People & Research

Richard S. Givens

Emeritus Professor

Richard S. Givens photo

1251 Wescoe Hall Drive
Malott Hall, Room 5010
University of Kansas
Lawrence, KS 66045

Phone: (785) 864-3846

Fax: (785) 864-5396


Academic Degrees

  • B.S., 1962, Marietta College
  • Ph.D., 1966, University of Wisconsin at Madison
  • National Institutes of Health Postdoctoral Fellow, 1966-1967, Iowa State University

Areas of Specialization

Organic Chemistry: Mechanistic Organic Photochemistry and Catalytic Oxidation Reactions

Research Interests

Givens Research Group Page

Photochemical Reactions and Mechanistic Investigations of “Caged” Compounds
In our quest to discover fundamentally new light activated chemical reactions, we have uncovered very useful methods for the release of reagents and biological substrates. We have applied these reactions in such diverse fields as organic synthesis, physiology, and combinatorial chemistry. Photoremovable protecting groups or “caged” compounds, as the derivatives have become to be known, use light to break chemical bonds and essentially instantaneously release a reagent or biological substrate. Furthermore, since light can be focused on specific, minute locations with a predetermined intensity, light-activated processes provide exquisite control in triggering initiators or agonists for chemical or biological processes.
[For a recent monograph on Caged Compounds, see:]

As an example, the release of neurotransmitters in neuron cell preparations stimulates the cell or its components within a few milliseconds or less. Thresholds for the activation and effects of agonists and antagonists can be explored using caged glutamate. Correctly organized neuronal networks and delicately balanced synaptic excitatory-inhibitory interactions are fundamental for normal brain function. In one of our collaborations, the Kandler group investigates the developmental mechanisms by which converging excitatory (glutamatergic) and inhibitory (GABA/glycinergic) neuronal networks become spatially organized and functionally fine tuned. An example of this plasticity of neonatal neuronal connections has been registered in the time-controlled photorelease of glutamic acid (Glu) by photolysis of our caged pHP Glu. The Kandler group addresses these issues in a study of an inhibitory sound localization circuit in the mammalian brainstem. They recently used our pHP glutamate to functionally map the development of inhibitory connectivity patterns and thereby demonstrated that functional synapse elimination and strengthening are important events in the establishment of precisely organized inhibitory circuits (Kim and Kandler, 2003).


The rules and mechanism that govern the reorganization of inhibitory circuits in the auditory system or any other brain region are the research focus of many laboratories including Kandler’s. Although these mechanisms are currently poorly understood, it is quite intriguing that synaptic refinement takes place during the developmental stage in which individual inhibitory synapses not only release glycine but also release GABA (Nabekura et al., 2004) and while GABA and glycine are excitatory and increase postsynaptic [Ca+2]i. More detailed insight of the cellular consequences of these temporary properties of immature inhibitory synapses and their role on synaptic plasticity will be key to understand how the brain becomes wired up during development.


Fig. 1. Developmental refinement of the MNTB-LSO connections as determined by functional mapping with pHP glutamate. (a,b) shows an input map in a 3-day old (P) rat and (c,d) in a P14 rat. (a) Location of uncaging sites that elicit (colored circles) or do not elicit (open circles) synaptic responses in a LSO neuron. Uncaging sites are overlaid onto a video picture of the MNTB (outlined in black). Responsive sites are color coded according to peak amplitudes of postsynaptic LSO responses. Examples of synaptic responses elicited from three locations (marked with x) are illustrated in the lower traces. (b) Interpolated 3-D plot of input areas. The size of the MNTB is scaled to match the size at P14 (d). (c, d) MNTB-LSO input map form a P14 rat. Scale bars (a) and (c) are 100 µm. From Kim and Kandler, 2003 Nature Neuroscience, 6, 282-290.

