Charles Michael Drain

• Ph.D.
• City University of New York - Hunter College

Technetium‐99 is a prevalent fission product from nuclear waste. The long half‐life (211,000 yr) and environmental mobility of pertechnetate (TcO4⁻) render Tc particularly challenging to isolate and stabilize. Here we present two approaches for development of potential wasteforms using titanium dioxide, TiO2. Approach 1 is a low temperature chemica...

Uranium-238 (238U), a long-lived radiometal, is widespread in the environment because of both naturally occurring processes and anthropogenic processes. The ingestion or inhalation of large amounts of U is a major threat to humans, and its toxicity is considered mostly chemical rather than radiological. Therefore, a way to remove uranium ingested b...

Synthetic chlorins are not only fluorescent, the modulation of the tetrapyrrole system can also chelate metal ions. Conjugation of linkers at their pyrrolidines allows for conjugation to bio-molecules to create target specificity. By altering these chemo-photophysical properties, this work facilitates the use of chlorins in fluorescent imaging and...

Waterways have histories of being contaminated by heavy and/or radioactive metals produced by industrial processes. Natural radioisotopes of uranium (²³⁸U, ²³⁵U and ²³⁴U), long-lived radiometals, are widespread in the environment as a result of both naturally occurring processes and anthropogenic processes. Uranium is considered a major threat to h...

Polyacetylene materials, particularly two-dimensional polyacetylene thin films, have widespread applications in modern electronics and energy harvesting devices. One way to fabricate polyacetylene thin films is to attach functional groups that can covalently bond to underlying surfaces. Thiol-terminated polydiacetylenes, with their highly conjugate...

Herein we describe the design, efficient synthesis, and photophysical properties of two macrocycle dyes for cancer theranostics. This study compares a glycosylated chlorin with a glycosylated phthalocyanine designed to specifically target cancer, wherein the photophysical properties enable both fluorescence imaging and the sensitization of the form...

Distortion of nominally planar phthalocyanine macrocycles affects the excited state dynamics in that most of the excited‐state energy decays through internal conversion. A click‐type annulation reaction on a perfluorophthalocyanine platform appending a seven‐membered ring to the β‐positions on one or more of the isoindoles distorts the macrocycle a...

The ligand 3,4,3-LI(1,2-HOPO) or HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone, has been shown to be an efficient and stable chelator for Zr(IV) and the bifunctional derivative, p-SCN-Bn-HOPO, can be conjugated to antibodies via the isothiocyanate group and radiolabeled with 89Zr at room temperature. The positron emission...

Photodynamic therapy (PDT) is a non-invasive treatment widely applied to different cancers. The goal of PDT is the photo-induced destruction of cancer cells by the activation of different cell death mechanisms, including apoptosis and/or necrosis. Recent efforts focusing on understanding the mechanisms of cell death activated by PDT find that it de...

Self-assembled monolayers of thiol terminated conjugated diacetylenes can be cross-linked using ultraviolet light to form highly conjugated polydiacetylenic conductive monolayers [1]; however, the reported syntheses of the diacetylene monomers present numerous problems that prevent the wide spread application of these in functional materials. We re...

Chlorins have unique photophysical properties that are exploited in diverse biological and materials applications. De novo chlorin synthesis with specific exocyclic motifs can be challenging and many are not stable to photobleaching and/or oxidation. A facile approach to a stable synthetic chlorin with a fused N-methyl pyrrolidine uses cyclo additi...

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced n...

A physical organic chemistry experiment is described for second-year college students. Students performed nucleophilic aromatic substitution (NAS) reactions on 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin (TPPF20) using three different nucleophiles. Substitution occurs preferentially at the 4-position (para) because it is thermodynamic...

A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright...

Supplementary figures and tables.

Nitro-porphyrins are an important class of commercial dyes with a range of potential applications. The nitro group is known to dramatically affect the photophysics of the porphyrin, but there are few systematic investigations of the contributing factors. To address this deficiency, we present spectroscopic studies of a series of nitro-porphyrins, a...

Chemical exfoliation of graphite under strong oxidizing conditions yields graphene oxide nanosheets with oxy functional groups on the carbon basal plane. The importance of ozone in the chemical oxidation mechanism of graphite by the widely-used Hummers' method has been largely overlooked. Herein we demonstrate that the ozonolysis of graphite leads...

