Glaser Group Research

Boldness has genius, power and magic in it. Johann Wolfgang von Goethe

Chemistry of Anisotropic Media.
Organic, Theoretical, and Materials Chemistry. Chemistry Education.
Descriptive Realism. Make, measure, and think with theory.

Projects 1. DNA Base Deamination and Cross-Link Formation.
2. Polar Order in Crystalline Organic Molecular Materials.
3. Chemistry in Interstellar and Intergalactic Media.
4. Nucleophilic Additions to Heterocumulenes.
5. Electronic Structure Theory: Potential Energy Surfaces and Dynamics.
6. Chemistry is in the News: Collaboration, Communication, Community and Society.

We are studying topics in organic, organometallic, and bio-organic chemistry with modern theoretical methods in combination with laboratory experimentation. Several projects are pursued in collaboration with groups elsewhere in the US and in Europe creating opportunities for student exchanges. The interdisciplinary approach to pertinent problems exposes students to a broad spectrum of diverse techniques and provides a unique preparation for careers in modern research areas positioned at the interphases between the classical disciplines.

1. DNA Base Deamination and Cross-Link Formation

Methods: Chemical & Enzymatic Synthesis, Oligonucleotide Chemistry, Non-Natural DNA Bases, Labeling Techniques (18-O, 17-O), HPLC, LC/MS, NMR Studies (1-H, 13-C, 17-O, 18-O isotopic shifts on 13-C), Covalent and Dative Bonding, Ab Initio Theory, Molecular Dynamics

We have been interested in two types of deaminations and their relation to modifications of DNA bases: The deamination of amines and their role in the alkylation of DNA and the deamination of the DNA bases guanine, cytosine and adenine. These processes lead to genomic instability. Much of our work on oxidative DNA damage has been concerned with diazonium ions. We proposed a new bonding model and have established a variety of direct links between theory and experiment. Current studies of diazonium ions focus on the mechanisms of their SN chemistry.

The possibility of pyrimidine ring-opening during the dediazoniation of guaninediazonium ion has been one of the focal points of our research. We have succeeded in the demonstration that the theoretically postulated key intermediate can form all the known products of nitrosative guanosine deamination including the dG-to-dG cross-link. This research not only explains known chemistry, but instead it suggests that chemistry not previously considered may occur in vivo.

2. Polar Order in Crystalline Organic Molecular Materials

Methods: Chemical Synthesis, Crystallization, X-Ray Crystallography, Differential Scanning Calorimetry (DSC), NMR (Solution, Solid State), Raman Spectroscopy, Optical Spectroscopy (Solution, Solid State), Halogen Bonding, Arene-Arene Bonding, van der Waals Bonding, Ab Initio Theory, DFT Theory, Structure Analysis (as in "thinking about structure")

The rational design of polar crystals remains a grand challenge and for a long time it was believed that the parallel alignment of polar molecules in crystals cannot be achieved at all. With a combination of theoretical, mathematical, computational and experimental chemistry, we have achieved the fabrication of several classes of near-perfectly - our first success is shown, the (MeO,Br)-azine - and perfectly aligned materials. Of the 14 prototypes (by 03/19/04), 7 are near-perfectly and 7 are perfectly parallel aligned!

Among other classes of materials, push-push, pull-pull, and push-pull azines X-Ph-CR=N-N=CR-Ph-Y and dienes X-Ph-CR=CH-CH=CR-Ph-Y are being studied to understand and refine the design concepts. Entirely new structured, polar, and anisotropic materials are now conceivable and are being explored.

3. Chemistry in Interstellar and Intergalactic Media

Methods: Ab Initio Theory, Ion-Molecule Chemistry, Mass Spectrometry, Statistics, Collision Kinetics, Astrobiology.

The universe is 13.7 billion years old, it is flat, 4 percent of its energy is condensed into matter as we know it ("normal" matter made out of "normal" energy), 23 percent of its energy is condensed into "dark matter" (particular matter we don't know yet which is made of "normal" energy), and 73 percent is dark energy (an energy form we don't know). After "The Big Bang" and subsequent inflation, the universal expansion was slowed by gravitation, and it is the dark energy that started, some 5 billion years ago, to again accelerate the universal expansion toward the "The Big Rip". All this is known, not merely hypothesized, because of measured data from the Wilkinson Microwave Anisotropy Probe (WMAP, unevenness in the 2K background radiation) and the Sloan Digital Sky Survey (SDSS, spacial distribution of 1 million galaxies).

Of the 4 percent of normal matter, we "see" only a rather small part: Light itself, the matter in stars, and the interstellar and intergalactic stuff that interacts with light in some way (reflect, absorb, emit, redirect). The locations of hydrogen clouds are being determined via Lyman a-forest analysis. It is already clear that there is a lot more invisible matter than there is visible matter and most chemistry in the cosmos occurs in the dark and unobserved in interstellar and intergalactic clouds.