Photostimulated Cross Linking of Type II collagen
Another collaborative project has addressed the difficulty in repairing torn ligaments and other collagenous materials. Professor George Timberlake, Department of Ophthalmology at the KU Medical Center, has worked with our group in the design and development of a photochemical method for closing incisions and wounds in the eye. A new tethered photoactive reagent has been synthesized that can be applied to collagen surfaces and irradiated for a few minutes to form new bonds that are often as strong as a nylon suture. This new material is being refined so that it can be applied to bind proteins to other materials or surfaces. The photochemical application involves the formation of reactive ketenes which have been tethered through a polyethylene glycol unit or a PAMAM dendrimer. The ketenes react with lysyl amino groups on collagen and with other reactive nucleophiles to form new covalent bonds, e.g. peptide linkages, thus fastening the two materials together. Figure 2 illustrates the sequence for the PAMAM derivatives as shown here.


Synthetic and Mechanistic Studies of Cobalt-catalyzed Oxidations of Hydrocarbons
The focus of our research program on the oxidation of hydrocarbons has been the discovery of new mild, environmentally beneficial methods to oxidize hydrocarbons with a Co(II) catalyst using air in a high pressure CO2–acetic acid environment. Substrates such as xylene, ethylbenzene, and cyclohexane, can be oxidized using O2 or air and a co-catalyst with Co(II) to form terephthalic acid (90% yield), acetophenone (80%) and adipic acid (40%), respectively. The mechanism of this “green chemistry” oxidation reaction is being examined using our ReactIR to follow the time-dependent change in the infrared spectra of the reactants, intermediates, and products.
[For further information, see Timberlake, G. T.; Yousef, A. L., Chiles, S. R.; Moses, R. A.; Givens, R. S., (2005) Photochem. Photobiol., 81, 1180–1185, below.]


[For further information on the Center for Environmental Beneficial Catalysis (CEBC), see the website:]

Selected publications (click for .pdf copy)

83. Rajesh, C. S.; Givens, R.; Wirz, J. Kinetics and Mechanism of Phosphate Photorelease from Benzoin Diethyl Phosphate: Evidence for Adiabatic Fission to an α-Keto Cation in the Triplet State, (2000) J. Am. Chem. Soc., 122, 611–618.

84. Givens, R. S.; Weber, J. F. W.; Conrad II, P. G.; Orosz, G.; Donahue, S. L.; Thayer, S. A New Phototriggers 9: p-Hydroxyphenacyl as a C-Terminus Photoremovable Protecting Group for Oligopeptides, (2000) J. Am. Chem. Soc.,122, 2687–2697.

85. Geibel, S.; Barth, A.; Amslinger, S.; Jung, A. H.; Burzik, C.; Clarke, R. J.; Givens, R.; Fendler, K. P3-[2-(4-hydroxyphenyl)-2-oxo]ethyl ATP for the rapid activation of the Na+,K+-ATPase. (2000) Biophys. J., 79(3), 1346–1357.

86. Conrad II, P. G.; Givens, R. S.; Weber, J. F. W.; Kandler, K. New Phototriggers 10: Extending the p,p* Absorption to Release Peptides in Biological Media, (2000) Org. Lett. 2, 1545–1547.

87. Conrad II, P. G.; Givens, R. S.; Hellrung, B.; Rajesh, C. S., Ramseier, M.; Wirz, J. p-Hydroxyphenacyl Phototriggers: The Reactive Excited State of Phosphate Photorelease, (2000) J. Am. Chem. Soc., 122, 9346–9347.

88. Zou, K.; Miller, T. W.; Givens, R. S.; Bayley, H. Caged Thiophphotyrosine Peptides, (2001) Angew. Chem. Int. Ed, 40, 3049–3051.

89. Chimilio, L. A.; Givens, R. S. Solvolytic Behavior and Photorearrangement of p-Hydroxyphenacyl Sulfonates: A Comparative Study, Org. Letts. (to be submitted).

