPY-based fluorophore, two triphenylphosphonium (TPP) groups as mitochondrial targeting moieties, and two PEG groups to increase water solubility and enhance biocompatibility. As a mitochondria-selective fluorescent probe, the new BODIPY derivative exhibited...

It is difficult to overstate the physiological importance of potassium for life as its indispensable roles in a variety of biological processes are widely known. As a result, efficient methods for determining physiological levels of potassium are of paramount importance. Despite this, relatively few K+ fluorescence sensors have been reported, with...

Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue...

A new mitochondrial targeting fluorescent probe is designed, synthesized, characterized, and investigated. The probe is composed of three moieties, a BODIPY platform working as the fluorophore, two triphenylphosphonium (TPP) groups serving as mitochondrial targeting moiety, and two long highly hydrophilic polyethylene glycol (PEG) chains to increas...

A comprehensive study of photophysical and photochemical properties of an unsymmetrical fluorene derivative is presented, including linear absorption, fluorescence excitation anisotropy, photochemical stability, steady-state fluorescence, and fluorescence lifetimes in organic solvents of different polarity. Nonlinear optical properties were investi...

Two indole-based squaraine dyes, bearing two pyrenyl groups through vinyl or ethynyl linkers, were synthesized with the aim of enhancing the intramolecular charge transfer interaction in addition to improving their optical properties. The absorption and emission properties of these derivatives were determined to gain insight into the intensity of t...

Optical coherence tomography (OCT) signal can provide microscopic characterization of biological tissue and assist clinical decision making in real-time. However, raw OCT data is noisy and complicated. It is challenging to extract information that is directly related to the pathological status of tissue through visual inspection on huge volume of O...

With the scientific community becoming increasingly aware of the need for greener products and methodologies, the optimization of synthetic design is of greater importance. Building on experimental data collected from a synthesized guaiazulene derivative, a series of analogous structures were investigated with time-dependent density functional theo...

With the scientific community becoming increasingly aware of the need for greener products and methodologies, the optimization of synthetic design is of greater importance. Building on experimental data collected from a synthesized guaiazulene derivative, a series of analogous structures were investigated with time-dependent density functional theo...

Speckle decorrelation analysis of optical coherence tomography (OCT) signal has been used in motion tracking. In our previous study, we demonstrated that cross-correlation coefficient (XCC) between Ascans had an explicit functional dependency on the magnitude of lateral displacement (δx). In this study, we evaluated the sensitivity of speckle motio...

Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent l-arginine (R), glycine (G) and l-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue...

A new two-photon excited fluorescent K(+) sensor is reported. The sensor comprises three moieties, a highly selective K(+) chelator as the K(+) recognition unit, a boron-dipyrromethene (BODIPY) derivative modified with phenylethynyl groups as the fluorophore, and two polyethylene glycol chains to afford water solubility. The sensor displays very hi...

Two new two-photon absorbing near-infrared (NIR) emitting 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives, DDC and SDC, were designed for one- and two-photon fluorescence microscopy imaging. Linear and nonlinear photophysical properties, including UV/Vis absorption, fluorescence, excitation anisotropy, photostability, and two-photon...

In addition to their use as colorants in diet and cosmetics, various natural dyes possess photophysical properties that could enable their use as modular building blocks for preparing eco-friendly and non-toxic chromophores. Among natural pigments, guaiazulene holds great potential due to its unique optical and electronic properties. Thus, in order...

A series of new molecular materials with varying carbazole and fluorene contents were prepared employing Suzuki coupling and their properties were compared. A variation of the core nucleus from fluorene to carbazole was a key point to study its effect on thermal, optical and electrochemical properties. The materials were characterized by FTIR, 1H-,...

The synthesis and comprehensive linear photophysical and nonlinear optical characterization of new diketopyrrolopyrrole derivatives, 2-(2-ethylhexyl)-3,6-di(pyridin-2-yl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (1) and 2-(10-azidodecyl)-3,6-di(thiophen-2-yl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (2), are reported. The nature of the main lin...

Application of nanoparticles for controlling plant pathogens is a rapidly emerging area in plant disease management, and nanoparticles synthesis methods that are economical and eco-friendly are extensively investigated. In this project, we investigated the potential of silver nanoparticles (AgNPs) synthesized with aqueous extract of Artemisia absin...

We report the one-pot synthesis, 1D and 2D NMR characterization, and UV/Vis study of a series of cyclopenta[ef]heptalenes 4a–c that exhibit strong stimuli-responsive behavior, with a tunable energy gap as a result of perturbation of HOMO, LUMO, and LUMO+1 energies upon doping/dedoping with TFA/Et3N. The approach employed allows for the extension of...