Different gold-nanoparticle shapes can be produced by a new surfactant-free synthetic strategy presented by Moritz F. Kircher and co-workers in article number 1605622. Gold-nanorod formation in this method is driven by re-entrant groove defects on the end facets. Nanoparticles synthesized by this approach demonstrate excellent surface-enhanced Rama...

Here we report on the effect of local molecular organization or “tertiary structure” on the charge transport properties of thiol-tethered tetraphenylporphyrin (ZnTPPF4-SC5SH) nanoscale clusters of ca. 5 nm in lateral dimension embedded within a dodecanethiol (C12) monolayer on Au(111). The structure of the clusters in the mixed monolayers and their...

Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To...

Glucose utilization of cancer cells growing in monolayers at 48 h after plating with seeding densities of 5,000 HCT-116 cells per well, 15,000 MCF-7 cells per well, 20,000 UM-UC-3 cells per well and 20,000 HeLa cells per well. The amount of glucose (nmol) was estimated using the fluorescent glucose analog 2NBDG and the results were normalized for m...

Cytotoxicity of PBS solution containing 0.5% DMSO (v/v) in monolayer cultures at different incubation times (0.5, 1, 2 and 4h). The percentage of cytotoxicity was calculated relatively to control cells (cells incubated with medium). Data are means ± S.D. of at least three independent experiments performed in triplicate. (TIF)

Non-dark toxicity of PorGlu4 at 9 μM and uptake time of 4 h in spheroid cultures as determined using the LDH assay. The percentage of cytotoxicity was calculated relatively to control cells (untreated cells). Data are means ± S.D. of at least three independent experiments performed in triplicate. (TIF)

Quantification of DCF fluorescence increase as a measure of ROS production after PDT in cancer cells growing in monolayers, after PDT with PorGlu4. ROS levels are expressed as a ratio of the levels found on the respective control cells and normalized to mg of protein. Data are means ± S.D. of at least three independent experiments performed in trip...

Lactate utilization of cancer cells growing in monolayers at 48 h after plating with seeding densities of 5,000 HCT-116 cells per well, 15,000 MCF-7 cells per well, 20,000 UM-UC-3 cells per well and 20,000 HeLa cells per well. The amount of lactate (nmol) was estimated using an enzymatic assay and the results were normalized for mg of protein. Data...

Quantitative analysis of GLUT1 (normalized to β-actin) in spheroid cultures expressed as a ratio of the levels found in HeLa spheroids. Data are means ± S.D. of at least five independent experiments. *P< 0.05, ***P< 0.001 compared to GLUT1 protein levels in HeLa spheroids. (TIF)

Non-dark toxicity of PorGlu4 at different concentrations (0, 2.25, 4.5 and 9 μM) and uptake time of 4h, in monolayer cultures. The percentage of cytotoxicity was calculated relatively to control cells (untreated cells). Data are means ± S.D. of at least three independent experiments performed in triplicate. (TIF)

Cytotoxicity at 24 h after PDT with PorGlu4 in cancer cells growing in monolayers, determined using the MTT assay. Data are means ± S.D. of at least three independent experiments performed in triplicate. **P< 0.01, ***P< 0.001 compared to MTT reduction (%) of control cells (untreated cells). (TIF)

Quantification of DCF fluorescence increase (as a measure of ROS production after PDT) in cancer cells growing in spheroids, after PDT with PorGlu4. ROS levels are expressed as a ratio of the levels found on the respective control cells and normalized to mg of protein. Data are means ± S.D. of at least three independent experiments performed in tri...