89. Zou, K.; Cheley, S.; Givens, R. S.; Bayley, H. Catalytic subunit of protein kinase A caged at the activating phosphothreonine, (2002) J. Amer. Chem. Soc., 124, 8220–8229.

90. Timberlake, G. T.; Reddy, G. K.; Steno-Bittel, L.; Weber, J. J. W.; Amslinger, S.; Givens, R. S. Photoactivated coumaryl-diazopyruvate fluorescent label for amine functional groups of tissues containing type I collagen. (2002) Photochem. Photobiol., 76(5), 473–479.

91. Givens, R. S.; Lee, J.-I. The p-Hydroxyphenacyl Photoremovable Protecting Group, (2003) J.>Photoscience, 10, 37–48.

92. Givens, R. S.; Conrad, P. G. II; Yousef, A. L.; Lee, J.-I., Photoremovable Protecting Groups in CRC Handbook of Organic Photochemistry and Photobiology, (2003) 2nd Edition, W. M. Horspool, ed., Ch. 69, pp 69.1–69.46.

93. Sul, J-Y; Orosz, G.; Givens, R. S.; Haydon, P. G. Astrocytic Circuits in the Hippocampus, (2004) Neuron Glia Biology, 1, 3–10. (94. Cited in Scientific American in March, 2004.)

94. Zou, X; Archibald, S.J.; Hassan, A. M., Givens, R. S.; McCasland, A. K.; Busch, D. H. Toward the soil poultice and a new separation methodology: Rebinding of macrocycle metal complexes to molecularly imprinted polymers specifically templated via hydrogen bonding, 2003, in revision.

95. Sul, J-Y; Orosz, G.; Givens, R. S.; Haydon, P. G. Astrocytic Circuits in the Hippocampus, (2004) Neuron Glia Biology, 1, 3–10. (94. Cited in Scientific American in March, 2004.)

96. Hasan, M. M.; Zhang, C.; Lee, J.-I.; Bushan, K. M.; McCasland, A.; Givens, R. S.; Busch, D. H. Dynamics of switch-binding by a linear ligand that transforms to a macrocycle upon chelation to a metal ion: synthesis, kinetics, and equilibria, EMSP Symposium, ACS Meeting, New York, NY, 2003, 0000 (in press).

97. Givens, R. S.; Goeldner, M. (co-editors) Dynamic Studies in Biology: Phototriggers, Photoswitches, and Caged Biomolecules, (2005) J. Wiley, and Sons, (monograph). (95. Reviewed in J. Am. Chem. Soc.)

98. Givens, R. S.; Yousef, A. p-Hydroxyphenacyl: A Photoremovable Protecting Group for Caging Bioactive Substrates (Ch. Ic) in Dynamic Studies in Biology: Phototriggers, Photoswitches, and Caged Biomolecules (2005) J. Wiley, and Sons, pp. 55–75. (Chapter 1.2)

99. Givens, R. S.; Lee, J.-I.; Kotala, M. Mechanistic overview of phototriggers and cage release (Ch. 2) in Dynamic Studies in Biology: Phototriggers, Photoswitches, and Caged Biomolecules (2005) J. Wiley, and Sons, pp. 95–12(Chapter 2).

100. Zuo, X.; Mosha, D.; Hassan, M. M.; Givens, R. S.; Busch, D. H. A novel methodology for metal ion separation based on molecularly imprinting. (2004) Preprints of Extended Abstracts presented at the ACS National Meeting, American Chemical Society, Division of Environmental Chemistry, 44(1), 471–473.

101. Zou, X.; Mosha, D.; Archibald, S.J.; McCasland, A.K.; Hassan, A. M.; Givens, R. S.; Busch, D. H. Toward the Soil Poultice and a New Separations Methodology: Rebinding of Macrocyclic Metal Complexes to Molecularly Imprinted Polymers Specifically Templated via Non-covalent Interactions, (2005) Journal of Coordination Chemistry, 58, 21–39.