The synthesis, linear photophysical characterization, and nonlinear optical properties of two new symmetrical fluorene-containing quinolizinium derivatives, 2,8-bis((E)-2-(7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-yl)vinyl)quinolizinium hexafluorophosphate (1) and 2,8-bis((E)-2-(7-((7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-yl)ethynyl)-9,9-dihexy...

In this report, a vastly improved method for the synthesis of [2.2.3]-triazacryptand (TAC), an excellent K+-selective cryptand, is disclosed, which provides a shorter synthetic route with > fivefold higher overall yield. On the basis of the improved synthesis, a TAC-BODIPY conjugate was developed for K+ sensing. TAC-BODIPY is a fluorescence turn-on...

A novel boron-dipyrromethene (BODIPY) based fluorescence turn-on sensor for detecting Fe3+ in aqueous media is reported with 23-fold fluorescence enhancement. The sensor is comprised of a combination of BODIPY fluorophore and a new Fe3+-recognizing cryptand that exhibits high selectivity, sensitivity, and reversibility toward Fe3+ detection. Cell i...

The luminescent properties of lanthanides have been evident for a long time. Despite this, the increased interest in two-photon absorption has not provided many practical avenues to access these long-lived luminescent signals. This study took on the synthesis and characterization of a novel fluorene-based donor-acceptor ligand and a series of lanth...

The one and two-photon photophysical properties of two pyrene-terminated squaraine dyes were investigated in THF and DCM. Neither compound showed any significant solvatochromic behavior with the change in solvent polarity, though a roughly 50% increase in the fluorescence quantum yield and the extinction coefficient was realized through moving from...

Molecular symmetry plays an important role in physical characterizations, as it influences the spectra obtained for a compound. However results can sometimes be counterintuitive due to unpredictable characteristics of a molecule. Photophyscial characterization of a centrosymmetrical indacene-1,3,5,7(2H,6H)-tetraone, or Janus dione, derivative revea...

A fluorene-based donor-acceptor ligand was successfully employed to sensitize visible and near-IR emitting lanthanide centers. The ligand construct is based on a donor-π-acceptor architecture with diphenylamino acting as the donor and a fluorenyl π bridge derivatized with a trifluoroacetonate moiety acting as both a strong acceptor and the classic...

Disclosed are fluorescent compounds useful as intracellular pH probes. In particular, the invention teaches a two-photon absorbing, water soluble, fluorescent compound, a fluorene derivative, which is effective as a near-neutral pH indicator and particularly as an intracellular probe. A method for chemical synthesis of the claimed compounds is prov...

New symmetrical fluorene-containing derivatives with a benzothiadiazole (BTD) central core, 4,7-bis(5-(9,9-didecyl-7-(phenylsulfonyl)-9H-fluoren-2-yl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole (1) and 4,7-bis(5′-(9,9-didecyl-7-(phenylsulfonyl)-9H-fluoren-2-yl)-2,2′-bithiophen-5-yl)benzo[c][1,2,5]thiadiazole (2), were prepared, and multifarious linear...

A comprehensive investigation of the electronic structure and fast relaxation processes in the excited states of new styryl base-type derivatives was performed using steady-state, pico-, and femtosecond time-resolved spectroscopic techniques. Linear photophysical parameters of new compounds, including steady-state absorption, fluorescence, and exci...

Deoxyribonucleoside-modified squaraines were synthesized by Sonogashira coupling reactions using an unsymmetrical, terminal alkynylated benzothiazolium squaraine dye. These non-natural nucleosides exhibited fluorescent ‘turn-on’ properties in viscous conditions with an enhancement of >300-fold. The viscosity-dependent fluorescence enhancement was a...

A squaraine dye is tested for novel application in a near-infrared-active organic photovoltaic cell that is subsequently optimized to obtain a power conversion efficiency of 2.4 ± 0.3%. The optimization utilizes an Alq3 buffer layer and macroscopic structure control through the addition of co-solvents in the spin-casting process. Co-solvent additio...

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A rapid, straightforward method for measuring the two-photon absorption cross sections in liquid samples based on both the accumulative photo-thermal effect and the Rayleigh interferometery is described and demonstrated. This technique combines the sensitivity of the thermal lens approach and the accuracy of interferometry techniques. Focusing a hi...

A fluorene-bridged squaraine dimer (SD-FLU-SD) was designed with the purpose of combining various chromophores in one molecule and enhancing its two-photon absorption properties using intra-and interchromophore transitions. Linear and nonlinear absorption properties of SD-FLU-SD were investigated with the goals of understanding the nature of one-an...

The synthesis, linear photophysical, two-photon absorption (2PA), femtosecond transient absorption, and superfluorescence properties of a new symmetrical squaraine derivative (1) are reported. Steady-state linear spectral and photochemical properties, fluorescence lifetimes, and excitation anisotropy of 1 were investigated in various organic solven...