HCT-116 spheroid size and cellular characteristics as a function of age (24, 48 and 72h) and number of platted cells (2,500, 5,000, 10,000 and 20,000 cells per well). (TIF)

MCF-7 spheroid size and cellular characteristics as a function of age (24, 48 and 72h) and number of platted cells (5,000, 10,000, 15,000 and 20,000 cells per well). (TIF)

HeLa spheroid size and cellular characteristics as a function of age (24, 48 and 72h) and number of platted cells (2,500, 5,000, 10,000 and 20,000 cells per well). (TIF)

Quantitative analysis of galectin-1 (normalized to β-actin) in spheroid cultures expressed as a ratio of the levels found in HeLa spheroids. Data are means ± S.D. of at least five independent experiments. **P< 0.01, ***P< 0.001 compared to galectin-1 protein levels in HeLa spheroids. (TIF)

Chemical structure of PorGlu4. (TIF)

Intracellular uptake of PorGlu4 by HCT-116, MCF-7, UM-UC-3 and HeLamonolayer cultures. The concentration of PorGlu4 was determined by fluorescence spectroscopy (λexcitation at 410 nm and λemission at 702 nm) after incubation of cancer cells with 0, 2.25, 4.5 or 9 μM of PorGlu4 for 0.5, 1, 2 or 4 h and the results normalized to protein quantity. Dat...

Intracellular uptake of PorGlu4 by HCT-116, MCF-7, UM-UC-3 and HeLa growing in monolayer or spheroid cultures. The concentration of PorGlu4 was determined by fluorescence spectroscopy after incubation of cancer cells with 9 μM PorGlu4 during 4 h (λexcitation at 410 nm and λemission at 702 nm) and the results normalized to protein quantity. Data are...

Cytotoxicity at 24 h after PDT with PorGlu4 in cancer cells growing in spheroids, determined using the LDH assay. Data are means ± S.D. of at least three independent experiments performed in triplicate. *P< 0.05, **P< 0.01, ***P< 0.001 compared to LDH reduction (%) of control cells (untreated cells). (TIF)

Quantification of DCF fluorescence increase as a measure of endogenous ROS in cancer cells growing as monolayers or spheroids. ROS levels are expressed as a ratio of the levels found on the respective cell line growing in monolayers. Data are means ± S.D. of at least three independent experiments performed in triplicate. **P< 0.01, ***P< 0.001 comp...

UM-UC-3 spheroid size and cellular characteristics as a function of age (24, 48 and 72h) and number of platted cells (2,500, 5,000, 10,000 and 20,000 cells per well). (TIF)

Gold nanoparticles have unique properties that are highly dependent on their shape and size. Synthetic methods that enable precise control over nanoparticle morphology currently require shape-directing agents such as surfactants or polymers that force growth in a particular direction by adsorbing to specific crystal facets. These auxiliary reagents...

A multifunctional chlorin platform appended with four short polyethylene glycols and a carboxylate-linker allows rapid conjugation to biotargeting motifs such as proteins and oligonucleotides. The stability and photophysical properties of the chlorin enable development of diagnostics, imaging, molecular tracking, and theranostics.

This expansive and practical textbook contains organic chemistry experiments for teaching in the laboratory at the undergraduate level covering a range of functional group transformations and key organic reactions.The editorial team have collected contributions from around the world and standardized them for publication. Each experiment will explor...

Nuclear medicine utilizes ionizing radiation for both in vivo diagnosis and therapy. Ionizing radiation comes from a variety of sources, including X-rays, beam therapy, brachytherapy, and various injected radionuclides. While positron emission tomography and single-photon emission computed tomography remain clinical mainstays, optical readouts of i...

Nanoparticles labeled with radiometals enable whole-body nuclear imaging and therapy. While chelating agents are commonly used to radiolabel biomolecules, nanoparticles offer the advantage of attaching a radiometal directly to the nanoparticle itself without the need of such agents. We previously demonstrated that direct radiolabeling of silica nan...

Organic nanoparticles (ONp) of an Fe(III) porphyrin appended with four N-polyethyleneglyco-pyridinium moieties prepared in acetonitrile were deposited onto hydrophilic or hydrophobic Si surfaces. Self-organized by intermolecular interactions, ONp reorganize in response to environmental changes. Mechanisms for the control of nanoparticle morphologie...

Directing molecular devices into pre-designed integrated electronic circuits while enforcing selectivity and hierarchy is an inherent challenge for molecular electronics. Here we explore ways to direct the assembly of electrically-active molecular monolayers into specific locations as well as controlling their internal organization. We have accompl...

A summary of photonic materials based on porphyrinoids from the laboratory of Charles Michael Drain

Summary of the biomedical applications of porphyrins and phthalocyanines from the Hunter College laboratory of Charles Michael Drain

A summary of the synthesis and applications of porphryinoids in the laboratory of Charles Michael Drain.