102. Timberlake, G. T.; Yousef, A. L., Chiles, S. R.; Moses, R. A.; Givens, R. S. Bonding Corneal Tissue: Applications of photoactivated diazopyruvoyl crosslinking agent, (2005) Photochem. Photobiol., 81, 1180–1185.

103. Givens, R.S., Yousef, A. L.; Yang, S., Timberlake; G. T., Collagen Cross Linking Agents: Design and Development of a Multifunctional Cross Linker, Photochemistry and Photobiology, (2008), 84: 185–192.

104. Conrad, P. II; Chavli, R. V.; Givens, R. S. Caged substrates applied to high content screening: An introduction with an eye to the future in “High Content Screening: A Powerful Approach in Systems Cell Biology and Drug Discovery”, Methods in Molecular Biology, High Content Screening (2007) Kenneth A Giuliano, Jeffrey Haskins, and D. Lans Taylor, ed., pp. 253-265.

105. Givens, R. S.; Heger, D., Hellrung, B.; Kamdzhilov, Y.; Mac, M.; Conrad, P. G.; Cope, E.; Lee, J. I.; Mata-Segreda, J. F.; Schowen, R. L.; Wirz, J.; The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds Is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical, J. Am. Chem. Soc., (2008), vol. 130/2008, no. 11, pp. 3307-3309.

106. Stensrud, K. F.; Heger, D.;Sebej, P.;Wirz, J.;Givens, R. S.; Fluorinated photoremovable protecting groups: the influence of fluoro substituents on the photo-Favorskii rearrangement. Photochemical & Photobiological Sciences, ( 2008), vol. 7, no. 5, pp. 614 - 624.

107. Stensrud, K. F.;Adam, P. R.;La Mar, C. D.;Olive, A. J.;Lushington, G. H.;Sudharsan, R.;Shelton, N. L.;Givens, R. S.;Picking, W. L.;Picking, W. D., Deoxycholate Interacts with IpaD of Shigella flexneri in Inducing the Recruitment of IpaB to the Type III Secretion Apparatus Needle Tip, The Journal of Biological Chemistry, (2008), vol. 283, no.27.

108. Stensrud, K. F.; Noh, J.; Kandler, K.;Wirz, J.; Heger, D.; Givens, R. L.;. Competing Pathways in the Photo-Favorskii Rearrangement and Release of Esters: Studies on Fluorinated p-Hydroxyphenacyl-Caged GABA and Glutamate Phototriggers.Journal of Organic Chemistry, ( 2009), vol. 74, no. 15, pp. 5219-5227.

109. Sebej, Peter; Lim, Bum Hee; Park, Bong Ser; Givens, Richard S.; Klan, Petr. The Power of Solvent in Altering the Course of Photorearrangements. Org. Lett. (2011), 13(4), 644-647.

110. Marek Remeš, Jana Roithová, Detlef Schröder, Elizabeth Cope, Chamani Perera, Sanjeewa N. Senadheera, Kenneth Stensrud, Chi-cheng Ma, and Richard S. Givens. Gas-phase Fragmentation of Deprotonated p-Hydroxyphenacyl Derivatives. J. Org. Chem. (2011) 76 , 2180-2186.

111. Richard S. Givens; Kenneth Stensrud; Peter G. Conrad, II.; Abraham L. Yousef; Chamani Perera; Sanjeewa N. Senadheera, Dominik Heger; Jakob Wirz p-Hydroxyphenacyl Photoremovable Protecting Groups: Robust Photochemistry Despite Substituent Diversity. Can. J. Chem. (2011) 89, 364-384.

112. Karl Kandler, Tuan Nguyen, Jihyun Noh and Richard S. Givens, An Optical Fiber-Based Uncaging System. Ch 41, 000, in “Imaging in Neuroscience: A Laboratory Manual” (F. Helmche, A. Konnerth Ed.) Cold Spring Harbor Laboratory press (May, 2011) in press.

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