José M. Rivera

Jose M. Rivera

Associate Professor
Phone: 787-764-0000 ext. 2906
Fax: 787 756 8242

External Lab Web Page


Ph.D. Massachusetts Institute of Technology 2000
NIH Postdoctoral Fellow, The Scripps Research Institute 2000 – 2002

Research Interests

Supramolecular chemistry, molecular recognition, organic synthesis, nanotechnology, bioorganic chemistry, medicinal chemistry.

Research Focus

Our group focuses on using supramolecular chemistry as a tool for solving problems in biomedicine.

Our research interests are focused primarily on supramolecular chemistry and how it can be used to solve problems to improve our quality of life. Supramolecular chemistry has been broadly defined as the “chemistry beyond the molecule” and it deals primarily with the construction and study of architectures made by multiple molecules held together by non-covalent (or reversible covalent) interactions. Our particular long-term goal is to develop a variety of complex self-assembled multi-functional nanostructures to be used in biomedical applications.

Our basic strategy relies on the use of guanine-based recognition motifs that are relatively easy to make and offer robust and reliable self-recognition properties in a wide variety of environments (i.e. organic and aqueous media). Guanine (G) is a naturally occurring recognition motif well known for its ability to pair with cytosine in both DNA and RNA structures. Guanine is also self-complementary, which allows it to form planar cyclic tetrameric structures that further associate into coaxial stacks that are collectively known as G-quadruplexes (GQs). GQs are formed not just by individual guanine subunits but also by G-rich oligonucleotides. Quadruplex-DNA (QDNA) is the subject of many biological studies because of its putative role in telomere function and the regulation of oncogenes among others. GQs have also become particularly useful in the construction of sensors for a wide variety of analytes such as cations, nucleic acids and proteins as well as in the construction of nanomachines.

We are primarily focused on determining correlations between the molecular structure of various 8-aryl- and 8-heteroaryl-2’-deoxyguanosine (8ArGs and 8HetGs) derivatives and their supramolecular behavior. In particular, we aim to modulate the supramolecular properties such as molecularity, fidelity and stability of the resulting GQs. We are concomitantly applying such fundamental knowledge in the elaboration of:

(a)Quadruplex-DNA (QDNA) binders that can recognize QDNA with good affinity and selectivity. Such compounds may find uses in the development of anti-cancer drugs and probes for cellular biology studies.(b)Ionophores that can recognize a wide variety of cations with good selectivity and transport them across liquid membranes. Such compounds may find uses in the development of cation selective sensors and in environmental remediation strategies.

(c)Dendrimers are highly branched macromolecules that have found uses in many areas such as catalysis, small molecule encapsulation, therapeutics, etc. We are particularly interested in using self-assembled dendrimers for targeted drug-delivery applications and also as probes for cellular biology studies.

(d)Active nanostructures that can be assembled and disassembled at will by using chemical, electrochemical or photonic stimuli. We also incorporate dynamic covalent bonds that allow us to combine the advantages of design and selection in the construction of complex architectures. Of particular interest to us are systems that catalyze their own formation under particular selective pressures. This should enable the chemical evolution of more effective nanostructures that can be used to solve a wide variety of biomedical problems.

Selected Recent Publications

García-Arriaga, M.; Hobley, G.; Rivera, J. M. “Isostructural Self-Assembly of 2'-Deoxyguanosine Derivatives in Aqueous and Organic Media” J. Am. Chem. Soc. (2008) ASAP [DOI: 10.1021/ja8039019].

Hobley, G.; Gubala, V.; Rivera-Sánchez, M.C.; Rivera, J. M. “Synthesis of 8-Heteroaryl-2-deoxyguanosine Derivatives” Synlett (2008) 1510-1514 [DOI: 10.1055/s-2007-1077795].

Betancourt, J. E.; Rivera, J. M. “Hexadecameric Self-Assembled Dendrimers Built from 2'- Deoxyguanosine Derivatives” Org. Lett. (2008) 10, 2287-2290 [DOI: 10.1021/ol800701j].

Gubala, V.; Rivera-Sánchez, M.C.; Hobley, G.; Rivera, J.M. “Synthesis and impact on G-quadruplex formation of 8-aryl- and 8-heteroaryl-2'-deoxyguanosine derivatives”. Nucleic Acids Symp Ser, 51, 39-40 (2007) [DOI:10.1093/nass/nrm020].

Gubala, V.; De Jesús, D.; Rivera, J. M. “Self-assembled Ionophores Based on 8-Phenyl-2'-deoxyguanosine Analogues” Tetrahedron Lett. 47, 1413-1416 (2006).

Gubala, V.; Betancourt, J. E.; Rivera, J. M. “Expanding the Hoogsteen Edge of 2’-Deoxyguanosine: Consequences for G-Quadruplex Formation” Org. Lett. 6, 4735-4738 (2004).

Rivera, J. M., Martín, T. & Rebek, J., Jr. “Chiral Softballs: Synthesis and Molecular Recognition Properties” J. Am. Chem. Soc., 123, 5213-5220 (2001).

Rivera, J. M. & Rebek, J., Jr. “Chiral Space in a Unimolecular Capsule” J. Am. Chem. Soc. 122, 7811-7812 (2000).

Rivera, J. M.; Craig, S. L.; Martín, T.; Rebek, J., Jr. “Chiral Guests and their Ghosts in Reversibly-Assembled Hosts” Angew. Chem., Int. Ed. 39, 2130-2132 (2000).

Schalley, C. A.; Rivera, J. M.; Martín, T.; Santamaría, J.; Siuzdak, G.; Rebek, J., Jr. “Structural Examination of Supramolecular Architectures by Electrospray Ionization MS” Eur. J. Org. Chem., 1325-1331 (1999).

Rivera, J. M.; Martín, T.; Rebek, J., Jr. “Chiral Spaces: Dissymmetric Capsules through Self-Assembly” Science 279, 1021-1023 (1998).

Rivera, J. M.; Martín, T.; Rebek, J., Jr. “Structural Rules Governing Self-Assembly Emerge from New Molecular Capsules” J. Am. Chem. Soc. 120, 819-820 (1998).