Porphyrinoids are robust heterocyclic dyes studied extensively for their applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include their use as phthalocyanine dyes in optical discs,...

The use of glycosylated porphyrins, phthalocyanines, and other porphyrinoids for diagnostics and therapeutics are discussed. Porphyrins and phthalocyanines (Pcs) are the most common and efficient photosensitizers (PSs) used in photodynamic therapy (PDT) due to their absorption in the visible range of the electromagnetic spectrum, long-lived triplet...

The rational design of enhanced chlorins in comparison to chlorophyll for distinct bio-physical uses in fluorescent imaging, chelators for PET and bio-targeting with the use of amenable linkers.

When tunneling is the dominant mechanism of charge transport in a molecular junction, the conductivity of the junction is largely insensitive to chemical and structural perturbations which do not impact the overall length of the junction. This severely hampers the seemingly limitless potential of molecules to modulate charge transport at interfaces...

Chelator-free nanoparticles for intrinsic radiolabeling are highly desirable for whole-body imaging and therapeutic applications. Several reports have successfully demonstrated the principle of intrinsic radiolabeling. However, the work done to date has suffered from much of the same specificity issues as conventional molecular chelators, insofar a...

Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of the...

The photophysical properties of a chlorin, isobacteriochlorin, and bacteriochlorin built on a core tetrapentafluorophenylporphyrin (TPPF20 ) and the non-hydrolysable para thioglycosylated conjugates of these chromophores are presented. The photophysical characterization of these compounds was done in three different solvents to correlate to differe...

The protruding oxophilic central metal ion of Zr(IV) porphyrinoids facilitates axial coordination to the oxygen bearing functional groups on graphene oxide (GO) surfaces to result in new supramolecular photonic materials with high dye loading especially on edges and large defects. The reaction proceeds at room temperature with GO dispersed in tetra...

Clicking thiols onto a core fluorous phthalocyanine (Pc) platform yields alkyl and fluoroalkyl derivatives. The Zn(II) Pc with 16 thioalkanes self-organizes with fullerene C60 into nearly monodispersed nanoparticles when cast on ITO surfaces. Particle size and surface density is controlled by varying the Pc/fullerene ratio and concentration. Fluore...

In the current study we have synthesized a phthalocyanine bearing 16 long alkane moieties to promote self-organization on a surface and showed how to pattern ITO electrode with a blend of this phthalocyanine and fullerene C60, using a simple electrode immersion method. The particle size and surface density is controlled by varying the ratio of chro...

The current study focuses on the design, construction, and characterization of new photonic dye materials composed of phthalocyanine dyes appended with long fluorous alkanes. While the overarching goal is to develop photonic dyes for urban solar energy harvesting and for photodynamic therapies, the immediate goal is to develop the synthetic strateg...

Systematic changes in the exocyclic substiution of core phthalocyanine platform tune the absorption properties to yield commercially viable dyes that function as the primary light absorbers in organic bulk heterojunction solar cells. Blends of these complementary phthalocyanines absorb a broader portion of the solar spectrum compared to a single dy...

Ternary phthalocyanine–metal–polyoxometalate (Pc–M–POM) complexes were synthesized and characterized. Group (IV) Hf or Zr ions reside outside the plane of the macrocycle and are coordinated to both the phthalocyanine and the lacunary polyoxometalate. The metal ions mediate the electronic communication between the Pc and the POM.

Metalloporphyrin and metallophthalocyanine dyes ligating Hf(IV) and Zr(IV) ions bind to semiconductor oxide surfaces such as TiO 2 via the protruding group IV metal ions. The use of oxophilic metal ions with large ionic radii that protrude from the macrocycle is a unique mode of attaching chromophores to oxide surfaces in the design of dye-sensitiz...

Self-organized organic nanoparticles (ONP) are adaptive to the environmental reaction conditions. ONP of fluorous alkyl iron(III) porphyrin catalytically oxidize cyclohexene to the allylic oxidation products. In contrast, the solvated metalloporphyrin yields both allylic oxidation and epoxidation products. The ONP system facilitates a greener react...