It is our hypothesis that the DNA bases can be synthesized in the interstellar medium from the materials present in any galaxy. Hence, we think that life literally everywhere can be DNA based and, with the principle of parsimony, we believe that it is. We employ scientific methods to provide evidence for our beliefs or to refute them, for now, at least for our milky way galaxy.

4. Nucleophilic Additions to Heterocumulenes

Theoretical Methods: Microsolvation & Catalysis, Hydrogen Bonding, van der Waals Bonding, Ab Initio Theory, DFT Theory

Nucleophilic additions to heterocumulenes are central in many important areas and the hydrolysis of carbon dioxide is by far the most important reaction in this group (enzymatic reaction in metabolism, greenhouse gas capture). The hydrolysis of carbodiimides is important in synthesis and in industrial applications. Additions to ketenes and ketenimines fall into this category as well and their chemistry has been well explored.

We are interested in carbon dioxide, O=C=O, and its diimide, HN=C=NH, and we are motived by a desire to learn about the latter. The HN=C=N- group may play a role in nucleophilic additions to guanine derivatives. Most recently, we explored the synergism of catalysis and reaction center rehybridization in nucleophilic additions to carbodiimide with one, two, and three water molecules. The placement of the third water makes all the difference for the catalysis of the hydrolysis of carbodiimide. Quantum-mechanical calculations show that micro-solvation by a spectator molecule is more important than increasing the size of the proton-transfer ring.

5. Electronic Structure Theory: Potential Energy Surfaces and Dynamics

Merriam-Webster defines (14th century) ... 2a: a sudden, radical, or complete change b: a fundamental change in political organization; especially: the overthrow or renunciation of one government or ruler and the substitution of another by the governed c: activity or movement designed to effect fundamental changes in the socioeconomic situation d: a fundamental change in the way of thinking about or visualizing something: a change of paradigm e: a changeover in use or preference especially in technology .

Moore's law describes the computer revolution and the consequential and directly associated information access revolution. Possession, generation, and analysis of and access to data has become one of the essential aspects of being "free". We use this new degree of freedom to the fullest in research and education.

We focus on the applications of ab initio methods (Gaussian 03) achieving high accuracy with perturbational approaches (MP%, G1, G2, G3, G2MP2), variational CI methods (MCSCF, QCI, CC), and density functional theory (DFT). Molecular mechanics is used in molecular dynamics studies (AMBER, AUTODOCK). Our interest in fundamental bonding theory concerns aspects of dative bonding and analyses of energy distributions in molecules via fragment transfer energy analysis. We emphasize electron and spin density analysis in studies of bonding and analyze electronic structures in a variety of ways (multipole distributions with charges, dipole, and quadrupoles, polarizabilities, hyperpolarizabilities, ...).

Most recently, we have been studying the mechanisms of nucleophilic substitution at heteroaromatic substrates. We have proposed that such reactions involve bimolecular processes with transition state structures of the type shown on the right for the reaction of water with benzenediazonium ion.

In another line of research, we are interested in trying to understand how reactions in DNA and synthetic oligonucleotides are affected by their highly anisotropic environment. Specifically, we are interested in understanding just how the mechanism of oxanine formation in DNA differs from the reaction in homogeneous solution. Experimentally, we are determining oxanine isotropomer ratios obtained in (18O)water and by deamination of [6-18O]dG-containing synthetic oligonucleotides.

Click on the picture on the right to animate the DNA decamer as AVI video (5.7 MB).

6. Chemistry is in the News: Collaboration, Communication, Science Community and Society

Methods: Scientific Literacy, Media Literacy, Learning Theory, Constructivist Theory, Research on Peer Review, Assessment, Information Technology, Computer-Assisted Collaboration, Computer-Mediated Communication, Scientific Writing, Philosophy of Science.

Bronowski pointed out the private (independence, originality) and public (truthfulness, dissent) components of science and the need for both in the scientific society. Ziman writes that Science is Public Knowledge and that science stands in the region where the intellectual, the psychological and the sociological coordinate axes intersect. Habermas talks about the systems sphere (science, technology, corporate capitalism, bureaucracy) and the cultural sphere (private and public life, morality, culture) and the need to harmonize progress in science and technology with the cultural sphere. Successful human evolution as a collective learning device requires effort to discuss and bring about consensus about the systems sphere in the cultural sphere to guarantee democracy.

University science education largely focuses on disciplinary skill training. Making the connections to the students (psychology) and to needs of the public (sociology) either is neglected or not attempted at all. Yet, it is the complexity that comes from these connections that brings the subject to life, makes students better learners, and provides them with the abilities to become life-long learners and free citizens in a democratic society.

The Chemistry is in the News project enables students to see the connections, to understand science and its role in society, and to use this knowledge in the evaluation and in making judgements about choices presented in everyday life.