AsianScientist (Dec. 30, 2015) – In biology, form and function are inseparable. Molecules of identical chemical makeup can bend, twist and rotate into a variety of different conformations. This affects their physical interactions with other molecules, and determines how accessible their reactive groups are to enzymes, the proteins that catalyse chemical reactions essential to life.
For instance, our basic senses—sight, smell, sound, taste and touch—depend on cascading signals initiated by the docking of appropriately-shaped molecules onto receptor proteins.
As molecules are tiny—a raindrop contains about one billion billion (1018) water molecules—chemists have developed ingenious techniques to determine their shape. They bombard molecules with electron beams, magnetic fields, and just about every wavelength along the electromagnetic radiation spectrum from everyday radio waves to biologically-hazardous gamma rays. The molecule’s response to these perturbations offers insights into its structure.
Huang Hsing Hua, professor emeritus of chemistry at the National University of Singapore (NUS), is one such molecular detective. A physical organic chemist, he has spent his career developing methods to reveal the shape of organic molecules, and thus better understand the mechanisms behind the reactions they participate in.
Science on a shoestring
Professor Huang came to Singapore from Malaysia in 1952 to study chemistry at the University of Malaya (UM). After doctoral studies at Oxford University, he returned to Singapore in 1959 to work as a lecturer.
At the time, many university faculty and staff had left for Kuala Lumpur, where another UM campus was being established.
“We were left with only a skeleton staff in Singapore,” he recalls.
Given these meagre resources, Professor Huang decided to revisit a research area from his master’s programme at UM. This involved using dipole moments to deduce the shape of organic molecules.
Chemical bonds—in essence, electrostatic attractions between atoms—hold molecules together. In some molecules, these bonds are polar, meaning that there is a separation of positive and negative electric charges within the bond, known as a dipole.
A water molecule (H2O), for example, is polar because its electronegative oxygen atom attracts negative charge away from its two hydrogen atoms. The dipole moment is a measure of polarity or the degree of charge separation, and can provide information about the position of atoms around the bond.
As research funds were low in pre-independence Singapore, UM was focussed mainly on teaching. So Professor Huang, in keeping with the resourcefulness of the times, used a dipolemeter built from scratch by his supervisor. It was made out of inexpensive radio components: oscillators that emitted radio waves at fixed and variable frequencies, a high-precision condenser (a glass tubing that cools hot gas into its liquid state), as well as a cell made by a local glass-blower.
In addition to this improvised equipment, Professor Huang also used a simple but novel method of synthesis to create new organic molecules—derivatives of ethane (C2H6)—that would serve as his subjects for study. He designed the molecules to have two polar symmetrical halves connected by a bond between the two carbon atoms. Because the two halves rotate around the carbon-carbon bond, the molecules cycle through several different conformations and energy states.
By measuring the various dipole moments Professor Huang could work out the angle of rotation, and thus deduce the molecule’s conformation, along with its potential reaction mechanisms.
Although Professor Huang worked with synthetic organic molecules that do not exist in nature, this technique could also be broadly applied to other naturally-occurring molecules that are soluble in non-polar solvents such as benzene.
Professor Huang’s molecular-detective work—first on dipole moments, then later on other analytical techniques such as infrared spectroscopy, ultraviolet photoelectron spectroscopy, and X-ray crystallography—has contributed to the theoretical understanding that chemists now have of molecular conformation and reactivity.
This knowledge underpins modern advances in applied fields such as molecular pharmacology. This includes the design of effective drugs, which requires detailed knowledge of how molecules interact in three-dimensional space.
For his scientific contributions to the field of physical organic chemistry, Professor Huang received the National Science Award in 1994 from the National Science and Technology Board.
Shaping a university
Funding for research remained extremely limited in the 1960s-70s, and many would-be academics turned instead to careers in the foreign service or in politics. During those years the research budget for the entire university was a few hundred thousand dollars.
“You can imagine how much each department got,” Professor Huang says.
The situation improved in the 1980s, when the government began to place more importance on research and innovation as an economic driver. The Science Council started to accept applications for research funding. Meanwhile, money began to flow in from unconventional sources such as Singapore Pools, the state-owned lottery firm.
In 1981, the newly-formed NUS appointed Professor Huang as deputy vice-chancellor. He was charged with promoting interdisciplinary research, which integrates concepts, techniques and data from multiple fields of study to solve complex problems. Dealing with outbreaks of infectious diseases such as influenza and Ebola, for example, requires cooperation between medical professionals, biologists, epidemiologists and public health authorities.
“No one can predict the issues that science and society will consider most pressing in the decades to come,” says Professor Huang. “The integration of research and education through interdisciplinary training prepares a workforce to undertake scientific challenges in innovative ways.”
The value of interdisciplinary collaboration is well accepted today. But researchers at the time felt that they could more easily make advances and achieve recognition within their own fields, and were thus reluctant to engage with those outside.
“Nevertheless, it was important because real life problems or issues require for their solution a combined attack using knowledge from different disciplines,” says Professor Huang.
To encourage them to venture outside the confines of their own fields of expertise, Professor Huang held formal seminars and informal conversations with NUS staff. From his tenure onwards, NUS started to look favourably on funding requests for collaborative projects, and hosted interdisciplinary conferences in a variety of areas, including environmental science, computer science, mathematics and biomedical engineering.
Professor Huang’s own field of research had already matured by the time he became deputy vice-chancellor. Another of his roles, then, was to identify new research niches in which Singapore could develop an expertise. He recruited talented faculty members in burgeoning fields such as nanotechnology and surface science.
Surface science, in particular, was where Professor Huang saw opportunities for interdisciplinary collaboration. The field deals with the unique chemical and physical properties occurring at the interface of two phases, such as solid-liquid or solid-air, and has applications in areas such as semiconductor manufacturing, industrial catalysis and fuel cell production. Under his leadership, NUS established a surface science laboratory in its department of physics, which allowed for collaborative work with its department of chemical engineering.
This laboratory was an early iteration of the many NUS-founded research institutes that are multidisciplinary in nature today, including the Institute of Molecular and Cell Biology (IMCB), the Institute of Materials Research and Engineering (IMRE), and the Institute of Systems Science (ISS).
As the research environment at NUS improved, the university started to attract talented students and post-doctoral researchers from around the world.
“By the time I retired [in 1997] NUS had started to make a name,” says Professor Huang.
In recognition of his contributions to science and to the university, Professor Huang received the NUS Distinguished Science Alumni Award in 1999.
Going beyond head knowledge
Professor Huang is optimistic about the future of NUS under its current administration, although he is unsure when it will achieve its ultimate goal of producing a Nobel laureate.
“Singapore has been very successful in producing people with book knowledge,” he says. “But beyond that you need people who can think originally to really make a huge impact.”
Since his retirement in 1997, Professor Huang has dedicated a large portion of his time to studying the Bible. But that’s not enough. With religion, as with science, he believes in the importance of linking theory with practice, of translating book knowledge into action. For him, part of the answer lies in volunteering at St Andrew’s Community Hospital, where he spends time talking with patients and keeping them company.
This feature is part of a series of 25 profiles, first published as Singapore’s Scientific Pioneers. Click here to read the rest of the articles in this series.
———
Copyright: Asian Scientist Magazine; Photo: Cyril Ng.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