A simple, high yield, two-step synthesis yields a porphyrin dimer linked by a flexible dithiol tether that preferentially binds fullerene C(70) over C(60) in toluene solution. The complex forms stable aggregates when cast on glass.

Organic nanoparticles of metalloporphyrins can be a versatile catalyst for the selective oxidation of alkenes and other hydrocarbons. The catalytic activity of the metalloporphyrin depends on the nature of the central metal atom, peripheral groups, and the architecture of the porphyrin macrocycle. Herein, we report the catalytic activity of organic...

Porphyrins are heterocyclic macrocycles that are extensively studied as functional materials and components of devices in several fields of science because of their unique and tunable characteristics. The periphery of the ring can be functionalized with a variety of substituents that modulate both the photophysical and the materials properties. Bec...

Gold nanoparticles (AuNPs) have been exploited for a wide range of potential applications, including drug delivery systems, catalysts, optical sensors and antimicrobial agents [1-5]. However, the harsh conditions employed in several synthetic approaches has forced researchers to investigate milder routes [6]. Biological macromolecules such as prote...

A water soluble zinc(II) phthalocyanine symmetrically appended with eight thioglucose units was synthesized from commercially available hexadecafluorophthalocyaninatozinc(II) by controlled nucleophilic substitution of the peripheral fluoro groups. The photophysical properties and cancer cell uptake studies of this nonhydrolyzable thioglycosylated p...

Metallic and non-metallic nanoparticles (NPs), ranging in size from 1–200 nm, have unique functional properties that differ from their bulk materials and their component atoms or molecules. These unique properties have driven the demand for nano-sized materials and new methods to synthesize NPs, which are used in drug delivery systems, bio-imaging...

Porphyrins appended with four rigid hydrogen bonding motifs on the meso positions were synthesized and self-assembled into a cofacial cage with four complementary bis(decyl)melamine units in dry solvents. The hydrocarbon chains on the melamine mediate the formation of nanofilms on surfaces as the solvent slowly evaporates.

As nanolithography becomes increasingly important in technology and daily life, a variety of inexpensive and creative methods toward communicating the concepts underpinning these processes in the classroom are necessary. An experiment is described that uses simple CD-Rs, C-clamps, an oven, and a freezer to provide concrete examples and insights int...

Sequential dipping of indium-tin oxide electrodes into solutions of tetra cationic porphyrins and tetra anionic polyoxometalates results in the controlled formation of nm thick films. The potential applications of these robust films on electrodes range from catalysts to sensors. This chapter focuses on the electrochemistry of the multilayered films...

A characteristic of cancer cells is the generation of lactate from glucose in spite of adequate oxygen for oxidative phosphorylation. This property - known as the "Warburg effect" or aerobic glycolysis - contrasts with anaerobic glycolysis, which is triggered in hypoxic normal cells. The Warburg effect is thought to provide a means for cancer cells...

Multifunctional molecules bearing different dyes, such as donor-acceptor systems, synthesized by covalent chemistry have provided a wealth of information on the fundamental nature of electron and energy transfer in organic systems and there is a growing literature on the materials properties of dyes on surfaces. However, in the vast majority of cas...

The proposal that molecules can perform electronic functions in devices such as diodes, rectifiers, wires, capacitors, or serve as functional materials for electronic or magnetic memory, has stimulated intense research across physics, chemistry, and engineering for over 35 years. Because biology uses porphyrins and metalloporphyrins as catalysts, s...

The facile synthesis and photophysical properties of three nonhydrolyzable thioglycosylated porphyrinoids are reported. Starting from meso-perfluorophenylporphyrin, the nonhydrolyzable thioglycosylated porphyrin (PGlc₄), chlorin (CGlc₄), isobacteriochlorin (IGlc₄), and bacteriochlorin (BGlc₄) can be made in 2-3 steps. The ability to append a wide r...

New concepts in the design and function of organic dyes as sensitizers for solar energy harvesting are needed. Simple porphyrin dyes offer cost effective synthesis and long-term stability, but new modes of incorporation into devices are needed to increase the efficiency of charge separation that drives any photonic device designed to harvest light....

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Porphyrins bearing uracyl motifs at the four meso positions self-organize via homo-complementary hydrogen bonds and pi-stacking into nanofibers, nanorods and thin films on mica and glass surfaces depending on deposition conditions.